Feature

BERLIN — To date, mRNA vaccines have had their largest global presence in combating the COVID-19 pandemic. Intensive research is underway on many other potential applications for this vaccine technology, which suggests a promising future. Martina Prelog, MD, a pediatric and adolescent medicine specialist at the University Hospital of Würzburg in Germany, reported on the principles, research status, and perspectives for these vaccines at the 25th Travel and Health Forum of the Center for Travel Medicine in Berlin.

To understand the future, the immunologist first examined the past. “The induction of cellular and humoral immune responses by externally injected mRNA was discovered in the 1990s,” she said.
 

Instability Challenge

Significant hurdles in mRNA vaccinations included the instability of mRNA and the immune system’s ability to identify foreign mRNA as a threat and destroy mRNA fragments. “The breakthrough toward vaccination came through Dr. Katalin Karikó, who, along with Dr. Drew Weissman, both of the University of Pennsylvania School of Medicine, discovered in 2005 that modifications of mRNA (replacing the nucleoside uridine with pseudouridine) enable better stability of mRNA, reduced immunogenicity, and higher translational capacity at the ribosomes,” said Dr. Prelog.

With this discovery, the two researchers paved the way for the development of mRNA vaccines against COVID-19 and other diseases. They were awarded the Nobel Prize in medicine for their discovery last year.
 

Improved Scalability

“Since 2009, mRNA vaccines have been studied as a treatment option for cancer,” said Dr. Prelog. “Since 2012, they have been studied for the influenza virus and respiratory syncytial virus [RSV].” Consequently, several mRNA vaccines are currently in development or in approval studies. “The mRNA technology offers the advantage of quickly and flexibly responding to new variants of pathogens and the ability to scale up production when there is high demand for a particular vaccine.”

Different forms and designations of mRNA vaccines are used, depending on the application and desired effect, said Dr. Prelog.

In nucleoside-modified mRNA vaccines, modifications in the mRNA sequence enable the mRNA to remain in the body longer and to induce protein synthesis more effectively.

Lipid nanoparticle (LNP)–encapsulated mRNA vaccines protect the coding mRNA sequences against degradation by the body’s enzymes and facilitate the uptake of mRNA into cells, where it then triggers the production of the desired protein. In addition, LNPs are involved in cell stimulation and support the self-adjuvant effect of mRNA vaccines, thus eliminating the need for adjuvants.

Self-amplifying mRNA vaccines include a special mRNA that replicates itself in the cell and contains a sequence for RNA replicase, in addition to the coding sequence for the protein. This composition enables increased production of the target protein without the need for a high amount of external mRNA administration. Such vaccines could trigger a longer and stronger immune response because the immune system has more time to interact with the protein.
 

Cancer Immunotherapy

Dr. Prelog also discussed personalized vaccines for cancer immunotherapy. Personalized mRNA vaccines are tailored to the patient’s genetic characteristics and antigens. They could be used in cancer immunotherapy to activate the immune system selectively against tumor cells.

Multivalent mRNA vaccines contain mRNA that codes for multiple antigens rather than just one protein to generate an immune response. These vaccines could be particularly useful in fighting pathogens with variable or changing surface structures or in eliciting protection against multiple pathogens simultaneously.

The technology of mRNA-encoded antibodies involves introducing mRNA into the cell, which creates light and heavy chains of antibodies. This step leads to the formation of antibodies targeted against toxins (eg, diphtheria and tetanus), animal venoms, infectious agents, or tumor cells.
 

Genetic Engineering

Dr. Prelog also reviewed genetic engineering techniques. In regenerative therapy or protein replacement therapy, skin fibroblasts or other cells are transfected with mRNA to enable conversion into induced pluripotent stem cells. This approach avoids the risk for DNA integration into the genome and associated mutation risks.

Another approach is making post-transcriptional modifications through RNA interference. For example, RNA structures can be used to inhibit the translation of disease-causing proteins. This technique is currently being tested against HIV and tumors such as melanoma.

In addition, mRNA technologies can be combined with CRISPR/Cas9 technology (“gene scissors”) to influence the creation of gene products even more precisely. The advantage of this technique is that mRNA is only transiently expressed, thus preventing unwanted side effects. Furthermore, mRNA is translated directly in the cytoplasm, leading to a faster initiation of gene editing.

Of the numerous ongoing clinical mRNA vaccine studies, around 70% focus on infections, about 12% on cancer, and the rest on autoimmune diseases and neurodegenerative disorders, said Dr. Prelog.
 

Research in Infections

Research in the fields of infectious diseases and oncology is the most advanced: mRNA vaccines against influenza and RSV are already in advanced clinical trials, Dr. Prelog told this news organization.

“Conventional influenza vaccines contain immunogenic surface molecules against hemagglutinin and neuraminidase in various combinations of influenza strains A and B and are produced in egg or cell cultures,” she said. “This is a time-consuming manufacturing process that takes months and, particularly with the egg-based process, bears the risk of changing the vaccine strain.”

“Additionally, influenza viruses undergo antigenic shift and drift through recombination, thus requiring annual adjustments to the vaccines. Thus, these influenza vaccines often lose accuracy in targeting circulating seasonal influenza strains.”

Several mRNA vaccines being tested contain not only coding sequences against hemagglutinin and neuraminidase but also for structural proteins of influenza viruses. “These are more conserved and mutate less easily, meaning they could serve as the basis for universal pandemic influenza vaccines,” said Dr. Prelog.

An advantage of mRNA vaccines, she added, is the strong cellular immune response that they elicit. This response is intended to provide additional protection alongside specific antibodies. An mRNA vaccine with coding sequences for the pre-fusion protein of RSV is in phase 3 trials for approval for vaccination in patients aged 60 years and older. It shows high effectiveness even in older patients and those with comorbidities.
 

Elaborate Purification Process

Bacterial origin plasmid DNA is used to produce mRNA vaccines. The mRNA vaccines for COVID-19 raised concerns that production-related DNA residues could pose a safety risk and cause autoimmune diseases.

These vaccines “typically undergo a very elaborate purification process,” said Dr. Prelog. “This involves enzymatic digestion with DNase to fragment and deplete plasmid DNA, followed by purification using chromatography columns, so that no safety-relevant DNA fragments should remain afterward.”

Thus, the Paul-Ehrlich-Institut also pointed out the very small, fragmented plasmid DNA residues of bacterial origin in mRNA COVID-19 vaccines pose no risk, unlike residual DNA from animal cell culture might pose in other vaccines.
 

Prevention and Therapy

In addition to the numerous advantages of mRNA vaccines (such as rapid adaptability to new or mutated pathogens, scalability, rapid production capability, self-adjuvant effect, strong induction of cellular immune responses, and safety), there are also challenges in RNA technology as a preventive and therapeutic measure, according to Dr. Prelog.

“Stability and storability, as well as the costs of new vaccine developments, play a role, as do the long-term effects regarding the persistence of antibody and cellular responses,” she said. The COVID-19 mRNA vaccines, for example, showed a well-maintained cellular immune response despite a tendency toward a rapid decline in humoral immune response.

“The experience with COVID-19 mRNA vaccines and the new vaccine developments based on mRNA technology give hope for an efficient and safe preventive and therapeutic use, particularly in the fields of infectious diseases and oncology,” Dr. Prelog concluded.

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

BERLIN — To date, mRNA vaccines have had their largest global presence in combating the COVID-19 pandemic. Intensive research is underway on many other potential applications for this vaccine technology, which suggests a promising future. Martina Prelog, MD, a pediatric and adolescent medicine specialist at the University Hospital of Würzburg in Germany, reported on the principles, research status, and perspectives for these vaccines at the 25th Travel and Health Forum of the Center for Travel Medicine in Berlin.

To understand the future, the immunologist first examined the past. “The induction of cellular and humoral immune responses by externally injected mRNA was discovered in the 1990s,” she said.
 

Instability Challenge

Significant hurdles in mRNA vaccinations included the instability of mRNA and the immune system’s ability to identify foreign mRNA as a threat and destroy mRNA fragments. “The breakthrough toward vaccination came through Dr. Katalin Karikó, who, along with Dr. Drew Weissman, both of the University of Pennsylvania School of Medicine, discovered in 2005 that modifications of mRNA (replacing the nucleoside uridine with pseudouridine) enable better stability of mRNA, reduced immunogenicity, and higher translational capacity at the ribosomes,” said Dr. Prelog.

With this discovery, the two researchers paved the way for the development of mRNA vaccines against COVID-19 and other diseases. They were awarded the Nobel Prize in medicine for their discovery last year.
 

Improved Scalability

“Since 2009, mRNA vaccines have been studied as a treatment option for cancer,” said Dr. Prelog. “Since 2012, they have been studied for the influenza virus and respiratory syncytial virus [RSV].” Consequently, several mRNA vaccines are currently in development or in approval studies. “The mRNA technology offers the advantage of quickly and flexibly responding to new variants of pathogens and the ability to scale up production when there is high demand for a particular vaccine.”

Different forms and designations of mRNA vaccines are used, depending on the application and desired effect, said Dr. Prelog.

In nucleoside-modified mRNA vaccines, modifications in the mRNA sequence enable the mRNA to remain in the body longer and to induce protein synthesis more effectively.

Lipid nanoparticle (LNP)–encapsulated mRNA vaccines protect the coding mRNA sequences against degradation by the body’s enzymes and facilitate the uptake of mRNA into cells, where it then triggers the production of the desired protein. In addition, LNPs are involved in cell stimulation and support the self-adjuvant effect of mRNA vaccines, thus eliminating the need for adjuvants.

Self-amplifying mRNA vaccines include a special mRNA that replicates itself in the cell and contains a sequence for RNA replicase, in addition to the coding sequence for the protein. This composition enables increased production of the target protein without the need for a high amount of external mRNA administration. Such vaccines could trigger a longer and stronger immune response because the immune system has more time to interact with the protein.
 

Cancer Immunotherapy

Dr. Prelog also discussed personalized vaccines for cancer immunotherapy. Personalized mRNA vaccines are tailored to the patient’s genetic characteristics and antigens. They could be used in cancer immunotherapy to activate the immune system selectively against tumor cells.

Multivalent mRNA vaccines contain mRNA that codes for multiple antigens rather than just one protein to generate an immune response. These vaccines could be particularly useful in fighting pathogens with variable or changing surface structures or in eliciting protection against multiple pathogens simultaneously.

The technology of mRNA-encoded antibodies involves introducing mRNA into the cell, which creates light and heavy chains of antibodies. This step leads to the formation of antibodies targeted against toxins (eg, diphtheria and tetanus), animal venoms, infectious agents, or tumor cells.
 

Genetic Engineering

Dr. Prelog also reviewed genetic engineering techniques. In regenerative therapy or protein replacement therapy, skin fibroblasts or other cells are transfected with mRNA to enable conversion into induced pluripotent stem cells. This approach avoids the risk for DNA integration into the genome and associated mutation risks.

Another approach is making post-transcriptional modifications through RNA interference. For example, RNA structures can be used to inhibit the translation of disease-causing proteins. This technique is currently being tested against HIV and tumors such as melanoma.

In addition, mRNA technologies can be combined with CRISPR/Cas9 technology (“gene scissors”) to influence the creation of gene products even more precisely. The advantage of this technique is that mRNA is only transiently expressed, thus preventing unwanted side effects. Furthermore, mRNA is translated directly in the cytoplasm, leading to a faster initiation of gene editing.

Of the numerous ongoing clinical mRNA vaccine studies, around 70% focus on infections, about 12% on cancer, and the rest on autoimmune diseases and neurodegenerative disorders, said Dr. Prelog.
 

Research in Infections

Research in the fields of infectious diseases and oncology is the most advanced: mRNA vaccines against influenza and RSV are already in advanced clinical trials, Dr. Prelog told this news organization.

“Conventional influenza vaccines contain immunogenic surface molecules against hemagglutinin and neuraminidase in various combinations of influenza strains A and B and are produced in egg or cell cultures,” she said. “This is a time-consuming manufacturing process that takes months and, particularly with the egg-based process, bears the risk of changing the vaccine strain.”

“Additionally, influenza viruses undergo antigenic shift and drift through recombination, thus requiring annual adjustments to the vaccines. Thus, these influenza vaccines often lose accuracy in targeting circulating seasonal influenza strains.”

Several mRNA vaccines being tested contain not only coding sequences against hemagglutinin and neuraminidase but also for structural proteins of influenza viruses. “These are more conserved and mutate less easily, meaning they could serve as the basis for universal pandemic influenza vaccines,” said Dr. Prelog.

An advantage of mRNA vaccines, she added, is the strong cellular immune response that they elicit. This response is intended to provide additional protection alongside specific antibodies. An mRNA vaccine with coding sequences for the pre-fusion protein of RSV is in phase 3 trials for approval for vaccination in patients aged 60 years and older. It shows high effectiveness even in older patients and those with comorbidities.
 

Elaborate Purification Process

Bacterial origin plasmid DNA is used to produce mRNA vaccines. The mRNA vaccines for COVID-19 raised concerns that production-related DNA residues could pose a safety risk and cause autoimmune diseases.

These vaccines “typically undergo a very elaborate purification process,” said Dr. Prelog. “This involves enzymatic digestion with DNase to fragment and deplete plasmid DNA, followed by purification using chromatography columns, so that no safety-relevant DNA fragments should remain afterward.”

Thus, the Paul-Ehrlich-Institut also pointed out the very small, fragmented plasmid DNA residues of bacterial origin in mRNA COVID-19 vaccines pose no risk, unlike residual DNA from animal cell culture might pose in other vaccines.
 

Prevention and Therapy

In addition to the numerous advantages of mRNA vaccines (such as rapid adaptability to new or mutated pathogens, scalability, rapid production capability, self-adjuvant effect, strong induction of cellular immune responses, and safety), there are also challenges in RNA technology as a preventive and therapeutic measure, according to Dr. Prelog.

“Stability and storability, as well as the costs of new vaccine developments, play a role, as do the long-term effects regarding the persistence of antibody and cellular responses,” she said. The COVID-19 mRNA vaccines, for example, showed a well-maintained cellular immune response despite a tendency toward a rapid decline in humoral immune response.

“The experience with COVID-19 mRNA vaccines and the new vaccine developments based on mRNA technology give hope for an efficient and safe preventive and therapeutic use, particularly in the fields of infectious diseases and oncology,” Dr. Prelog concluded.

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

BERLIN — To date, mRNA vaccines have had their largest global presence in combating the COVID-19 pandemic. Intensive research is underway on many other potential applications for this vaccine technology, which suggests a promising future. Martina Prelog, MD, a pediatric and adolescent medicine specialist at the University Hospital of Würzburg in Germany, reported on the principles, research status, and perspectives for these vaccines at the 25th Travel and Health Forum of the Center for Travel Medicine in Berlin.

To understand the future, the immunologist first examined the past. “The induction of cellular and humoral immune responses by externally injected mRNA was discovered in the 1990s,” she said.
 

Instability Challenge

Significant hurdles in mRNA vaccinations included the instability of mRNA and the immune system’s ability to identify foreign mRNA as a threat and destroy mRNA fragments. “The breakthrough toward vaccination came through Dr. Katalin Karikó, who, along with Dr. Drew Weissman, both of the University of Pennsylvania School of Medicine, discovered in 2005 that modifications of mRNA (replacing the nucleoside uridine with pseudouridine) enable better stability of mRNA, reduced immunogenicity, and higher translational capacity at the ribosomes,” said Dr. Prelog.

With this discovery, the two researchers paved the way for the development of mRNA vaccines against COVID-19 and other diseases. They were awarded the Nobel Prize in medicine for their discovery last year.
 

Improved Scalability

“Since 2009, mRNA vaccines have been studied as a treatment option for cancer,” said Dr. Prelog. “Since 2012, they have been studied for the influenza virus and respiratory syncytial virus [RSV].” Consequently, several mRNA vaccines are currently in development or in approval studies. “The mRNA technology offers the advantage of quickly and flexibly responding to new variants of pathogens and the ability to scale up production when there is high demand for a particular vaccine.”

Different forms and designations of mRNA vaccines are used, depending on the application and desired effect, said Dr. Prelog.

In nucleoside-modified mRNA vaccines, modifications in the mRNA sequence enable the mRNA to remain in the body longer and to induce protein synthesis more effectively.

Lipid nanoparticle (LNP)–encapsulated mRNA vaccines protect the coding mRNA sequences against degradation by the body’s enzymes and facilitate the uptake of mRNA into cells, where it then triggers the production of the desired protein. In addition, LNPs are involved in cell stimulation and support the self-adjuvant effect of mRNA vaccines, thus eliminating the need for adjuvants.

Self-amplifying mRNA vaccines include a special mRNA that replicates itself in the cell and contains a sequence for RNA replicase, in addition to the coding sequence for the protein. This composition enables increased production of the target protein without the need for a high amount of external mRNA administration. Such vaccines could trigger a longer and stronger immune response because the immune system has more time to interact with the protein.
 

Cancer Immunotherapy

Dr. Prelog also discussed personalized vaccines for cancer immunotherapy. Personalized mRNA vaccines are tailored to the patient’s genetic characteristics and antigens. They could be used in cancer immunotherapy to activate the immune system selectively against tumor cells.

Multivalent mRNA vaccines contain mRNA that codes for multiple antigens rather than just one protein to generate an immune response. These vaccines could be particularly useful in fighting pathogens with variable or changing surface structures or in eliciting protection against multiple pathogens simultaneously.

The technology of mRNA-encoded antibodies involves introducing mRNA into the cell, which creates light and heavy chains of antibodies. This step leads to the formation of antibodies targeted against toxins (eg, diphtheria and tetanus), animal venoms, infectious agents, or tumor cells.
 

Genetic Engineering

Dr. Prelog also reviewed genetic engineering techniques. In regenerative therapy or protein replacement therapy, skin fibroblasts or other cells are transfected with mRNA to enable conversion into induced pluripotent stem cells. This approach avoids the risk for DNA integration into the genome and associated mutation risks.

Another approach is making post-transcriptional modifications through RNA interference. For example, RNA structures can be used to inhibit the translation of disease-causing proteins. This technique is currently being tested against HIV and tumors such as melanoma.

In addition, mRNA technologies can be combined with CRISPR/Cas9 technology (“gene scissors”) to influence the creation of gene products even more precisely. The advantage of this technique is that mRNA is only transiently expressed, thus preventing unwanted side effects. Furthermore, mRNA is translated directly in the cytoplasm, leading to a faster initiation of gene editing.

Of the numerous ongoing clinical mRNA vaccine studies, around 70% focus on infections, about 12% on cancer, and the rest on autoimmune diseases and neurodegenerative disorders, said Dr. Prelog.
 

Research in Infections

Research in the fields of infectious diseases and oncology is the most advanced: mRNA vaccines against influenza and RSV are already in advanced clinical trials, Dr. Prelog told this news organization.

“Conventional influenza vaccines contain immunogenic surface molecules against hemagglutinin and neuraminidase in various combinations of influenza strains A and B and are produced in egg or cell cultures,” she said. “This is a time-consuming manufacturing process that takes months and, particularly with the egg-based process, bears the risk of changing the vaccine strain.”

“Additionally, influenza viruses undergo antigenic shift and drift through recombination, thus requiring annual adjustments to the vaccines. Thus, these influenza vaccines often lose accuracy in targeting circulating seasonal influenza strains.”

Several mRNA vaccines being tested contain not only coding sequences against hemagglutinin and neuraminidase but also for structural proteins of influenza viruses. “These are more conserved and mutate less easily, meaning they could serve as the basis for universal pandemic influenza vaccines,” said Dr. Prelog.

An advantage of mRNA vaccines, she added, is the strong cellular immune response that they elicit. This response is intended to provide additional protection alongside specific antibodies. An mRNA vaccine with coding sequences for the pre-fusion protein of RSV is in phase 3 trials for approval for vaccination in patients aged 60 years and older. It shows high effectiveness even in older patients and those with comorbidities.
 

Elaborate Purification Process

Bacterial origin plasmid DNA is used to produce mRNA vaccines. The mRNA vaccines for COVID-19 raised concerns that production-related DNA residues could pose a safety risk and cause autoimmune diseases.

These vaccines “typically undergo a very elaborate purification process,” said Dr. Prelog. “This involves enzymatic digestion with DNase to fragment and deplete plasmid DNA, followed by purification using chromatography columns, so that no safety-relevant DNA fragments should remain afterward.”

Thus, the Paul-Ehrlich-Institut also pointed out the very small, fragmented plasmid DNA residues of bacterial origin in mRNA COVID-19 vaccines pose no risk, unlike residual DNA from animal cell culture might pose in other vaccines.
 

Prevention and Therapy

In addition to the numerous advantages of mRNA vaccines (such as rapid adaptability to new or mutated pathogens, scalability, rapid production capability, self-adjuvant effect, strong induction of cellular immune responses, and safety), there are also challenges in RNA technology as a preventive and therapeutic measure, according to Dr. Prelog.

“Stability and storability, as well as the costs of new vaccine developments, play a role, as do the long-term effects regarding the persistence of antibody and cellular responses,” she said. The COVID-19 mRNA vaccines, for example, showed a well-maintained cellular immune response despite a tendency toward a rapid decline in humoral immune response.

“The experience with COVID-19 mRNA vaccines and the new vaccine developments based on mRNA technology give hope for an efficient and safe preventive and therapeutic use, particularly in the fields of infectious diseases and oncology,” Dr. Prelog concluded.

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Cisplatin is a preferred treatment for a wide range of cancers, including breast, head and neck, lung, ovary, and more. However, its side effects — particularly nephrotoxicity — can be severe. Kidney injury on cisplatin is associated with higher mortality and can jeopardize a patient’s eligibility for other therapies.

Now, in a large study using data from six US cancer centers, researchers have developed a risk algorithm to predict acute kidney injury (AKI) after cisplatin administration.

A risk prediction calculator based on the algorithm is available online for patients and providers to determine an individual patient›s risk for kidney injury from cisplatin using readily available clinical data.

Other risk scores and risk prediction models have been developed to help clinicians assess in advance whether a patient might develop AKI after receiving cisplatin, so that more careful monitoring, dose adjustments, or an alternative treatment, if available, might be considered.

However, previous models were limited by factors such as small sample sizes, lack of external validation, older data, and liberal definitions of AKI, said Shruti Gupta, MD, MPH, director of onco-nephrology at Brigham and Women’s Hospital (BWH) and Dana-Farber Cancer Institute, and David E. Leaf, MD, MMSc, director of clinical and translational research in AKI, Division of Renal Medicine, BWH, Boston.

Dr. Gupta and Dr. Leaf believe their risk score for predicting severe AKI after intravenous (IV) cisplatin, published online in The BMJ, is “more accurate and generalizable than prior models for several reasons,” they told this news organization in a joint email.

“First, we externally validated our findings across cancer centers other than the one where it was developed,” they said. “Second, we focused on moderate to severe kidney injury, the most clinically relevant form of kidney damage, whereas prior models examined more mild forms of kidney injury. Third, we collected data on nearly 25,000 patients receiving their first dose of IV cisplatin, which is larger than all previous studies combined.”
 

‘Herculean Effort’

“We conceived of this study back in 2018, contacted collaborators at each participating cancer center, and had numerous meetings to try to gather granular data on patients treated with their first dose of intravenous (IV) cisplatin,” Dr. Gupta and Dr. Leaf explained. They also incorporated patient feedback from focus groups and surveys.

“This was truly a Herculean effort that involved physicians, programmers, research coordinators, and patients,” they said.

The multicenter study included 24,717 patients — 11,766 in the derivation cohort and 12,951 in the validation cohort. Overall, the median age was about 60 years, about 58% were men, and about 78% were White.

The primary outcome was cisplatin-induced AKI (CP-AKI), defined as a twofold or greater increase in serum creatinine or kidney replacement therapy within 14 days of a first dose of IV cisplatin.

The researchers found that the incidence of CP-AKI was 5.2% in the derivation cohort and 3.3% in the validation cohort. Their simple risk score consisting of nine covariates — age, hypertension, type 2 diabetes, hemoglobin level, white blood cell count, platelet count, serum albumin level, serum magnesium level, and cisplatin dose — predicted a higher risk for CP-AKI in both cohorts.

Notably, adding serum creatinine to the model did not change the area under the curve, and therefore, serum creatinine, though also an independent risk factor for CP-AKI, was not included in the score.

Patients in the highest risk category had 24-fold higher odds of CP-AKI in the derivation cohort and close to 18-fold higher odds in the validation cohort than those in the lowest risk category.

The primary model had a C statistic of 0.75 (95% CI, 0.73-0.76) and showed better discrimination for CP-AKI than previously published models, for which the C statistics ranged from 0.60 to 0.68. The first author of a paper on an earlier model, Shveta Motwani, MD, MMSc, of BWH and Dana-Farber Cancer Institute in Boston, is also a coauthor of the new study.

Greater severity of CP-AKI was associated with shorter 90-day survival (adjusted hazard ratio, 4.63; 95% CI, 3.56-6.02) for stage III CP-AKI vs no CP-AKI.
 

‘Definitive Work’

Joel M. Topf, MD, a nephrologist with expertise in chronic kidney disease in Detroit, who wasn’t involved in the development of the risk score, called the study “a definitive work on an important concept in oncology and nephrology.”

“While this is not the first attempt to devise a risk score, it is by far the biggest,” he told this news organization. Furthermore, the authors “used a diverse population, recruiting patients with a variety of cancers (previous attempts had often used a homogenous diagnosis, putting into question how generalizable the results were) from six different cancer centers.”

In addition, he said, “The authors did not restrict patients with chronic kidney disease or other significant comorbidities and used the geographic diversity to produce a cohort that has an age, gender, racial, and ethnic distribution, which is more representative of the US than previous, single-center attempts to risk score patients.”

An earlier model used the Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI of an increase in serum creatinine of 0.3 mg/dL, he noted. “While a sensitive definition of AKI, it captures mild, hemodynamic increases in creatinine of questionable significance,” he said.

By contrast, the new score uses KDIGO stage II and above to define AKI. “This is a better choice, as we do not want to dissuade patients and doctors from choosing chemotherapy due to a fear of insignificant kidney damage,” he said.

All that said, Dr. Topf noted that neither the current score nor the earlier model included serum creatinine. “This is curious to me and may represent the small number of patients with representative elevated creatinine in the derivation cohort (only 1.3% with an estimated glomerular filtration rate [eGFR] < 45).”

“Since the cohort is made up of people who received cis-platinum, the low prevalence of eGFRs < 45 may be due to physicians steering away from cis-platinum in this group,” he suggested. “It would be unfortunate if this risk score gave an unintentional ‘green light’ to these patients, exposing them to predictable harm.”
 

‘Certainly Useful’

Anushree Shirali, MD, an associate professor in the Section of Nephrology and consulting physician, Yale Onco-Nephrology, Yale School of Medicine, in New Haven, Connecticut, said that having a prediction score for which patients are more likely to develop AKI after a single dose of cisplatin would be helpful for oncologists, as well as nephrologists.

As a nephrologist, Dr. Shirali mostly sees patients who already have AKI, she told this news organization. But there are circumstances in which the tool could still be helpful.

“Let’s say someone has abnormal kidney function at baseline — ie, creatinine is higher than the normal range — and they were on dialysis 5 years ago for something else, and now, they have cancer and may be given cisplatin. They worry about their chances of getting AKI and needing dialysis again,” she said. “That’s just one scenario in which I might be asked to answer that question and the tool would certainly be useful.”

Other scenarios could include someone who has just one kidney because they donated a kidney for transplant years ago, and now, they have a malignancy and wonder what their actual risk is of getting kidney issues on cisplatin.

Oncologists could use the tool to determine whether a patient should be treated with cisplatin, or if they’re at high risk, whether an alternative that’s not nephrotoxic might be used. By contrast, “if somebody’s low risk and an oncologist thinks cisplatin is the best agent they have, then they might want to go ahead and use it,” Dr. Shirali said.

Future research could take into consideration that CP-AKI is dose dependent, she suggested, because a prediction score that included the number of cisplatin doses could be even more helpful to determine risk. And, even though the derivation and validation cohorts for the new tool are representative of the US population, additional research should also include more racial/ethnic diversity, she said.

Dr. Gupta and Dr. Leaf hope their tool “will be utilized immediately by patients and providers to help predict an individual’s risk of cisplatin-associated kidney damage. It is easy to use, available for free online, and incorporates readily available clinical variables.”

If a patient is at high risk, the clinical team can consider preventive measures such as administering more IV fluids before receiving cisplatin or monitoring kidney function more closely afterward, they suggested.

Dr. Gupta reported research support from the National Institutes of Health (NIH) and the National Institute of Diabetes and Digestive and Kidney Diseases. She also reported research funding from BTG International, GE HealthCare, and AstraZeneca outside the submitted work. She is a member of GlaxoSmithKline’s Global Anemia Council, a consultant for Secretome and Proletariat Therapeutics, and founder and president emeritus of the American Society of Onconephrology (unpaid). Dr. Leaf is supported by NIH grants, reported research support from BioPorto, BTG International, and Metro International Biotech, and has served as a consultant. Dr. Topf reported an ownership stake in a few DaVita-run dialysis clinics. He also runs a vascular access center and has participated in advisory boards with Cara Therapeutics, Vifor, Astra Zeneca, Bayer, Renibus Therapeutics, Travere Therapeutics, and GlaxoSmithKline. He is president of NephJC, a nonprofit educational organization with no industry support. Dr. Shirali declared no competing interests.

A version of this article appeared on Medscape.com.

Cisplatin is a preferred treatment for a wide range of cancers, including breast, head and neck, lung, ovary, and more. However, its side effects — particularly nephrotoxicity — can be severe. Kidney injury on cisplatin is associated with higher mortality and can jeopardize a patient’s eligibility for other therapies.

Now, in a large study using data from six US cancer centers, researchers have developed a risk algorithm to predict acute kidney injury (AKI) after cisplatin administration.

A risk prediction calculator based on the algorithm is available online for patients and providers to determine an individual patient›s risk for kidney injury from cisplatin using readily available clinical data.

Other risk scores and risk prediction models have been developed to help clinicians assess in advance whether a patient might develop AKI after receiving cisplatin, so that more careful monitoring, dose adjustments, or an alternative treatment, if available, might be considered.

However, previous models were limited by factors such as small sample sizes, lack of external validation, older data, and liberal definitions of AKI, said Shruti Gupta, MD, MPH, director of onco-nephrology at Brigham and Women’s Hospital (BWH) and Dana-Farber Cancer Institute, and David E. Leaf, MD, MMSc, director of clinical and translational research in AKI, Division of Renal Medicine, BWH, Boston.

Dr. Gupta and Dr. Leaf believe their risk score for predicting severe AKI after intravenous (IV) cisplatin, published online in The BMJ, is “more accurate and generalizable than prior models for several reasons,” they told this news organization in a joint email.

“First, we externally validated our findings across cancer centers other than the one where it was developed,” they said. “Second, we focused on moderate to severe kidney injury, the most clinically relevant form of kidney damage, whereas prior models examined more mild forms of kidney injury. Third, we collected data on nearly 25,000 patients receiving their first dose of IV cisplatin, which is larger than all previous studies combined.”
 

‘Herculean Effort’

“We conceived of this study back in 2018, contacted collaborators at each participating cancer center, and had numerous meetings to try to gather granular data on patients treated with their first dose of intravenous (IV) cisplatin,” Dr. Gupta and Dr. Leaf explained. They also incorporated patient feedback from focus groups and surveys.

“This was truly a Herculean effort that involved physicians, programmers, research coordinators, and patients,” they said.

The multicenter study included 24,717 patients — 11,766 in the derivation cohort and 12,951 in the validation cohort. Overall, the median age was about 60 years, about 58% were men, and about 78% were White.

The primary outcome was cisplatin-induced AKI (CP-AKI), defined as a twofold or greater increase in serum creatinine or kidney replacement therapy within 14 days of a first dose of IV cisplatin.

The researchers found that the incidence of CP-AKI was 5.2% in the derivation cohort and 3.3% in the validation cohort. Their simple risk score consisting of nine covariates — age, hypertension, type 2 diabetes, hemoglobin level, white blood cell count, platelet count, serum albumin level, serum magnesium level, and cisplatin dose — predicted a higher risk for CP-AKI in both cohorts.

Notably, adding serum creatinine to the model did not change the area under the curve, and therefore, serum creatinine, though also an independent risk factor for CP-AKI, was not included in the score.

Patients in the highest risk category had 24-fold higher odds of CP-AKI in the derivation cohort and close to 18-fold higher odds in the validation cohort than those in the lowest risk category.

The primary model had a C statistic of 0.75 (95% CI, 0.73-0.76) and showed better discrimination for CP-AKI than previously published models, for which the C statistics ranged from 0.60 to 0.68. The first author of a paper on an earlier model, Shveta Motwani, MD, MMSc, of BWH and Dana-Farber Cancer Institute in Boston, is also a coauthor of the new study.

Greater severity of CP-AKI was associated with shorter 90-day survival (adjusted hazard ratio, 4.63; 95% CI, 3.56-6.02) for stage III CP-AKI vs no CP-AKI.
 

‘Definitive Work’

Joel M. Topf, MD, a nephrologist with expertise in chronic kidney disease in Detroit, who wasn’t involved in the development of the risk score, called the study “a definitive work on an important concept in oncology and nephrology.”

“While this is not the first attempt to devise a risk score, it is by far the biggest,” he told this news organization. Furthermore, the authors “used a diverse population, recruiting patients with a variety of cancers (previous attempts had often used a homogenous diagnosis, putting into question how generalizable the results were) from six different cancer centers.”

In addition, he said, “The authors did not restrict patients with chronic kidney disease or other significant comorbidities and used the geographic diversity to produce a cohort that has an age, gender, racial, and ethnic distribution, which is more representative of the US than previous, single-center attempts to risk score patients.”

An earlier model used the Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI of an increase in serum creatinine of 0.3 mg/dL, he noted. “While a sensitive definition of AKI, it captures mild, hemodynamic increases in creatinine of questionable significance,” he said.

By contrast, the new score uses KDIGO stage II and above to define AKI. “This is a better choice, as we do not want to dissuade patients and doctors from choosing chemotherapy due to a fear of insignificant kidney damage,” he said.

All that said, Dr. Topf noted that neither the current score nor the earlier model included serum creatinine. “This is curious to me and may represent the small number of patients with representative elevated creatinine in the derivation cohort (only 1.3% with an estimated glomerular filtration rate [eGFR] < 45).”

“Since the cohort is made up of people who received cis-platinum, the low prevalence of eGFRs < 45 may be due to physicians steering away from cis-platinum in this group,” he suggested. “It would be unfortunate if this risk score gave an unintentional ‘green light’ to these patients, exposing them to predictable harm.”
 

‘Certainly Useful’

Anushree Shirali, MD, an associate professor in the Section of Nephrology and consulting physician, Yale Onco-Nephrology, Yale School of Medicine, in New Haven, Connecticut, said that having a prediction score for which patients are more likely to develop AKI after a single dose of cisplatin would be helpful for oncologists, as well as nephrologists.

As a nephrologist, Dr. Shirali mostly sees patients who already have AKI, she told this news organization. But there are circumstances in which the tool could still be helpful.

“Let’s say someone has abnormal kidney function at baseline — ie, creatinine is higher than the normal range — and they were on dialysis 5 years ago for something else, and now, they have cancer and may be given cisplatin. They worry about their chances of getting AKI and needing dialysis again,” she said. “That’s just one scenario in which I might be asked to answer that question and the tool would certainly be useful.”

Other scenarios could include someone who has just one kidney because they donated a kidney for transplant years ago, and now, they have a malignancy and wonder what their actual risk is of getting kidney issues on cisplatin.

Oncologists could use the tool to determine whether a patient should be treated with cisplatin, or if they’re at high risk, whether an alternative that’s not nephrotoxic might be used. By contrast, “if somebody’s low risk and an oncologist thinks cisplatin is the best agent they have, then they might want to go ahead and use it,” Dr. Shirali said.

Future research could take into consideration that CP-AKI is dose dependent, she suggested, because a prediction score that included the number of cisplatin doses could be even more helpful to determine risk. And, even though the derivation and validation cohorts for the new tool are representative of the US population, additional research should also include more racial/ethnic diversity, she said.

Dr. Gupta and Dr. Leaf hope their tool “will be utilized immediately by patients and providers to help predict an individual’s risk of cisplatin-associated kidney damage. It is easy to use, available for free online, and incorporates readily available clinical variables.”

If a patient is at high risk, the clinical team can consider preventive measures such as administering more IV fluids before receiving cisplatin or monitoring kidney function more closely afterward, they suggested.

Dr. Gupta reported research support from the National Institutes of Health (NIH) and the National Institute of Diabetes and Digestive and Kidney Diseases. She also reported research funding from BTG International, GE HealthCare, and AstraZeneca outside the submitted work. She is a member of GlaxoSmithKline’s Global Anemia Council, a consultant for Secretome and Proletariat Therapeutics, and founder and president emeritus of the American Society of Onconephrology (unpaid). Dr. Leaf is supported by NIH grants, reported research support from BioPorto, BTG International, and Metro International Biotech, and has served as a consultant. Dr. Topf reported an ownership stake in a few DaVita-run dialysis clinics. He also runs a vascular access center and has participated in advisory boards with Cara Therapeutics, Vifor, Astra Zeneca, Bayer, Renibus Therapeutics, Travere Therapeutics, and GlaxoSmithKline. He is president of NephJC, a nonprofit educational organization with no industry support. Dr. Shirali declared no competing interests.

A version of this article appeared on Medscape.com.

Cisplatin is a preferred treatment for a wide range of cancers, including breast, head and neck, lung, ovary, and more. However, its side effects — particularly nephrotoxicity — can be severe. Kidney injury on cisplatin is associated with higher mortality and can jeopardize a patient’s eligibility for other therapies.

Now, in a large study using data from six US cancer centers, researchers have developed a risk algorithm to predict acute kidney injury (AKI) after cisplatin administration.

A risk prediction calculator based on the algorithm is available online for patients and providers to determine an individual patient›s risk for kidney injury from cisplatin using readily available clinical data.

Other risk scores and risk prediction models have been developed to help clinicians assess in advance whether a patient might develop AKI after receiving cisplatin, so that more careful monitoring, dose adjustments, or an alternative treatment, if available, might be considered.

However, previous models were limited by factors such as small sample sizes, lack of external validation, older data, and liberal definitions of AKI, said Shruti Gupta, MD, MPH, director of onco-nephrology at Brigham and Women’s Hospital (BWH) and Dana-Farber Cancer Institute, and David E. Leaf, MD, MMSc, director of clinical and translational research in AKI, Division of Renal Medicine, BWH, Boston.

Dr. Gupta and Dr. Leaf believe their risk score for predicting severe AKI after intravenous (IV) cisplatin, published online in The BMJ, is “more accurate and generalizable than prior models for several reasons,” they told this news organization in a joint email.

“First, we externally validated our findings across cancer centers other than the one where it was developed,” they said. “Second, we focused on moderate to severe kidney injury, the most clinically relevant form of kidney damage, whereas prior models examined more mild forms of kidney injury. Third, we collected data on nearly 25,000 patients receiving their first dose of IV cisplatin, which is larger than all previous studies combined.”
 

‘Herculean Effort’

“We conceived of this study back in 2018, contacted collaborators at each participating cancer center, and had numerous meetings to try to gather granular data on patients treated with their first dose of intravenous (IV) cisplatin,” Dr. Gupta and Dr. Leaf explained. They also incorporated patient feedback from focus groups and surveys.

“This was truly a Herculean effort that involved physicians, programmers, research coordinators, and patients,” they said.

The multicenter study included 24,717 patients — 11,766 in the derivation cohort and 12,951 in the validation cohort. Overall, the median age was about 60 years, about 58% were men, and about 78% were White.

The primary outcome was cisplatin-induced AKI (CP-AKI), defined as a twofold or greater increase in serum creatinine or kidney replacement therapy within 14 days of a first dose of IV cisplatin.

The researchers found that the incidence of CP-AKI was 5.2% in the derivation cohort and 3.3% in the validation cohort. Their simple risk score consisting of nine covariates — age, hypertension, type 2 diabetes, hemoglobin level, white blood cell count, platelet count, serum albumin level, serum magnesium level, and cisplatin dose — predicted a higher risk for CP-AKI in both cohorts.

Notably, adding serum creatinine to the model did not change the area under the curve, and therefore, serum creatinine, though also an independent risk factor for CP-AKI, was not included in the score.

Patients in the highest risk category had 24-fold higher odds of CP-AKI in the derivation cohort and close to 18-fold higher odds in the validation cohort than those in the lowest risk category.

The primary model had a C statistic of 0.75 (95% CI, 0.73-0.76) and showed better discrimination for CP-AKI than previously published models, for which the C statistics ranged from 0.60 to 0.68. The first author of a paper on an earlier model, Shveta Motwani, MD, MMSc, of BWH and Dana-Farber Cancer Institute in Boston, is also a coauthor of the new study.

Greater severity of CP-AKI was associated with shorter 90-day survival (adjusted hazard ratio, 4.63; 95% CI, 3.56-6.02) for stage III CP-AKI vs no CP-AKI.
 

‘Definitive Work’

Joel M. Topf, MD, a nephrologist with expertise in chronic kidney disease in Detroit, who wasn’t involved in the development of the risk score, called the study “a definitive work on an important concept in oncology and nephrology.”

“While this is not the first attempt to devise a risk score, it is by far the biggest,” he told this news organization. Furthermore, the authors “used a diverse population, recruiting patients with a variety of cancers (previous attempts had often used a homogenous diagnosis, putting into question how generalizable the results were) from six different cancer centers.”

In addition, he said, “The authors did not restrict patients with chronic kidney disease or other significant comorbidities and used the geographic diversity to produce a cohort that has an age, gender, racial, and ethnic distribution, which is more representative of the US than previous, single-center attempts to risk score patients.”

An earlier model used the Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI of an increase in serum creatinine of 0.3 mg/dL, he noted. “While a sensitive definition of AKI, it captures mild, hemodynamic increases in creatinine of questionable significance,” he said.

By contrast, the new score uses KDIGO stage II and above to define AKI. “This is a better choice, as we do not want to dissuade patients and doctors from choosing chemotherapy due to a fear of insignificant kidney damage,” he said.

All that said, Dr. Topf noted that neither the current score nor the earlier model included serum creatinine. “This is curious to me and may represent the small number of patients with representative elevated creatinine in the derivation cohort (only 1.3% with an estimated glomerular filtration rate [eGFR] < 45).”

“Since the cohort is made up of people who received cis-platinum, the low prevalence of eGFRs < 45 may be due to physicians steering away from cis-platinum in this group,” he suggested. “It would be unfortunate if this risk score gave an unintentional ‘green light’ to these patients, exposing them to predictable harm.”
 

‘Certainly Useful’

Anushree Shirali, MD, an associate professor in the Section of Nephrology and consulting physician, Yale Onco-Nephrology, Yale School of Medicine, in New Haven, Connecticut, said that having a prediction score for which patients are more likely to develop AKI after a single dose of cisplatin would be helpful for oncologists, as well as nephrologists.

As a nephrologist, Dr. Shirali mostly sees patients who already have AKI, she told this news organization. But there are circumstances in which the tool could still be helpful.

“Let’s say someone has abnormal kidney function at baseline — ie, creatinine is higher than the normal range — and they were on dialysis 5 years ago for something else, and now, they have cancer and may be given cisplatin. They worry about their chances of getting AKI and needing dialysis again,” she said. “That’s just one scenario in which I might be asked to answer that question and the tool would certainly be useful.”

Other scenarios could include someone who has just one kidney because they donated a kidney for transplant years ago, and now, they have a malignancy and wonder what their actual risk is of getting kidney issues on cisplatin.

Oncologists could use the tool to determine whether a patient should be treated with cisplatin, or if they’re at high risk, whether an alternative that’s not nephrotoxic might be used. By contrast, “if somebody’s low risk and an oncologist thinks cisplatin is the best agent they have, then they might want to go ahead and use it,” Dr. Shirali said.

Future research could take into consideration that CP-AKI is dose dependent, she suggested, because a prediction score that included the number of cisplatin doses could be even more helpful to determine risk. And, even though the derivation and validation cohorts for the new tool are representative of the US population, additional research should also include more racial/ethnic diversity, she said.

Dr. Gupta and Dr. Leaf hope their tool “will be utilized immediately by patients and providers to help predict an individual’s risk of cisplatin-associated kidney damage. It is easy to use, available for free online, and incorporates readily available clinical variables.”

If a patient is at high risk, the clinical team can consider preventive measures such as administering more IV fluids before receiving cisplatin or monitoring kidney function more closely afterward, they suggested.

Dr. Gupta reported research support from the National Institutes of Health (NIH) and the National Institute of Diabetes and Digestive and Kidney Diseases. She also reported research funding from BTG International, GE HealthCare, and AstraZeneca outside the submitted work. She is a member of GlaxoSmithKline’s Global Anemia Council, a consultant for Secretome and Proletariat Therapeutics, and founder and president emeritus of the American Society of Onconephrology (unpaid). Dr. Leaf is supported by NIH grants, reported research support from BioPorto, BTG International, and Metro International Biotech, and has served as a consultant. Dr. Topf reported an ownership stake in a few DaVita-run dialysis clinics. He also runs a vascular access center and has participated in advisory boards with Cara Therapeutics, Vifor, Astra Zeneca, Bayer, Renibus Therapeutics, Travere Therapeutics, and GlaxoSmithKline. He is president of NephJC, a nonprofit educational organization with no industry support. Dr. Shirali declared no competing interests.

A version of this article appeared on Medscape.com.

The expression of the protein Nectin-4 can predict how patients with metastatic urothelial cancer (m)UC will respond to the anti-Nectin-4 antibody-drug conjugate (ADC) enfortumab vedotin (EV), a new study finds.

Identifying biomarkers to predict how patients will respond to targeted therapies is crucial to improve treatments for patients with cancer, authors Niklas Klümper, MD, with the Department of Urology and Pediatric Urology at University Hospital Bonn, in Germany, and colleagues, wrote in the Journal of Clinical Oncology (doi: 10.1200/JCO.23.01983).

The researchers used a Nectin-4-specific fluorescence in situ hybridization (FISH) assay in an (m)UC cohort of 108 patients to test Nectin-4’s ability to predict responses, analyzing slides with a fluorescence microscope. The copy number variations (CNVs) were correlated with membranous Nectin-4 protein expression, responses to EV treatment, and outcomes.

They also evaluated the prognostic value of Nectin-4 CNVs with biopsies of 103 (m)UC patients not treated with EV. Additionally, they searched The Cancer Genome Atlas (TCGA) data sets (10,712 patients across 32 cancer types) for Nectin-4 CNVs.
 

Why Was This Study Done?

Urothelial carcinoma accounts for 90% of bladder cancer cases globally. Though EV was approved to treat (m)UC in 2019, lasting benefit has been achieved only in a small subset of patients.

EV is given to all without selecting patients based on biomarkers that may predict how well they will respond to EV. In this study, researchers investigated whether response to EV was better when people had amplification — defined as increased numbers of copies — of Nectin-4.
 

How Common Is It for Patients With (m)UC to Have Nectin-4 Amplifications?

Nectin-4 amplifications happen frequently in (m)UC; they occurred in about 26% of the (m)UC patients the researchers studied, according to the new paper.

The amplifications are frequent in other cancer types as well, and this study suggests that this biomarker is a promising candidate for developing Nectin-4–targeted antibody-drug conjugates for other cancers.

“Nectin-4 amplifications can be found in 5%-10% of breast cancer and non–small cell lung cancer, both tumor types with a high impact on all-cancer mortality, which are currently being evaluated for EV response,” the authors wrote.

Currently, (m)UC is the only cancer for which EV is approved as standard-of-care, the researchers explain, in their paper.
 

What Were the Differences Between the EV and Non-EV Groups?

Almost all (27 of the 28) patients in the cohort (96%) who had Nectin-4 amplifications had objective responses to EV compared with 24 of 74 (32%) in the group without amplifications (P less than .001). Among the 96% with a response, 82% had partial response and 14% had a complete response.

The amplifications for those treated with EV were linked with longer progression-free survival (90% 12-month PFS vs 41% for those with nonamplified tumors) and longer overall survival (OS).

For those patients treated with EV who had the amplifications, OS was not reached. This was because the researchers could not calculate the OS at 12 months for this group due to more than half of the patients still being alive at that time. That finding contrasts with a median OS of 8.8 months in those patients treated with EV who did not have the amplifications.

EV-treated patients who had Nectin-4 amplifications had a 92% lower risk of death compared with EV-treated patients without the amplifications, according to an analysis that adjusted for factors including age and sex.

“Importantly, in the non–EV-treated patients with (m)UC, Nectin-4 amplifications have no impact on OS [overall survival], suggesting that Nectin-4 amplifications are neither indicating aggressive nor favorable tumor biology, strengthening its potential value as a pure predictive biomarker,” the researchers wrote.
 

What Are the Implications of These Findings?

“[O]ur study suggests that Nectin-4 amplification is a simple, valuable, and easy-to-implement predictive biomarker for EV in patients with (m)UC. The frequent occurrence of Nectin-4 amplifications in other cancer types suggests that this biomarker is a promising candidate with broader applicability for clinical development of Nectin-4-targeted ADCs in a tumor-agnostic context.”

Choosing the best therapy sequence for (m)UC is crucial, the authors write. Considering Nectin-4 amplifications could inform EV drug development — even at earlier stages of the disease — by defining which patient subgroup has the highest chance for long-term benefit.

The authors acknowledge that the primary limitation of the study is that it is retrospective, using archived primary and metastatic tumor specimens with varying ranges between the time of tumor sampling and start of EV treatment.

“Therefore, our data are hypothesis-generating and prospective confirmation in larger, biomarker-driven trials is mandatory,” the authors wrote.

They note that EV plus pembrolizumab [Keytruda] (EV/P) was recently approved as the new standard of care in first-line treatment for (m)UC, so the predictive value of Nectin-4 amplification in this new treatment setting warrants further research.

Dr. Klümper reports stock and other ownership interests in Bicycle Therapeutics, Pfizer, Daiichi Sankyo/UCB Japan, and Immatics; and honoraria for Astellas Pharma and MSD Oncology; and consulting or advisory roles with Astellas Pharma, MSD Oncology, and Eisai. He reports travel reimbursements from Ipsen, Photocure, and MSD Oncology. Other author disclosures are available with the full text of the paper.

The expression of the protein Nectin-4 can predict how patients with metastatic urothelial cancer (m)UC will respond to the anti-Nectin-4 antibody-drug conjugate (ADC) enfortumab vedotin (EV), a new study finds.

Identifying biomarkers to predict how patients will respond to targeted therapies is crucial to improve treatments for patients with cancer, authors Niklas Klümper, MD, with the Department of Urology and Pediatric Urology at University Hospital Bonn, in Germany, and colleagues, wrote in the Journal of Clinical Oncology (doi: 10.1200/JCO.23.01983).

The researchers used a Nectin-4-specific fluorescence in situ hybridization (FISH) assay in an (m)UC cohort of 108 patients to test Nectin-4’s ability to predict responses, analyzing slides with a fluorescence microscope. The copy number variations (CNVs) were correlated with membranous Nectin-4 protein expression, responses to EV treatment, and outcomes.

They also evaluated the prognostic value of Nectin-4 CNVs with biopsies of 103 (m)UC patients not treated with EV. Additionally, they searched The Cancer Genome Atlas (TCGA) data sets (10,712 patients across 32 cancer types) for Nectin-4 CNVs.
 

Why Was This Study Done?

Urothelial carcinoma accounts for 90% of bladder cancer cases globally. Though EV was approved to treat (m)UC in 2019, lasting benefit has been achieved only in a small subset of patients.

EV is given to all without selecting patients based on biomarkers that may predict how well they will respond to EV. In this study, researchers investigated whether response to EV was better when people had amplification — defined as increased numbers of copies — of Nectin-4.
 

How Common Is It for Patients With (m)UC to Have Nectin-4 Amplifications?

Nectin-4 amplifications happen frequently in (m)UC; they occurred in about 26% of the (m)UC patients the researchers studied, according to the new paper.

The amplifications are frequent in other cancer types as well, and this study suggests that this biomarker is a promising candidate for developing Nectin-4–targeted antibody-drug conjugates for other cancers.

“Nectin-4 amplifications can be found in 5%-10% of breast cancer and non–small cell lung cancer, both tumor types with a high impact on all-cancer mortality, which are currently being evaluated for EV response,” the authors wrote.

Currently, (m)UC is the only cancer for which EV is approved as standard-of-care, the researchers explain, in their paper.
 

What Were the Differences Between the EV and Non-EV Groups?

Almost all (27 of the 28) patients in the cohort (96%) who had Nectin-4 amplifications had objective responses to EV compared with 24 of 74 (32%) in the group without amplifications (P less than .001). Among the 96% with a response, 82% had partial response and 14% had a complete response.

The amplifications for those treated with EV were linked with longer progression-free survival (90% 12-month PFS vs 41% for those with nonamplified tumors) and longer overall survival (OS).

For those patients treated with EV who had the amplifications, OS was not reached. This was because the researchers could not calculate the OS at 12 months for this group due to more than half of the patients still being alive at that time. That finding contrasts with a median OS of 8.8 months in those patients treated with EV who did not have the amplifications.

EV-treated patients who had Nectin-4 amplifications had a 92% lower risk of death compared with EV-treated patients without the amplifications, according to an analysis that adjusted for factors including age and sex.

“Importantly, in the non–EV-treated patients with (m)UC, Nectin-4 amplifications have no impact on OS [overall survival], suggesting that Nectin-4 amplifications are neither indicating aggressive nor favorable tumor biology, strengthening its potential value as a pure predictive biomarker,” the researchers wrote.
 

What Are the Implications of These Findings?

“[O]ur study suggests that Nectin-4 amplification is a simple, valuable, and easy-to-implement predictive biomarker for EV in patients with (m)UC. The frequent occurrence of Nectin-4 amplifications in other cancer types suggests that this biomarker is a promising candidate with broader applicability for clinical development of Nectin-4-targeted ADCs in a tumor-agnostic context.”

Choosing the best therapy sequence for (m)UC is crucial, the authors write. Considering Nectin-4 amplifications could inform EV drug development — even at earlier stages of the disease — by defining which patient subgroup has the highest chance for long-term benefit.

The authors acknowledge that the primary limitation of the study is that it is retrospective, using archived primary and metastatic tumor specimens with varying ranges between the time of tumor sampling and start of EV treatment.

“Therefore, our data are hypothesis-generating and prospective confirmation in larger, biomarker-driven trials is mandatory,” the authors wrote.

They note that EV plus pembrolizumab [Keytruda] (EV/P) was recently approved as the new standard of care in first-line treatment for (m)UC, so the predictive value of Nectin-4 amplification in this new treatment setting warrants further research.

Dr. Klümper reports stock and other ownership interests in Bicycle Therapeutics, Pfizer, Daiichi Sankyo/UCB Japan, and Immatics; and honoraria for Astellas Pharma and MSD Oncology; and consulting or advisory roles with Astellas Pharma, MSD Oncology, and Eisai. He reports travel reimbursements from Ipsen, Photocure, and MSD Oncology. Other author disclosures are available with the full text of the paper.

The expression of the protein Nectin-4 can predict how patients with metastatic urothelial cancer (m)UC will respond to the anti-Nectin-4 antibody-drug conjugate (ADC) enfortumab vedotin (EV), a new study finds.

Identifying biomarkers to predict how patients will respond to targeted therapies is crucial to improve treatments for patients with cancer, authors Niklas Klümper, MD, with the Department of Urology and Pediatric Urology at University Hospital Bonn, in Germany, and colleagues, wrote in the Journal of Clinical Oncology (doi: 10.1200/JCO.23.01983).

The researchers used a Nectin-4-specific fluorescence in situ hybridization (FISH) assay in an (m)UC cohort of 108 patients to test Nectin-4’s ability to predict responses, analyzing slides with a fluorescence microscope. The copy number variations (CNVs) were correlated with membranous Nectin-4 protein expression, responses to EV treatment, and outcomes.

They also evaluated the prognostic value of Nectin-4 CNVs with biopsies of 103 (m)UC patients not treated with EV. Additionally, they searched The Cancer Genome Atlas (TCGA) data sets (10,712 patients across 32 cancer types) for Nectin-4 CNVs.
 

Why Was This Study Done?

Urothelial carcinoma accounts for 90% of bladder cancer cases globally. Though EV was approved to treat (m)UC in 2019, lasting benefit has been achieved only in a small subset of patients.

EV is given to all without selecting patients based on biomarkers that may predict how well they will respond to EV. In this study, researchers investigated whether response to EV was better when people had amplification — defined as increased numbers of copies — of Nectin-4.
 

How Common Is It for Patients With (m)UC to Have Nectin-4 Amplifications?

Nectin-4 amplifications happen frequently in (m)UC; they occurred in about 26% of the (m)UC patients the researchers studied, according to the new paper.

The amplifications are frequent in other cancer types as well, and this study suggests that this biomarker is a promising candidate for developing Nectin-4–targeted antibody-drug conjugates for other cancers.

“Nectin-4 amplifications can be found in 5%-10% of breast cancer and non–small cell lung cancer, both tumor types with a high impact on all-cancer mortality, which are currently being evaluated for EV response,” the authors wrote.

Currently, (m)UC is the only cancer for which EV is approved as standard-of-care, the researchers explain, in their paper.
 

What Were the Differences Between the EV and Non-EV Groups?

Almost all (27 of the 28) patients in the cohort (96%) who had Nectin-4 amplifications had objective responses to EV compared with 24 of 74 (32%) in the group without amplifications (P less than .001). Among the 96% with a response, 82% had partial response and 14% had a complete response.

The amplifications for those treated with EV were linked with longer progression-free survival (90% 12-month PFS vs 41% for those with nonamplified tumors) and longer overall survival (OS).

For those patients treated with EV who had the amplifications, OS was not reached. This was because the researchers could not calculate the OS at 12 months for this group due to more than half of the patients still being alive at that time. That finding contrasts with a median OS of 8.8 months in those patients treated with EV who did not have the amplifications.

EV-treated patients who had Nectin-4 amplifications had a 92% lower risk of death compared with EV-treated patients without the amplifications, according to an analysis that adjusted for factors including age and sex.

“Importantly, in the non–EV-treated patients with (m)UC, Nectin-4 amplifications have no impact on OS [overall survival], suggesting that Nectin-4 amplifications are neither indicating aggressive nor favorable tumor biology, strengthening its potential value as a pure predictive biomarker,” the researchers wrote.
 

What Are the Implications of These Findings?

“[O]ur study suggests that Nectin-4 amplification is a simple, valuable, and easy-to-implement predictive biomarker for EV in patients with (m)UC. The frequent occurrence of Nectin-4 amplifications in other cancer types suggests that this biomarker is a promising candidate with broader applicability for clinical development of Nectin-4-targeted ADCs in a tumor-agnostic context.”

Choosing the best therapy sequence for (m)UC is crucial, the authors write. Considering Nectin-4 amplifications could inform EV drug development — even at earlier stages of the disease — by defining which patient subgroup has the highest chance for long-term benefit.

The authors acknowledge that the primary limitation of the study is that it is retrospective, using archived primary and metastatic tumor specimens with varying ranges between the time of tumor sampling and start of EV treatment.

“Therefore, our data are hypothesis-generating and prospective confirmation in larger, biomarker-driven trials is mandatory,” the authors wrote.

They note that EV plus pembrolizumab [Keytruda] (EV/P) was recently approved as the new standard of care in first-line treatment for (m)UC, so the predictive value of Nectin-4 amplification in this new treatment setting warrants further research.

Dr. Klümper reports stock and other ownership interests in Bicycle Therapeutics, Pfizer, Daiichi Sankyo/UCB Japan, and Immatics; and honoraria for Astellas Pharma and MSD Oncology; and consulting or advisory roles with Astellas Pharma, MSD Oncology, and Eisai. He reports travel reimbursements from Ipsen, Photocure, and MSD Oncology. Other author disclosures are available with the full text of the paper.

A plastic surgeon broke federal law when he restricted patients from posting negative reviews by requiring them to sign nondisclosure agreements before they received care, a district judge has ruled.

Seattle-based surgeon Javad Sajan, MD, ran afoul of the Consumer Review Fairness Act (CRFA) by requiring more than 10,000 patients to sign the agreements, according to a recent decision by US District Judge Ricardo S. Martinez. The law protects consumers’ rights to post truthful reviews about businesses. 

Judge Martinez wrote that the terms of Dr. Sajan’s nondisclosure agreements “clearly include language prohibiting or restricting patients from posting negative reviews,” in violation of CRFA. Penalties for the offense will be determined at a September trial. 

This news organization contacted Dr. Sajan’s office and his attorney for comment but did not get a response. 

The decision is the latest development in an ongoing legal dispute between Dr. Sajan and the State of Washington over whether the surgeon’s efforts to limit negative online reviews were illegal. 

Beginning in 2017, Dr. Sajan and his practice, Allure Esthetic, introduced agreements that “forced” patients to contact the business directly if they had concerns rather than post a negative review, according to a 2022 lawsuit against Dr. Sajan filed by Washington Attorney General Robert Ferguson. 

“Online reviews are often the first stop when consumers are determining who to trust,” Mr. Ferguson said in a statement. “That’s especially critical when those services deal with a patient’s health and safety. We will take action against those who illegally stop Washingtonians from sharing reviews with the public.”

If patients posted negative reviews, the clinic, in some cases, threatened litigation, according to the complaint. In other cases, patients were allegedly offered money and free services in exchange for taking the reviews down. Patients who accepted cash or services were required to sign a second agreement forbidding them from posting future negative reviews and imposing a $250,000 penalty for failure to comply, according to court documents. 

In court documents, Dr. Sajan’s attorneys argued the agreements did not violate CRFA because patients had the opportunity to modify the language or decline signing them, which hundreds did. The CRFA requires Mr. Ferguson to prove that consumers lacked a meaningful opportunity to negotiate the terms, attorneys for Dr. Sajan argued in court records. 

But Judge Martinez wrote that the patients who declined to sign the agreements or changed the terms represented only a “tiny fraction” of the affected patients.

The agreement language restricts patients from speaking out by forcing dissatisfied patients to work with Allure until a resolution is reached, Judge Martinez noted in his decision. “At the very least, this would delay patients from posting such reviews and force patients to interact in some way with Allure, and it certainly appears to prohibit posting reviews until Allure agrees to some kind of favorable resolution.”
 

Surgeon Posted Fake Positive Reviews to Counteract Bad Reviews, AG Says

Employee accounts in court documents describe a physician fixated on reviews who went to great lengths to ensure positive reviews about his work outweighed the negative. 

Former employees said they were instructed to track down patients who left negative reviews and either “threaten” them to take the posts down or offer them “money” or other things, according to Mr. Ferguson’s lawsuit. If patients could not be identified, the practice would file a defamation lawsuit against the anonymous person who posted the review and use litigation to subpoena the website for the reviewer’s IP address in order to identify them, according to court documents. 

Employees testified they had regular meetings to review current negative reviews and discuss what steps they were taking to get them removed. At team meetings, in-house counsel would regularly present an Excel spreadsheet with updates on progress in getting patients to remove negative reviews, according to court documents. 

In addition to restricting negative reviews, Mr. Ferguson accuses Dr. Sajan of posting fake positive reviews and “buying” thousands of fake followers on social media. 

At Dr. Sajan’s direction, employees created Gmail accounts using stock photos for their profile pictures and used the accounts to post fake reviews of Allure Esthetic and Dr. Sajan, according to the complaint. The practice also used members of an online forum called BlackHatWorld.com to create fake email accounts and to post fake reviews, the attorney general alleges. Many of the fake positive reviews, including the fake Google reviews, still appear on online review sites today, the attorney general contends. 

Dr. Sajan and his practice also allegedly manipulated social media to appear more popular. Mr. Ferguson claims that Dr. Sajan instructed his former web designer to purchase 60,000 followers through a vendor on BlackHatWorld.com. Most of Dr. Sajan’s current Instagram followers are not real, according to Mr. Ferguson. 

The practice also used a social media bot tool to buy thousands of fake likes on Instagram, YouTube, and other social media, according to court documents. 

In addition, Dr. Sajan and his practice are accused of significantly altering “before and after” photos of patients and using fake email accounts to allow the clinic to take skincare rebates intended for patients.

All of these practices violated HIPAA, the state Consumer Protection Act (CPA) and the federal CRFA, according to Mr. Ferguson. 
 

Surgeon Claims Competitor Behind Allegations 

Attorneys for Dr. Sajan argue a competitor is behind the accusations and that other regulatory entities determined the practice did nothing wrong. 

The competitor, a Seattle-based plastic surgeon, filed numerous complaints about Dr. Sajan to the Washington Medical Commission (WMC), according to court documents. The medical commission reviewed the third agreement and closed its investigation, finding that if the allegations were true, “no violation of law occurred,” court records show. 

“Defendants relied upon this closing code from the WMC that the (non-disclosure) forms were lawful,” Dr. Sajan’s attorneys wrote in court documents.

The US Department of Health & Human Services Office for Civil Rights (OCR) also reviewed and audited Dr. Sajan’s use of the agreements, his attorneys noted. In a notice from OCR included in court exhibits, the agency wrote that all matters at issue have now been resolved through the practice’s voluntary compliance actions and that it was closing its investigation. 

Attorneys for Dr. Sajan accuse Mr. Ferguson and state investigators of withholding the full extent of the competitor’s involvement in their investigation and failing to identify the competitor in written discovery or any of its initial disclosures. Dr. Sajan and his team discovered that the competitor was a source of key information through public records requests, according to court documents. 

The remaining claims against Dr. Sajan will be addressed at trial, set for September 9, 2024. 
 

A version of this article appeared on Medscape.com.

A plastic surgeon broke federal law when he restricted patients from posting negative reviews by requiring them to sign nondisclosure agreements before they received care, a district judge has ruled.

Seattle-based surgeon Javad Sajan, MD, ran afoul of the Consumer Review Fairness Act (CRFA) by requiring more than 10,000 patients to sign the agreements, according to a recent decision by US District Judge Ricardo S. Martinez. The law protects consumers’ rights to post truthful reviews about businesses. 

Judge Martinez wrote that the terms of Dr. Sajan’s nondisclosure agreements “clearly include language prohibiting or restricting patients from posting negative reviews,” in violation of CRFA. Penalties for the offense will be determined at a September trial. 

This news organization contacted Dr. Sajan’s office and his attorney for comment but did not get a response. 

The decision is the latest development in an ongoing legal dispute between Dr. Sajan and the State of Washington over whether the surgeon’s efforts to limit negative online reviews were illegal. 

Beginning in 2017, Dr. Sajan and his practice, Allure Esthetic, introduced agreements that “forced” patients to contact the business directly if they had concerns rather than post a negative review, according to a 2022 lawsuit against Dr. Sajan filed by Washington Attorney General Robert Ferguson. 

“Online reviews are often the first stop when consumers are determining who to trust,” Mr. Ferguson said in a statement. “That’s especially critical when those services deal with a patient’s health and safety. We will take action against those who illegally stop Washingtonians from sharing reviews with the public.”

If patients posted negative reviews, the clinic, in some cases, threatened litigation, according to the complaint. In other cases, patients were allegedly offered money and free services in exchange for taking the reviews down. Patients who accepted cash or services were required to sign a second agreement forbidding them from posting future negative reviews and imposing a $250,000 penalty for failure to comply, according to court documents. 

In court documents, Dr. Sajan’s attorneys argued the agreements did not violate CRFA because patients had the opportunity to modify the language or decline signing them, which hundreds did. The CRFA requires Mr. Ferguson to prove that consumers lacked a meaningful opportunity to negotiate the terms, attorneys for Dr. Sajan argued in court records. 

But Judge Martinez wrote that the patients who declined to sign the agreements or changed the terms represented only a “tiny fraction” of the affected patients.

The agreement language restricts patients from speaking out by forcing dissatisfied patients to work with Allure until a resolution is reached, Judge Martinez noted in his decision. “At the very least, this would delay patients from posting such reviews and force patients to interact in some way with Allure, and it certainly appears to prohibit posting reviews until Allure agrees to some kind of favorable resolution.”
 

Surgeon Posted Fake Positive Reviews to Counteract Bad Reviews, AG Says

Employee accounts in court documents describe a physician fixated on reviews who went to great lengths to ensure positive reviews about his work outweighed the negative. 

Former employees said they were instructed to track down patients who left negative reviews and either “threaten” them to take the posts down or offer them “money” or other things, according to Mr. Ferguson’s lawsuit. If patients could not be identified, the practice would file a defamation lawsuit against the anonymous person who posted the review and use litigation to subpoena the website for the reviewer’s IP address in order to identify them, according to court documents. 

Employees testified they had regular meetings to review current negative reviews and discuss what steps they were taking to get them removed. At team meetings, in-house counsel would regularly present an Excel spreadsheet with updates on progress in getting patients to remove negative reviews, according to court documents. 

In addition to restricting negative reviews, Mr. Ferguson accuses Dr. Sajan of posting fake positive reviews and “buying” thousands of fake followers on social media. 

At Dr. Sajan’s direction, employees created Gmail accounts using stock photos for their profile pictures and used the accounts to post fake reviews of Allure Esthetic and Dr. Sajan, according to the complaint. The practice also used members of an online forum called BlackHatWorld.com to create fake email accounts and to post fake reviews, the attorney general alleges. Many of the fake positive reviews, including the fake Google reviews, still appear on online review sites today, the attorney general contends. 

Dr. Sajan and his practice also allegedly manipulated social media to appear more popular. Mr. Ferguson claims that Dr. Sajan instructed his former web designer to purchase 60,000 followers through a vendor on BlackHatWorld.com. Most of Dr. Sajan’s current Instagram followers are not real, according to Mr. Ferguson. 

The practice also used a social media bot tool to buy thousands of fake likes on Instagram, YouTube, and other social media, according to court documents. 

In addition, Dr. Sajan and his practice are accused of significantly altering “before and after” photos of patients and using fake email accounts to allow the clinic to take skincare rebates intended for patients.

All of these practices violated HIPAA, the state Consumer Protection Act (CPA) and the federal CRFA, according to Mr. Ferguson. 
 

Surgeon Claims Competitor Behind Allegations 

Attorneys for Dr. Sajan argue a competitor is behind the accusations and that other regulatory entities determined the practice did nothing wrong. 

The competitor, a Seattle-based plastic surgeon, filed numerous complaints about Dr. Sajan to the Washington Medical Commission (WMC), according to court documents. The medical commission reviewed the third agreement and closed its investigation, finding that if the allegations were true, “no violation of law occurred,” court records show. 

“Defendants relied upon this closing code from the WMC that the (non-disclosure) forms were lawful,” Dr. Sajan’s attorneys wrote in court documents.

The US Department of Health & Human Services Office for Civil Rights (OCR) also reviewed and audited Dr. Sajan’s use of the agreements, his attorneys noted. In a notice from OCR included in court exhibits, the agency wrote that all matters at issue have now been resolved through the practice’s voluntary compliance actions and that it was closing its investigation. 

Attorneys for Dr. Sajan accuse Mr. Ferguson and state investigators of withholding the full extent of the competitor’s involvement in their investigation and failing to identify the competitor in written discovery or any of its initial disclosures. Dr. Sajan and his team discovered that the competitor was a source of key information through public records requests, according to court documents. 

The remaining claims against Dr. Sajan will be addressed at trial, set for September 9, 2024. 
 

A version of this article appeared on Medscape.com.

A plastic surgeon broke federal law when he restricted patients from posting negative reviews by requiring them to sign nondisclosure agreements before they received care, a district judge has ruled.

Seattle-based surgeon Javad Sajan, MD, ran afoul of the Consumer Review Fairness Act (CRFA) by requiring more than 10,000 patients to sign the agreements, according to a recent decision by US District Judge Ricardo S. Martinez. The law protects consumers’ rights to post truthful reviews about businesses. 

Judge Martinez wrote that the terms of Dr. Sajan’s nondisclosure agreements “clearly include language prohibiting or restricting patients from posting negative reviews,” in violation of CRFA. Penalties for the offense will be determined at a September trial. 

This news organization contacted Dr. Sajan’s office and his attorney for comment but did not get a response. 

The decision is the latest development in an ongoing legal dispute between Dr. Sajan and the State of Washington over whether the surgeon’s efforts to limit negative online reviews were illegal. 

Beginning in 2017, Dr. Sajan and his practice, Allure Esthetic, introduced agreements that “forced” patients to contact the business directly if they had concerns rather than post a negative review, according to a 2022 lawsuit against Dr. Sajan filed by Washington Attorney General Robert Ferguson. 

“Online reviews are often the first stop when consumers are determining who to trust,” Mr. Ferguson said in a statement. “That’s especially critical when those services deal with a patient’s health and safety. We will take action against those who illegally stop Washingtonians from sharing reviews with the public.”

If patients posted negative reviews, the clinic, in some cases, threatened litigation, according to the complaint. In other cases, patients were allegedly offered money and free services in exchange for taking the reviews down. Patients who accepted cash or services were required to sign a second agreement forbidding them from posting future negative reviews and imposing a $250,000 penalty for failure to comply, according to court documents. 

In court documents, Dr. Sajan’s attorneys argued the agreements did not violate CRFA because patients had the opportunity to modify the language or decline signing them, which hundreds did. The CRFA requires Mr. Ferguson to prove that consumers lacked a meaningful opportunity to negotiate the terms, attorneys for Dr. Sajan argued in court records. 

But Judge Martinez wrote that the patients who declined to sign the agreements or changed the terms represented only a “tiny fraction” of the affected patients.

The agreement language restricts patients from speaking out by forcing dissatisfied patients to work with Allure until a resolution is reached, Judge Martinez noted in his decision. “At the very least, this would delay patients from posting such reviews and force patients to interact in some way with Allure, and it certainly appears to prohibit posting reviews until Allure agrees to some kind of favorable resolution.”
 

Surgeon Posted Fake Positive Reviews to Counteract Bad Reviews, AG Says

Employee accounts in court documents describe a physician fixated on reviews who went to great lengths to ensure positive reviews about his work outweighed the negative. 

Former employees said they were instructed to track down patients who left negative reviews and either “threaten” them to take the posts down or offer them “money” or other things, according to Mr. Ferguson’s lawsuit. If patients could not be identified, the practice would file a defamation lawsuit against the anonymous person who posted the review and use litigation to subpoena the website for the reviewer’s IP address in order to identify them, according to court documents. 

Employees testified they had regular meetings to review current negative reviews and discuss what steps they were taking to get them removed. At team meetings, in-house counsel would regularly present an Excel spreadsheet with updates on progress in getting patients to remove negative reviews, according to court documents. 

In addition to restricting negative reviews, Mr. Ferguson accuses Dr. Sajan of posting fake positive reviews and “buying” thousands of fake followers on social media. 

At Dr. Sajan’s direction, employees created Gmail accounts using stock photos for their profile pictures and used the accounts to post fake reviews of Allure Esthetic and Dr. Sajan, according to the complaint. The practice also used members of an online forum called BlackHatWorld.com to create fake email accounts and to post fake reviews, the attorney general alleges. Many of the fake positive reviews, including the fake Google reviews, still appear on online review sites today, the attorney general contends. 

Dr. Sajan and his practice also allegedly manipulated social media to appear more popular. Mr. Ferguson claims that Dr. Sajan instructed his former web designer to purchase 60,000 followers through a vendor on BlackHatWorld.com. Most of Dr. Sajan’s current Instagram followers are not real, according to Mr. Ferguson. 

The practice also used a social media bot tool to buy thousands of fake likes on Instagram, YouTube, and other social media, according to court documents. 

In addition, Dr. Sajan and his practice are accused of significantly altering “before and after” photos of patients and using fake email accounts to allow the clinic to take skincare rebates intended for patients.

All of these practices violated HIPAA, the state Consumer Protection Act (CPA) and the federal CRFA, according to Mr. Ferguson. 
 

Surgeon Claims Competitor Behind Allegations 

Attorneys for Dr. Sajan argue a competitor is behind the accusations and that other regulatory entities determined the practice did nothing wrong. 

The competitor, a Seattle-based plastic surgeon, filed numerous complaints about Dr. Sajan to the Washington Medical Commission (WMC), according to court documents. The medical commission reviewed the third agreement and closed its investigation, finding that if the allegations were true, “no violation of law occurred,” court records show. 

“Defendants relied upon this closing code from the WMC that the (non-disclosure) forms were lawful,” Dr. Sajan’s attorneys wrote in court documents.

The US Department of Health & Human Services Office for Civil Rights (OCR) also reviewed and audited Dr. Sajan’s use of the agreements, his attorneys noted. In a notice from OCR included in court exhibits, the agency wrote that all matters at issue have now been resolved through the practice’s voluntary compliance actions and that it was closing its investigation. 

Attorneys for Dr. Sajan accuse Mr. Ferguson and state investigators of withholding the full extent of the competitor’s involvement in their investigation and failing to identify the competitor in written discovery or any of its initial disclosures. Dr. Sajan and his team discovered that the competitor was a source of key information through public records requests, according to court documents. 

The remaining claims against Dr. Sajan will be addressed at trial, set for September 9, 2024. 
 

A version of this article appeared on Medscape.com.

Sherrie Palm, a patient advocate in Mukwonago, Wisconsin, learned in her 30s that she needed to educate herself about her own health. So when she discovered a walnut-sized lump coming out of her vagina in her mid-50s, she was stunned when her primary care provider (PCP) told her it was pelvic organ prolapse (POP), where one or more organs descend into the vaginal cavity.

“I was shocked,” Ms. Palm said. After searching online and discovering how prevalent POP was, her shock turned to anger. “I was blown away that it could be this common and I’d never heard of it,” she said. “I knew within 2 weeks that I had to do something to change the status quo.”

Ms. Palm eventually founded the nonprofit Association for Pelvic Organ Prolapse Support, or APOPS, complete with a forum where women can learn about POP and support one another. She said awareness has improved substantially since her diagnosis in 2007, but “we have a long way to go” because POP and vaginal health in general are so stigmatized.

Her website notes that about half of women with incontinence do not seek help, largely because of stigma. “The status quo is that PCPs do not POP screen,” she said. ObGyns may screen but often “because the patient has asked to be screened, they say it’s not that bad, come back and see me in a year, and do your Kegels,” Ms. Palm said.

Doctors who diagnose POP agree that the issue is often off PCPs’ radar.

“Primary care doctors are really in a time crunch, so this is one of the things that may not get addressed,” Jill Rabin, MD, vice chair of education and development in obstetrics and gynecology at Northwell Health in New York, said. Dr. Rabin is also head of urogynecology at Long Island Jewish Medical Center.

Ann Nwabuebo, PT, DPT, owner and founder of Body Connect Physical Therapy in Bethesda, Maryland, said social media has been shifting the attitude that pelvic health is a taboo subject. “It’s empowering people to seek care if they’re not finding physicians who are helping.”

But social media is also a double-edged sword, said Jenny LaCross, PT, DPT, PhD, a physical therapist at MOVE PT in Monroe, Michigan, and a postdoctoral research fellow with Michigan Medicine’s Pelvic Floor Research Group. “Pelvic health in general is talked about a lot more, but there’s also a lot more misinformation,” she said.

Part of that misinformation is the idea that pelvic prolapse is solely about weakness in the pelvic floor when it can also result from a widening of natural openings within the pelvis, Dr. LaCross said. She pointed to the two definitions of pelvic organ prolapse by the International Urogynecologic Consultation and the International Continence Society, both of which have been updated in recent years.

“This is why this is challenging for primary care providers,” Dr. LaCross said. “Even urogynecologists who are the specialists that treat prolapse and incontinence have changed how they assess it and the terminology and criteria that they use.”

What hasn’t changed is the substantial negative impact POP can have on quality of life. “This is the second most common reason that women enter nursing homes,” primarily because of urinary incontinence, Dr. Rabin said. “It’s very debilitating, but a lot of it is preventable and a lot is treatable.”

Dr. Rabin estimated that three out of every five women older than 60 and one or two out of every five women younger than 60 experience POP. Prevalence studies vary widely, from nearly a quarter of women to more than half, and racial and ethnic disparities in diagnosis further complicate the statistics.

PCPs therefore have an important role to play in screening for POP. The evidence shows that “patients want their providers to bring this up,” Dr. LaCross said. “They want to talk about it, but they want the provider to ask the questions first.”
 

Causes, Risk Factors, and Symptoms

Many causes contribute to POP, with gravity, aging, childbirth, and menopause at the top of the list.

“As people get older, their pelvic muscles and connective tissue get weaker, and the nerves don’t function as well,” Dr. Rabin said. Meanwhile, the body is losing estrogen, which affects how well the muscles contract and how easily the connective tissue can tear, she said.

With menopause, when baseline estrogen is lower, the tissue integrity is not as supportive as it should be and women are going to be at an increased risk of prolapse, Dr. Nwabuebo said.

POP has a range of risk factors:

• Increasing age, as muscle mass decreases and connective tissue hardens.
• Menopause.
• Vaginal delivery with complications, such as long second-stage labor, instrument-assisted delivery, multiple vaginal lacerations, and improperly repaired episiotomy.
• Multiple vaginal deliveries.
• Birthing large babies.
• Family history of pelvic organ prolapse (genetics can play a role in POP risk).
• Previous pelvic/abdominal surgery, including cesarean delivery and hysterectomy.
• Smoking (largely because of associated coughing).
• Chronic lung conditions that cause a lot of coughing.
• Chronic constipation or irritable bowel syndrome.
• Some types of high-impact activity, such as jogging or marathon running.
• Early menopause, for younger women.
• Repetitive heavy lifting in daily activities, such as occupational lifting (though not necessarily weight lifting as an exercise).
• Higher body mass index.
• Connective tissue disorders, such as joint hypermobility syndrome or Ehlers-Danlos syndrome.

Roger Dmochowski, MD, professor of urology and surgery at Vanderbilt University Medical Center, groups POP symptoms into two groups: anatomic and functional ones. A common anatomic symptom is bulging. “They’ll describe sitting on a ball, feeling like their bladder or something’s falling out, feeling a pressure or a heaviness,” Dr. Dmochowski said.

Functional symptoms can include vaginal dryness, vaginal irritation, painful intercourse, contact of the vaginal tissues with underclothes, and associated urinary symptoms, such as stress incontinence, urge incontinence, and incomplete emptying of the bladder. Dr. Dmochowski noted that women who report urinary incontinence may be at risk for being prescribed a medication without the necessary referral to a specialist for a full gynecologic evaluation.

Two other groups of functional symptoms include bowel-related disorders – primarily fecal incontinence and ongoing constipation – and pelvic pain or discomfort.

There can also be asymptomatic cases. “A lot of women have what we call silent prolapse,” Dr. Dmochowski said. That is, “they have some degree of loss of support to the bladder, vagina, or uterus, but they’re not symptomatic.” These women may be particularly good candidates for pelvic health physical therapy.
 

Screening and Diagnosis

Because many postmenopausal women stop seeing their ob.gyn, it’s often up to their primary care physician to determine whether their patients are experiencing POP symptoms.

“Women sometimes don’t bring this up with their doctor because they think there’s not enough time, or they’ll be laughed at, or their friends told them this is normal,” Dr. Rabin said. But primary care providers are really in a unique position to be able to ask the key symptom questions.

Dr. Rabin recommends a couple of questions to cover all the bases: “Do you leak urine when you cough or sneeze or on the way to the bathroom? Do you notice a bulge coming out of the vagina, or are you bothered by pelvic pressure?”

Dr. Dmochowski offered a single question that can open the conversation to more questions: “Are you bothered by any urinary or bowel or vaginal issues that we should talk about?” He also suggests asking how bothersome the symptoms are, which can help in directing treatment or prevention options. A physical exam can reveal signs of POP as well.

Diagnosis involves a detailed history, a comprehensive physical exam, and assessment with the Pelvic Organ Prolapse Quantification (POP-Q) tool. A urogynecologist can diagnose the type of POP – such as cystocele, rectocele, enterocele, uterine prolapse, or vaginal vault prolapse – and its grade (0-4).
 

Treatment: Physical Therapy, Pessary, and Surgery

No medications can treat prolapse, though some can treat downstream effects, such as hormonal vaginal creams for vaginal dryness and irritation, and medications for urinary incontinence. However, two mistakes PCPs can make are sending someone straight to surgery or prescribing them medication for symptoms without referring them for a diagnostic evaluation, Dr. Rabin said. “You have to have a diagnosis first to know what type of prolapse is there,” she said.

Because there can be long waiting lists for a urogynecologist or urologist, PCPs should also refer their patients to a pelvic health physical therapist (PT) who can help patients begin addressing the symptoms while they await a specialist who can diagnose them.

Though PT is often thought of as preventive, it’s also a conservative first-line intervention for prolapse, Dr. Nwabuebo said. Strong evidence shows pelvic floor muscle training from pelvic health PT can reduce symptoms of prolapse and reduce the severity by one grade in those with a grade 1 or 2 prolapse. Stage 3 is trickier, where PT may or may not be able to shift the symptom presentation, Dr. Nwabeubo said, and stage 4 is usually a surgical candidate.

“If you have a grade 4 prolapse, or the tissues are really visible outside the body, physical therapy and pelvic floor muscle training is not going to elevate that tissue back up into your body, but it can sometimes help with symptoms,” Dr. LaCross said.

The PT conducts a thorough pelvic muscle assessment, discusses lifestyle, and may teach breathing and bracing strategies for lifting, for example.

“A lot of what we’re talking about with pelvic floor therapy is lifestyle modifications,” Dr. Nwabuebo said. “If I have a patient with a history of chronic constipation, it doesn’t matter how much we do pelvic floor exercises; if we don’t manage the constipation issues by addressing their nutrition, then straining when using the bathroom will keep putting pressure on the pelvic floor.”

PTs can also recommend appropriate vaginal weights and dilators to help with pelvic floor strengthening and teach patients how to use them properly.

Even if women ultimately opt for surgery, PT prior to surgery can be beneficial. Dr. Rabin cited three reasons she recommends first-line PT: It may elevate the bladder enough to reduce stress incontinence and thicken the pelvic muscles, it can improve the effectiveness of a pessary or surgery if the woman chooses one of those options, and it can quiet bladder contractions, potentially obviating the need for pharmacologic treatment for overactive bladder.

The next nonsurgical option is a pessary, a device that fits into the vagina to provide support to the tissues displaced by prolapse. There’s a wide range of pessary types: some are short-term, worn only daily, or disposable, while others can be worn longer. Some women can self-insert and remove the pessary, and others may need a clinician to do so. Dr. Dmochowski recommends patients try a pessary to see if it benefits them. About a third of women will find them comfortable enough to wear regularly, but others will feel more sensitive to the pessary’s presence, he said.

One of the newest, most innovative pessary options for women is Gynethotics, which received Food and Drug Administration (FDA) clearance in March, as the first 3D-printed, customizable pessary capable of nearly 10 million configurations based on a person’s body.

Nearly all stage 4 prolapses and most of stage 3 prolapses can be addressed only through transvaginal or transabdominal surgery.

“We tell patients, if you can get 10 years out of your operation, you’re lucky,” Dr. Dmochowski said. A major reason for the short-lived durability is the poor quality of the tissue that needs to be pulled together. Serious complications resulting from use of polypropylene mesh during prolapse surgery led the FDA to halt sales of the devices and recommend discontinuing their use. However, one type of vaginal mesh is still considered safe to use in sacral colpopexy surgery.

Three things can shorten the durability of the surgery, Dr. Dmochowski said: heavy lifting, particularly anything over 30 pounds; chronic coughing, such as in those with chronic lung conditions; and chronic constipation.

Ms. Palm tried a pessary for her grade 3 prolapse with cystocele, rectocele, and enterocele but didn’t feel she had the time to use it regularly, so she opted for surgery. After a week on the couch recovering, she took it easy for another 12 weeks. Since then, she’s dedicated much of her time to educating and supporting women with POP and combating stigma associated with it. The APOPS website that she started has become a valuable resource for PCPs to send patients to, and the forum includes more 27,000 women from around the world.

“We encourage women to share what they’re experiencing. Tell your family, tell your friends, tell the people you work with about it,” Ms. Palm said. But many still feel uncomfortable speaking up, making PCPs’ role even more important.

*This story was updated on May 14, 2024.

Sherrie Palm, a patient advocate in Mukwonago, Wisconsin, learned in her 30s that she needed to educate herself about her own health. So when she discovered a walnut-sized lump coming out of her vagina in her mid-50s, she was stunned when her primary care provider (PCP) told her it was pelvic organ prolapse (POP), where one or more organs descend into the vaginal cavity.

“I was shocked,” Ms. Palm said. After searching online and discovering how prevalent POP was, her shock turned to anger. “I was blown away that it could be this common and I’d never heard of it,” she said. “I knew within 2 weeks that I had to do something to change the status quo.”

Ms. Palm eventually founded the nonprofit Association for Pelvic Organ Prolapse Support, or APOPS, complete with a forum where women can learn about POP and support one another. She said awareness has improved substantially since her diagnosis in 2007, but “we have a long way to go” because POP and vaginal health in general are so stigmatized.

Her website notes that about half of women with incontinence do not seek help, largely because of stigma. “The status quo is that PCPs do not POP screen,” she said. ObGyns may screen but often “because the patient has asked to be screened, they say it’s not that bad, come back and see me in a year, and do your Kegels,” Ms. Palm said.

Doctors who diagnose POP agree that the issue is often off PCPs’ radar.

“Primary care doctors are really in a time crunch, so this is one of the things that may not get addressed,” Jill Rabin, MD, vice chair of education and development in obstetrics and gynecology at Northwell Health in New York, said. Dr. Rabin is also head of urogynecology at Long Island Jewish Medical Center.

Ann Nwabuebo, PT, DPT, owner and founder of Body Connect Physical Therapy in Bethesda, Maryland, said social media has been shifting the attitude that pelvic health is a taboo subject. “It’s empowering people to seek care if they’re not finding physicians who are helping.”

But social media is also a double-edged sword, said Jenny LaCross, PT, DPT, PhD, a physical therapist at MOVE PT in Monroe, Michigan, and a postdoctoral research fellow with Michigan Medicine’s Pelvic Floor Research Group. “Pelvic health in general is talked about a lot more, but there’s also a lot more misinformation,” she said.

Part of that misinformation is the idea that pelvic prolapse is solely about weakness in the pelvic floor when it can also result from a widening of natural openings within the pelvis, Dr. LaCross said. She pointed to the two definitions of pelvic organ prolapse by the International Urogynecologic Consultation and the International Continence Society, both of which have been updated in recent years.

“This is why this is challenging for primary care providers,” Dr. LaCross said. “Even urogynecologists who are the specialists that treat prolapse and incontinence have changed how they assess it and the terminology and criteria that they use.”

What hasn’t changed is the substantial negative impact POP can have on quality of life. “This is the second most common reason that women enter nursing homes,” primarily because of urinary incontinence, Dr. Rabin said. “It’s very debilitating, but a lot of it is preventable and a lot is treatable.”

Dr. Rabin estimated that three out of every five women older than 60 and one or two out of every five women younger than 60 experience POP. Prevalence studies vary widely, from nearly a quarter of women to more than half, and racial and ethnic disparities in diagnosis further complicate the statistics.

PCPs therefore have an important role to play in screening for POP. The evidence shows that “patients want their providers to bring this up,” Dr. LaCross said. “They want to talk about it, but they want the provider to ask the questions first.”
 

Causes, Risk Factors, and Symptoms

Many causes contribute to POP, with gravity, aging, childbirth, and menopause at the top of the list.

“As people get older, their pelvic muscles and connective tissue get weaker, and the nerves don’t function as well,” Dr. Rabin said. Meanwhile, the body is losing estrogen, which affects how well the muscles contract and how easily the connective tissue can tear, she said.

With menopause, when baseline estrogen is lower, the tissue integrity is not as supportive as it should be and women are going to be at an increased risk of prolapse, Dr. Nwabuebo said.

POP has a range of risk factors:

• Increasing age, as muscle mass decreases and connective tissue hardens.
• Menopause.
• Vaginal delivery with complications, such as long second-stage labor, instrument-assisted delivery, multiple vaginal lacerations, and improperly repaired episiotomy.
• Multiple vaginal deliveries.
• Birthing large babies.
• Family history of pelvic organ prolapse (genetics can play a role in POP risk).
• Previous pelvic/abdominal surgery, including cesarean delivery and hysterectomy.
• Smoking (largely because of associated coughing).
• Chronic lung conditions that cause a lot of coughing.
• Chronic constipation or irritable bowel syndrome.
• Some types of high-impact activity, such as jogging or marathon running.
• Early menopause, for younger women.
• Repetitive heavy lifting in daily activities, such as occupational lifting (though not necessarily weight lifting as an exercise).
• Higher body mass index.
• Connective tissue disorders, such as joint hypermobility syndrome or Ehlers-Danlos syndrome.

Roger Dmochowski, MD, professor of urology and surgery at Vanderbilt University Medical Center, groups POP symptoms into two groups: anatomic and functional ones. A common anatomic symptom is bulging. “They’ll describe sitting on a ball, feeling like their bladder or something’s falling out, feeling a pressure or a heaviness,” Dr. Dmochowski said.

Functional symptoms can include vaginal dryness, vaginal irritation, painful intercourse, contact of the vaginal tissues with underclothes, and associated urinary symptoms, such as stress incontinence, urge incontinence, and incomplete emptying of the bladder. Dr. Dmochowski noted that women who report urinary incontinence may be at risk for being prescribed a medication without the necessary referral to a specialist for a full gynecologic evaluation.

Two other groups of functional symptoms include bowel-related disorders – primarily fecal incontinence and ongoing constipation – and pelvic pain or discomfort.

There can also be asymptomatic cases. “A lot of women have what we call silent prolapse,” Dr. Dmochowski said. That is, “they have some degree of loss of support to the bladder, vagina, or uterus, but they’re not symptomatic.” These women may be particularly good candidates for pelvic health physical therapy.
 

Screening and Diagnosis

Because many postmenopausal women stop seeing their ob.gyn, it’s often up to their primary care physician to determine whether their patients are experiencing POP symptoms.

“Women sometimes don’t bring this up with their doctor because they think there’s not enough time, or they’ll be laughed at, or their friends told them this is normal,” Dr. Rabin said. But primary care providers are really in a unique position to be able to ask the key symptom questions.

Dr. Rabin recommends a couple of questions to cover all the bases: “Do you leak urine when you cough or sneeze or on the way to the bathroom? Do you notice a bulge coming out of the vagina, or are you bothered by pelvic pressure?”

Dr. Dmochowski offered a single question that can open the conversation to more questions: “Are you bothered by any urinary or bowel or vaginal issues that we should talk about?” He also suggests asking how bothersome the symptoms are, which can help in directing treatment or prevention options. A physical exam can reveal signs of POP as well.

Diagnosis involves a detailed history, a comprehensive physical exam, and assessment with the Pelvic Organ Prolapse Quantification (POP-Q) tool. A urogynecologist can diagnose the type of POP – such as cystocele, rectocele, enterocele, uterine prolapse, or vaginal vault prolapse – and its grade (0-4).
 

Treatment: Physical Therapy, Pessary, and Surgery

No medications can treat prolapse, though some can treat downstream effects, such as hormonal vaginal creams for vaginal dryness and irritation, and medications for urinary incontinence. However, two mistakes PCPs can make are sending someone straight to surgery or prescribing them medication for symptoms without referring them for a diagnostic evaluation, Dr. Rabin said. “You have to have a diagnosis first to know what type of prolapse is there,” she said.

Because there can be long waiting lists for a urogynecologist or urologist, PCPs should also refer their patients to a pelvic health physical therapist (PT) who can help patients begin addressing the symptoms while they await a specialist who can diagnose them.

Though PT is often thought of as preventive, it’s also a conservative first-line intervention for prolapse, Dr. Nwabuebo said. Strong evidence shows pelvic floor muscle training from pelvic health PT can reduce symptoms of prolapse and reduce the severity by one grade in those with a grade 1 or 2 prolapse. Stage 3 is trickier, where PT may or may not be able to shift the symptom presentation, Dr. Nwabeubo said, and stage 4 is usually a surgical candidate.

“If you have a grade 4 prolapse, or the tissues are really visible outside the body, physical therapy and pelvic floor muscle training is not going to elevate that tissue back up into your body, but it can sometimes help with symptoms,” Dr. LaCross said.

The PT conducts a thorough pelvic muscle assessment, discusses lifestyle, and may teach breathing and bracing strategies for lifting, for example.

“A lot of what we’re talking about with pelvic floor therapy is lifestyle modifications,” Dr. Nwabuebo said. “If I have a patient with a history of chronic constipation, it doesn’t matter how much we do pelvic floor exercises; if we don’t manage the constipation issues by addressing their nutrition, then straining when using the bathroom will keep putting pressure on the pelvic floor.”

PTs can also recommend appropriate vaginal weights and dilators to help with pelvic floor strengthening and teach patients how to use them properly.

Even if women ultimately opt for surgery, PT prior to surgery can be beneficial. Dr. Rabin cited three reasons she recommends first-line PT: It may elevate the bladder enough to reduce stress incontinence and thicken the pelvic muscles, it can improve the effectiveness of a pessary or surgery if the woman chooses one of those options, and it can quiet bladder contractions, potentially obviating the need for pharmacologic treatment for overactive bladder.

The next nonsurgical option is a pessary, a device that fits into the vagina to provide support to the tissues displaced by prolapse. There’s a wide range of pessary types: some are short-term, worn only daily, or disposable, while others can be worn longer. Some women can self-insert and remove the pessary, and others may need a clinician to do so. Dr. Dmochowski recommends patients try a pessary to see if it benefits them. About a third of women will find them comfortable enough to wear regularly, but others will feel more sensitive to the pessary’s presence, he said.

One of the newest, most innovative pessary options for women is Gynethotics, which received Food and Drug Administration (FDA) clearance in March, as the first 3D-printed, customizable pessary capable of nearly 10 million configurations based on a person’s body.

Nearly all stage 4 prolapses and most of stage 3 prolapses can be addressed only through transvaginal or transabdominal surgery.

“We tell patients, if you can get 10 years out of your operation, you’re lucky,” Dr. Dmochowski said. A major reason for the short-lived durability is the poor quality of the tissue that needs to be pulled together. Serious complications resulting from use of polypropylene mesh during prolapse surgery led the FDA to halt sales of the devices and recommend discontinuing their use. However, one type of vaginal mesh is still considered safe to use in sacral colpopexy surgery.

Three things can shorten the durability of the surgery, Dr. Dmochowski said: heavy lifting, particularly anything over 30 pounds; chronic coughing, such as in those with chronic lung conditions; and chronic constipation.

Ms. Palm tried a pessary for her grade 3 prolapse with cystocele, rectocele, and enterocele but didn’t feel she had the time to use it regularly, so she opted for surgery. After a week on the couch recovering, she took it easy for another 12 weeks. Since then, she’s dedicated much of her time to educating and supporting women with POP and combating stigma associated with it. The APOPS website that she started has become a valuable resource for PCPs to send patients to, and the forum includes more 27,000 women from around the world.

“We encourage women to share what they’re experiencing. Tell your family, tell your friends, tell the people you work with about it,” Ms. Palm said. But many still feel uncomfortable speaking up, making PCPs’ role even more important.

*This story was updated on May 14, 2024.

Sherrie Palm, a patient advocate in Mukwonago, Wisconsin, learned in her 30s that she needed to educate herself about her own health. So when she discovered a walnut-sized lump coming out of her vagina in her mid-50s, she was stunned when her primary care provider (PCP) told her it was pelvic organ prolapse (POP), where one or more organs descend into the vaginal cavity.

“I was shocked,” Ms. Palm said. After searching online and discovering how prevalent POP was, her shock turned to anger. “I was blown away that it could be this common and I’d never heard of it,” she said. “I knew within 2 weeks that I had to do something to change the status quo.”

Ms. Palm eventually founded the nonprofit Association for Pelvic Organ Prolapse Support, or APOPS, complete with a forum where women can learn about POP and support one another. She said awareness has improved substantially since her diagnosis in 2007, but “we have a long way to go” because POP and vaginal health in general are so stigmatized.

Her website notes that about half of women with incontinence do not seek help, largely because of stigma. “The status quo is that PCPs do not POP screen,” she said. ObGyns may screen but often “because the patient has asked to be screened, they say it’s not that bad, come back and see me in a year, and do your Kegels,” Ms. Palm said.

Doctors who diagnose POP agree that the issue is often off PCPs’ radar.

“Primary care doctors are really in a time crunch, so this is one of the things that may not get addressed,” Jill Rabin, MD, vice chair of education and development in obstetrics and gynecology at Northwell Health in New York, said. Dr. Rabin is also head of urogynecology at Long Island Jewish Medical Center.

Ann Nwabuebo, PT, DPT, owner and founder of Body Connect Physical Therapy in Bethesda, Maryland, said social media has been shifting the attitude that pelvic health is a taboo subject. “It’s empowering people to seek care if they’re not finding physicians who are helping.”

But social media is also a double-edged sword, said Jenny LaCross, PT, DPT, PhD, a physical therapist at MOVE PT in Monroe, Michigan, and a postdoctoral research fellow with Michigan Medicine’s Pelvic Floor Research Group. “Pelvic health in general is talked about a lot more, but there’s also a lot more misinformation,” she said.

Part of that misinformation is the idea that pelvic prolapse is solely about weakness in the pelvic floor when it can also result from a widening of natural openings within the pelvis, Dr. LaCross said. She pointed to the two definitions of pelvic organ prolapse by the International Urogynecologic Consultation and the International Continence Society, both of which have been updated in recent years.

“This is why this is challenging for primary care providers,” Dr. LaCross said. “Even urogynecologists who are the specialists that treat prolapse and incontinence have changed how they assess it and the terminology and criteria that they use.”

What hasn’t changed is the substantial negative impact POP can have on quality of life. “This is the second most common reason that women enter nursing homes,” primarily because of urinary incontinence, Dr. Rabin said. “It’s very debilitating, but a lot of it is preventable and a lot is treatable.”

Dr. Rabin estimated that three out of every five women older than 60 and one or two out of every five women younger than 60 experience POP. Prevalence studies vary widely, from nearly a quarter of women to more than half, and racial and ethnic disparities in diagnosis further complicate the statistics.

PCPs therefore have an important role to play in screening for POP. The evidence shows that “patients want their providers to bring this up,” Dr. LaCross said. “They want to talk about it, but they want the provider to ask the questions first.”
 

Causes, Risk Factors, and Symptoms

Many causes contribute to POP, with gravity, aging, childbirth, and menopause at the top of the list.

“As people get older, their pelvic muscles and connective tissue get weaker, and the nerves don’t function as well,” Dr. Rabin said. Meanwhile, the body is losing estrogen, which affects how well the muscles contract and how easily the connective tissue can tear, she said.

With menopause, when baseline estrogen is lower, the tissue integrity is not as supportive as it should be and women are going to be at an increased risk of prolapse, Dr. Nwabuebo said.

POP has a range of risk factors:

• Increasing age, as muscle mass decreases and connective tissue hardens.
• Menopause.
• Vaginal delivery with complications, such as long second-stage labor, instrument-assisted delivery, multiple vaginal lacerations, and improperly repaired episiotomy.
• Multiple vaginal deliveries.
• Birthing large babies.
• Family history of pelvic organ prolapse (genetics can play a role in POP risk).
• Previous pelvic/abdominal surgery, including cesarean delivery and hysterectomy.
• Smoking (largely because of associated coughing).
• Chronic lung conditions that cause a lot of coughing.
• Chronic constipation or irritable bowel syndrome.
• Some types of high-impact activity, such as jogging or marathon running.
• Early menopause, for younger women.
• Repetitive heavy lifting in daily activities, such as occupational lifting (though not necessarily weight lifting as an exercise).
• Higher body mass index.
• Connective tissue disorders, such as joint hypermobility syndrome or Ehlers-Danlos syndrome.

Roger Dmochowski, MD, professor of urology and surgery at Vanderbilt University Medical Center, groups POP symptoms into two groups: anatomic and functional ones. A common anatomic symptom is bulging. “They’ll describe sitting on a ball, feeling like their bladder or something’s falling out, feeling a pressure or a heaviness,” Dr. Dmochowski said.

Functional symptoms can include vaginal dryness, vaginal irritation, painful intercourse, contact of the vaginal tissues with underclothes, and associated urinary symptoms, such as stress incontinence, urge incontinence, and incomplete emptying of the bladder. Dr. Dmochowski noted that women who report urinary incontinence may be at risk for being prescribed a medication without the necessary referral to a specialist for a full gynecologic evaluation.

Two other groups of functional symptoms include bowel-related disorders – primarily fecal incontinence and ongoing constipation – and pelvic pain or discomfort.

There can also be asymptomatic cases. “A lot of women have what we call silent prolapse,” Dr. Dmochowski said. That is, “they have some degree of loss of support to the bladder, vagina, or uterus, but they’re not symptomatic.” These women may be particularly good candidates for pelvic health physical therapy.
 

Screening and Diagnosis

Because many postmenopausal women stop seeing their ob.gyn, it’s often up to their primary care physician to determine whether their patients are experiencing POP symptoms.

“Women sometimes don’t bring this up with their doctor because they think there’s not enough time, or they’ll be laughed at, or their friends told them this is normal,” Dr. Rabin said. But primary care providers are really in a unique position to be able to ask the key symptom questions.

Dr. Rabin recommends a couple of questions to cover all the bases: “Do you leak urine when you cough or sneeze or on the way to the bathroom? Do you notice a bulge coming out of the vagina, or are you bothered by pelvic pressure?”

Dr. Dmochowski offered a single question that can open the conversation to more questions: “Are you bothered by any urinary or bowel or vaginal issues that we should talk about?” He also suggests asking how bothersome the symptoms are, which can help in directing treatment or prevention options. A physical exam can reveal signs of POP as well.

Diagnosis involves a detailed history, a comprehensive physical exam, and assessment with the Pelvic Organ Prolapse Quantification (POP-Q) tool. A urogynecologist can diagnose the type of POP – such as cystocele, rectocele, enterocele, uterine prolapse, or vaginal vault prolapse – and its grade (0-4).
 

Treatment: Physical Therapy, Pessary, and Surgery

No medications can treat prolapse, though some can treat downstream effects, such as hormonal vaginal creams for vaginal dryness and irritation, and medications for urinary incontinence. However, two mistakes PCPs can make are sending someone straight to surgery or prescribing them medication for symptoms without referring them for a diagnostic evaluation, Dr. Rabin said. “You have to have a diagnosis first to know what type of prolapse is there,” she said.

Because there can be long waiting lists for a urogynecologist or urologist, PCPs should also refer their patients to a pelvic health physical therapist (PT) who can help patients begin addressing the symptoms while they await a specialist who can diagnose them.

Though PT is often thought of as preventive, it’s also a conservative first-line intervention for prolapse, Dr. Nwabuebo said. Strong evidence shows pelvic floor muscle training from pelvic health PT can reduce symptoms of prolapse and reduce the severity by one grade in those with a grade 1 or 2 prolapse. Stage 3 is trickier, where PT may or may not be able to shift the symptom presentation, Dr. Nwabeubo said, and stage 4 is usually a surgical candidate.

“If you have a grade 4 prolapse, or the tissues are really visible outside the body, physical therapy and pelvic floor muscle training is not going to elevate that tissue back up into your body, but it can sometimes help with symptoms,” Dr. LaCross said.

The PT conducts a thorough pelvic muscle assessment, discusses lifestyle, and may teach breathing and bracing strategies for lifting, for example.

“A lot of what we’re talking about with pelvic floor therapy is lifestyle modifications,” Dr. Nwabuebo said. “If I have a patient with a history of chronic constipation, it doesn’t matter how much we do pelvic floor exercises; if we don’t manage the constipation issues by addressing their nutrition, then straining when using the bathroom will keep putting pressure on the pelvic floor.”

PTs can also recommend appropriate vaginal weights and dilators to help with pelvic floor strengthening and teach patients how to use them properly.

Even if women ultimately opt for surgery, PT prior to surgery can be beneficial. Dr. Rabin cited three reasons she recommends first-line PT: It may elevate the bladder enough to reduce stress incontinence and thicken the pelvic muscles, it can improve the effectiveness of a pessary or surgery if the woman chooses one of those options, and it can quiet bladder contractions, potentially obviating the need for pharmacologic treatment for overactive bladder.

The next nonsurgical option is a pessary, a device that fits into the vagina to provide support to the tissues displaced by prolapse. There’s a wide range of pessary types: some are short-term, worn only daily, or disposable, while others can be worn longer. Some women can self-insert and remove the pessary, and others may need a clinician to do so. Dr. Dmochowski recommends patients try a pessary to see if it benefits them. About a third of women will find them comfortable enough to wear regularly, but others will feel more sensitive to the pessary’s presence, he said.

One of the newest, most innovative pessary options for women is Gynethotics, which received Food and Drug Administration (FDA) clearance in March, as the first 3D-printed, customizable pessary capable of nearly 10 million configurations based on a person’s body.

Nearly all stage 4 prolapses and most of stage 3 prolapses can be addressed only through transvaginal or transabdominal surgery.

“We tell patients, if you can get 10 years out of your operation, you’re lucky,” Dr. Dmochowski said. A major reason for the short-lived durability is the poor quality of the tissue that needs to be pulled together. Serious complications resulting from use of polypropylene mesh during prolapse surgery led the FDA to halt sales of the devices and recommend discontinuing their use. However, one type of vaginal mesh is still considered safe to use in sacral colpopexy surgery.

Three things can shorten the durability of the surgery, Dr. Dmochowski said: heavy lifting, particularly anything over 30 pounds; chronic coughing, such as in those with chronic lung conditions; and chronic constipation.

Ms. Palm tried a pessary for her grade 3 prolapse with cystocele, rectocele, and enterocele but didn’t feel she had the time to use it regularly, so she opted for surgery. After a week on the couch recovering, she took it easy for another 12 weeks. Since then, she’s dedicated much of her time to educating and supporting women with POP and combating stigma associated with it. The APOPS website that she started has become a valuable resource for PCPs to send patients to, and the forum includes more 27,000 women from around the world.

“We encourage women to share what they’re experiencing. Tell your family, tell your friends, tell the people you work with about it,” Ms. Palm said. But many still feel uncomfortable speaking up, making PCPs’ role even more important.

*This story was updated on May 14, 2024.

As three federal agencies investigate how private equity ownership and consolidation of healthcare organizations affects patient care and costs, physicians are giving them an earful.

“Before I retired, I could already see the damage private equity was doing to hospitals and medical practices. Well-regarded physician groups were being bought and the respected doctors and staff forced out to squeeze out profit for the buyers. Hospital-based physicians were being hit especially hard,” wrote Rhonda Wright, MD, of Brookhaven, Georgia. 

“Now, the rot is setting in for emergency rooms. One in four ERs is now (under-)staffed by private equity firms. This is leading to longer wait times, deterioration in patient care, and higher bills,” Dr. Wright continued. “Private equity takeover of medicine must be stopped. All such deals should be strictly regulated and should be heavily scrutinized, if not barred altogether. Our health depends upon it!”

The federal government is accepting public comments like Dr. Wright’s through June 5 and has even set up a website (healthycompetition.gov) to make it easier to file complaints against health organizations possibly violating antitrust laws.

The US Department of Justice’s Antitrust Division, the Federal Trade Commission (FTC), and the Department of Health and Human Services want to hear from physicians and the public about how private equity firms’ investments in healthcare entities, such as hospitals, nursing homes, or specialty service providers, affect patients and healthcare workers. The investigation will also evaluate how market pricing, competition, and referral patterns change when practices and hospitals are acquired by health systems or insurers.

Maintaining competition in the provider and payer markets benefits healthcare workers through higher pay, while patients can access quality care at lower prices, the joint request for information said. However, consolidation and mergers — potentially driven by private equity’s entry into the market — can diminish these benefits.

Investigating private equity and consolidation in medicine is part of the Biden Administration’s focus on lowering medical and prescription drug costs and strengthening competition in healthcare. The FTC’s vote last week to ban noncompete agreements, which business groups have vowed to challenge in court, falls under the same initiative.

Alexandra Nicole Thran, MD, FACEP, president of the Vermont Chapter of the American College of Emergency Physicians, said that the private equity business model is problematic because it ties physicians’ wages to patient satisfaction and the number of patients they see per hour. 

A Connecticut primary care physician expressed similar sentiments. “Physicians are being forced into a system where corporations provide financial incentives and punitive policies to direct healthcare decisions towards a profitable aim,” said Eric Schwaber, MD. 

While a majority of comments criticized the role of private equity and consolidation, some reflected a more positive view. 

“Private equity helps make healthcare more efficient and effective. It brings needed operational and managerial expertise to allow for better patient care,” said Reenie Abraham, MD, an associate professor in the Department of Internal Medicine at University of Texas Southwestern Medical Center, Dallas. The University of Texas is facing a lawsuit involving the liability status of its physicians who work for a private equity-backed hospital partly owned by the university.

Several public comments point to the increasing market influence UnitedHealth Group (UHG) and other payers have obtained through recent acquisitions. Retired emergency room physician Scott Davis, MD, said that the “astronomical” rate of burnout among providers has been exacerbated by “the economic takeover of the healthcare system by…United Healthcare [and] private equity groups who put profits over anything else.”  

The healthcare conglomerate employs approximately 10% of active US physicians, including many through its subsidiary, Optum Health, which provides primary, urgent, and surgical care. UHG has also invested heavily in acquiring physician practices to advance its value-based care model.

“If a publicly traded private insurance or private equity company is interested in their short-term quarterly profits or stock price, there is little interest in the…effective management of chronic disease, other than that which fulfills a ‘value-based’ metric,” wrote Kenneth Dolkart, MD, FACP, clinical assistant professor at the Dartmouth Geisel School of Medicine in Hanover, New Hampshire. 

Sarah Ealy, a revenue cycle professional, commented that payers like UHG have outsized bargaining power when negotiating rates with providers. “In many states, United Healthcare and its subsidiaries pay a lower reimbursement rate than state Medicaid plans — these rates are nearly 50% of the breakeven per-visit rate that practices need to keep the lights on.”

Another comment ties the recent cyberattack on UHG-owned Change Healthcare to private equity ownership and “healthcare behemoths buying up practices and data.”

“The ramrodding of consolidation and private oversight with little to no barriers to foreign intrusions…is a testament to how ill prepared [the] US market is to private equity healthcare takeovers,” said SW Dermatology Practice LLC. 

The agencies request comments from all health market participants, including physicians, nurses, employers, administrators, and patients.

A version of this article first appeared on Medscape.com.

As three federal agencies investigate how private equity ownership and consolidation of healthcare organizations affects patient care and costs, physicians are giving them an earful.

“Before I retired, I could already see the damage private equity was doing to hospitals and medical practices. Well-regarded physician groups were being bought and the respected doctors and staff forced out to squeeze out profit for the buyers. Hospital-based physicians were being hit especially hard,” wrote Rhonda Wright, MD, of Brookhaven, Georgia. 

“Now, the rot is setting in for emergency rooms. One in four ERs is now (under-)staffed by private equity firms. This is leading to longer wait times, deterioration in patient care, and higher bills,” Dr. Wright continued. “Private equity takeover of medicine must be stopped. All such deals should be strictly regulated and should be heavily scrutinized, if not barred altogether. Our health depends upon it!”

The federal government is accepting public comments like Dr. Wright’s through June 5 and has even set up a website (healthycompetition.gov) to make it easier to file complaints against health organizations possibly violating antitrust laws.

The US Department of Justice’s Antitrust Division, the Federal Trade Commission (FTC), and the Department of Health and Human Services want to hear from physicians and the public about how private equity firms’ investments in healthcare entities, such as hospitals, nursing homes, or specialty service providers, affect patients and healthcare workers. The investigation will also evaluate how market pricing, competition, and referral patterns change when practices and hospitals are acquired by health systems or insurers.

Maintaining competition in the provider and payer markets benefits healthcare workers through higher pay, while patients can access quality care at lower prices, the joint request for information said. However, consolidation and mergers — potentially driven by private equity’s entry into the market — can diminish these benefits.

Investigating private equity and consolidation in medicine is part of the Biden Administration’s focus on lowering medical and prescription drug costs and strengthening competition in healthcare. The FTC’s vote last week to ban noncompete agreements, which business groups have vowed to challenge in court, falls under the same initiative.

Alexandra Nicole Thran, MD, FACEP, president of the Vermont Chapter of the American College of Emergency Physicians, said that the private equity business model is problematic because it ties physicians’ wages to patient satisfaction and the number of patients they see per hour. 

A Connecticut primary care physician expressed similar sentiments. “Physicians are being forced into a system where corporations provide financial incentives and punitive policies to direct healthcare decisions towards a profitable aim,” said Eric Schwaber, MD. 

While a majority of comments criticized the role of private equity and consolidation, some reflected a more positive view. 

“Private equity helps make healthcare more efficient and effective. It brings needed operational and managerial expertise to allow for better patient care,” said Reenie Abraham, MD, an associate professor in the Department of Internal Medicine at University of Texas Southwestern Medical Center, Dallas. The University of Texas is facing a lawsuit involving the liability status of its physicians who work for a private equity-backed hospital partly owned by the university.

Several public comments point to the increasing market influence UnitedHealth Group (UHG) and other payers have obtained through recent acquisitions. Retired emergency room physician Scott Davis, MD, said that the “astronomical” rate of burnout among providers has been exacerbated by “the economic takeover of the healthcare system by…United Healthcare [and] private equity groups who put profits over anything else.”  

The healthcare conglomerate employs approximately 10% of active US physicians, including many through its subsidiary, Optum Health, which provides primary, urgent, and surgical care. UHG has also invested heavily in acquiring physician practices to advance its value-based care model.

“If a publicly traded private insurance or private equity company is interested in their short-term quarterly profits or stock price, there is little interest in the…effective management of chronic disease, other than that which fulfills a ‘value-based’ metric,” wrote Kenneth Dolkart, MD, FACP, clinical assistant professor at the Dartmouth Geisel School of Medicine in Hanover, New Hampshire. 

Sarah Ealy, a revenue cycle professional, commented that payers like UHG have outsized bargaining power when negotiating rates with providers. “In many states, United Healthcare and its subsidiaries pay a lower reimbursement rate than state Medicaid plans — these rates are nearly 50% of the breakeven per-visit rate that practices need to keep the lights on.”

Another comment ties the recent cyberattack on UHG-owned Change Healthcare to private equity ownership and “healthcare behemoths buying up practices and data.”

“The ramrodding of consolidation and private oversight with little to no barriers to foreign intrusions…is a testament to how ill prepared [the] US market is to private equity healthcare takeovers,” said SW Dermatology Practice LLC. 

The agencies request comments from all health market participants, including physicians, nurses, employers, administrators, and patients.

A version of this article first appeared on Medscape.com.

As three federal agencies investigate how private equity ownership and consolidation of healthcare organizations affects patient care and costs, physicians are giving them an earful.

“Before I retired, I could already see the damage private equity was doing to hospitals and medical practices. Well-regarded physician groups were being bought and the respected doctors and staff forced out to squeeze out profit for the buyers. Hospital-based physicians were being hit especially hard,” wrote Rhonda Wright, MD, of Brookhaven, Georgia. 

“Now, the rot is setting in for emergency rooms. One in four ERs is now (under-)staffed by private equity firms. This is leading to longer wait times, deterioration in patient care, and higher bills,” Dr. Wright continued. “Private equity takeover of medicine must be stopped. All such deals should be strictly regulated and should be heavily scrutinized, if not barred altogether. Our health depends upon it!”

The federal government is accepting public comments like Dr. Wright’s through June 5 and has even set up a website (healthycompetition.gov) to make it easier to file complaints against health organizations possibly violating antitrust laws.

The US Department of Justice’s Antitrust Division, the Federal Trade Commission (FTC), and the Department of Health and Human Services want to hear from physicians and the public about how private equity firms’ investments in healthcare entities, such as hospitals, nursing homes, or specialty service providers, affect patients and healthcare workers. The investigation will also evaluate how market pricing, competition, and referral patterns change when practices and hospitals are acquired by health systems or insurers.

Maintaining competition in the provider and payer markets benefits healthcare workers through higher pay, while patients can access quality care at lower prices, the joint request for information said. However, consolidation and mergers — potentially driven by private equity’s entry into the market — can diminish these benefits.

Investigating private equity and consolidation in medicine is part of the Biden Administration’s focus on lowering medical and prescription drug costs and strengthening competition in healthcare. The FTC’s vote last week to ban noncompete agreements, which business groups have vowed to challenge in court, falls under the same initiative.

Alexandra Nicole Thran, MD, FACEP, president of the Vermont Chapter of the American College of Emergency Physicians, said that the private equity business model is problematic because it ties physicians’ wages to patient satisfaction and the number of patients they see per hour. 

A Connecticut primary care physician expressed similar sentiments. “Physicians are being forced into a system where corporations provide financial incentives and punitive policies to direct healthcare decisions towards a profitable aim,” said Eric Schwaber, MD. 

While a majority of comments criticized the role of private equity and consolidation, some reflected a more positive view. 

“Private equity helps make healthcare more efficient and effective. It brings needed operational and managerial expertise to allow for better patient care,” said Reenie Abraham, MD, an associate professor in the Department of Internal Medicine at University of Texas Southwestern Medical Center, Dallas. The University of Texas is facing a lawsuit involving the liability status of its physicians who work for a private equity-backed hospital partly owned by the university.

Several public comments point to the increasing market influence UnitedHealth Group (UHG) and other payers have obtained through recent acquisitions. Retired emergency room physician Scott Davis, MD, said that the “astronomical” rate of burnout among providers has been exacerbated by “the economic takeover of the healthcare system by…United Healthcare [and] private equity groups who put profits over anything else.”  

The healthcare conglomerate employs approximately 10% of active US physicians, including many through its subsidiary, Optum Health, which provides primary, urgent, and surgical care. UHG has also invested heavily in acquiring physician practices to advance its value-based care model.

“If a publicly traded private insurance or private equity company is interested in their short-term quarterly profits or stock price, there is little interest in the…effective management of chronic disease, other than that which fulfills a ‘value-based’ metric,” wrote Kenneth Dolkart, MD, FACP, clinical assistant professor at the Dartmouth Geisel School of Medicine in Hanover, New Hampshire. 

Sarah Ealy, a revenue cycle professional, commented that payers like UHG have outsized bargaining power when negotiating rates with providers. “In many states, United Healthcare and its subsidiaries pay a lower reimbursement rate than state Medicaid plans — these rates are nearly 50% of the breakeven per-visit rate that practices need to keep the lights on.”

Another comment ties the recent cyberattack on UHG-owned Change Healthcare to private equity ownership and “healthcare behemoths buying up practices and data.”

“The ramrodding of consolidation and private oversight with little to no barriers to foreign intrusions…is a testament to how ill prepared [the] US market is to private equity healthcare takeovers,” said SW Dermatology Practice LLC. 

The agencies request comments from all health market participants, including physicians, nurses, employers, administrators, and patients.

A version of this article first appeared on Medscape.com.

Health-related social needs and medical financial hardship are associated with increased risk of mortality in adult cancer survivors, based on data from more than 10,000 individuals.

Little is known about the specific association between health-related social needs (HRSNs) and mortality risk even though HRSNs, defined as challenges in affording food, housing, and other necessities of daily living, are potential challenges for cancer survivors, wrote Zhiyuan Zheng, PhD, of the American Cancer Society, Atlanta, and colleagues.

A 2020 study by Dr. Zheng and colleagues published in the Journal of the National Comprehensive Cancer Network (NCCN) showed that food insecurity and financial worries had a negative impact on cancer survivorship. In the new study, published in Cancer, the researchers identified cancer survivors using the 2013-2018 National Health Interview Survey (NHIS) and the NHIS Mortality File through December 31, 2019. The researchers examined mortality using the data from the Centers for Disease Control and Prevention’s National Death Index (NDI) through December 31, 2019, which links to the National Health Interview Survey Data used in the study.

Individuals’ HRSNs were categorized into three groups: severe, moderate, and minor/none. HRSNs included food insecurity and nonmedical financial concerns, such as housing costs (rent, mortgage). Medical financial hardship included material, psychological, and behavioral domains and was divided into three groups: 2-3 domains, 1 domain, or 0 domains.
 

What Are the Potential Financial Implications of this Research?

The high costs of cancer care often cause medical financial hardships for cancer survivors, and expenses also may cause psychological distress and nonmedical financial hardship as survivors try to make ends meet while facing medical bills, wrote Dr. Zheng and colleagues.

Policy makers are increasingly interested in adding HRSNs to insurance coverage; recent guidance from the Centers for Medicare & Medicaid Services (CMS) allows individual states to apply to provide nutrition and housing supports through state Medicaid programs, according to authors of a 2023 article published in JAMA Health Forum.

The new study adds to the understanding of how HRSNs impact people with cancer by examining the association with mortality risk, Yelak Biru, MSc, president and chief executive officer of the International Myeloma Foundation, said in an interview.

“This is a key area of study for addressing the disparities in treatments and outcomes that result in inequities,” said Mr. Biru, a patient advocate and multiple myeloma survivor who was not involved in the study.
 

What Does the New Study Show?

The new study characterized HRSNs in 5,855 adult cancer survivors aged 18-64 years and 5,918 aged 65-79 years. In the 18- to 64-year-old group, 25.5% reported moderate levels of HRSNs, and 18.3% reported severe HRSNs. In patients aged 65-79 years, 15.6% and 6.6% reported moderate HRSNs and severe HRSNs, respectively.

Severe HRSN was significantly associated with higher mortality risk in an adjusted analysis in patients aged 18-64 years (hazard ratio 2.00, P < .001).

Among adults aged 65-79 years, severe HRSN was not associated with higher mortality risk; however, in this older age group, those with 2-3 domains of medical financial hardship had significantly increased mortality risk compared with adults aged 65-79 years with zero domains of medical financial hardship (HR 1.58, P = .007).

Although the findings that HRSNs were associated with increased mortality risk, especially in the younger group, were not surprising, they serve as a call to action to address how HRSNs are contributing to cancer mortality, Mr. Biru said in an interview. “HRSNs, like food or housing insecurity, can lead to patients being unable to undergo the best treatment approach for their cancer,” he said.
 

What Are the Limitations and Research Gaps?

The study findings were limited by several factors including the use of self-reports to measure medical financial hardship, food insecurity, and nonmedical financial concerns in the NHIS, the researchers wrote in their discussion. More research with longer follow-up time beyond 1-5 years is needed, wrote Dr. Zheng and colleagues.

Studies also are needed to illustrate how patient navigation can help prevent patients from falling through the cracks with regard to social needs and financial hardships, Mr. Biru told this news organization.

Other areas for research include how addressing social needs affects health outcomes and whether programs designed to address social needs are effective, he said.

“Finally, qualitative research is needed to capture the lived experiences of cancer survivors facing these challenges. This knowledge can inform the development of more patient-centered interventions and policies that effectively address the social determinants of health and improve overall outcomes for all cancer survivors,” Mr. Biru said.
 

What Is the Takeaway Message for Clinicians?

HRSNs and financial hardship are significantly associated with increased risk of mortality in adult cancer survivors, Dr. Zheng and colleagues concluded. Looking ahead, comprehensive assessment of HRSNs and financial hardship may help clinicians connect patients with relevant services to mitigate the social and financial impacts of cancer, they wrote.

“The takeaway message for oncologists in practice is that addressing [HRSNs] and financial hardship is crucial for providing comprehensive and equitable cancer care,” Mr. Biru said during his interview.

“The impact of social determinants of health on cancer outcomes cannot be ignored, and oncologists play a vital role in identifying and addressing these needs,” he said. Sensitive, discussion-based screenings are needed to identify core needs such as food and transportation, but clinicians also can consider broader social factors and work with a team to connect patients to appropriate resources, he added.

“By recognizing the importance of HRSN screening and taking proactive steps to address these needs, oncologists can contribute to improving health outcomes, reducing healthcare disparities, and providing more equitable cancer care for their patients,” he said.
 

What Other Guidance Is Available?

“High-quality cancer care requires treating the whole person; measuring and addressing anything in their life that could result in poorer health outcomes is a key component of comprehensive care,” Mr. Biru emphasized.

In September 2023, the National Comprehensive Cancer Network (NCCN) convened a working group cochaired by Mr. Biru that developed recommendations for how oncology practices should routinely measure HRSNs (NCCN.org/social-needs).

“The working group proposed that every cancer patient be assessed for food, transportation access, and financial and housing security at least once a year, and be reassessed at every care transition point as well,” Mr. Biru said. Such screenings should include follow-up to connect patients with services to address any HRSNs they are experiencing, he added.

Lead author Dr. Zheng is employed by the American Cancer Society, which as a nonprofit receives funds from the public through fundraising and contributions, as well as some support from corporations and industry to support its mission programs and services. Mr. Biru had no financial conflicts to disclose.

Health-related social needs and medical financial hardship are associated with increased risk of mortality in adult cancer survivors, based on data from more than 10,000 individuals.

Little is known about the specific association between health-related social needs (HRSNs) and mortality risk even though HRSNs, defined as challenges in affording food, housing, and other necessities of daily living, are potential challenges for cancer survivors, wrote Zhiyuan Zheng, PhD, of the American Cancer Society, Atlanta, and colleagues.

A 2020 study by Dr. Zheng and colleagues published in the Journal of the National Comprehensive Cancer Network (NCCN) showed that food insecurity and financial worries had a negative impact on cancer survivorship. In the new study, published in Cancer, the researchers identified cancer survivors using the 2013-2018 National Health Interview Survey (NHIS) and the NHIS Mortality File through December 31, 2019. The researchers examined mortality using the data from the Centers for Disease Control and Prevention’s National Death Index (NDI) through December 31, 2019, which links to the National Health Interview Survey Data used in the study.

Individuals’ HRSNs were categorized into three groups: severe, moderate, and minor/none. HRSNs included food insecurity and nonmedical financial concerns, such as housing costs (rent, mortgage). Medical financial hardship included material, psychological, and behavioral domains and was divided into three groups: 2-3 domains, 1 domain, or 0 domains.
 

What Are the Potential Financial Implications of this Research?

The high costs of cancer care often cause medical financial hardships for cancer survivors, and expenses also may cause psychological distress and nonmedical financial hardship as survivors try to make ends meet while facing medical bills, wrote Dr. Zheng and colleagues.

Policy makers are increasingly interested in adding HRSNs to insurance coverage; recent guidance from the Centers for Medicare & Medicaid Services (CMS) allows individual states to apply to provide nutrition and housing supports through state Medicaid programs, according to authors of a 2023 article published in JAMA Health Forum.

The new study adds to the understanding of how HRSNs impact people with cancer by examining the association with mortality risk, Yelak Biru, MSc, president and chief executive officer of the International Myeloma Foundation, said in an interview.

“This is a key area of study for addressing the disparities in treatments and outcomes that result in inequities,” said Mr. Biru, a patient advocate and multiple myeloma survivor who was not involved in the study.
 

What Does the New Study Show?

The new study characterized HRSNs in 5,855 adult cancer survivors aged 18-64 years and 5,918 aged 65-79 years. In the 18- to 64-year-old group, 25.5% reported moderate levels of HRSNs, and 18.3% reported severe HRSNs. In patients aged 65-79 years, 15.6% and 6.6% reported moderate HRSNs and severe HRSNs, respectively.

Severe HRSN was significantly associated with higher mortality risk in an adjusted analysis in patients aged 18-64 years (hazard ratio 2.00, P < .001).

Among adults aged 65-79 years, severe HRSN was not associated with higher mortality risk; however, in this older age group, those with 2-3 domains of medical financial hardship had significantly increased mortality risk compared with adults aged 65-79 years with zero domains of medical financial hardship (HR 1.58, P = .007).

Although the findings that HRSNs were associated with increased mortality risk, especially in the younger group, were not surprising, they serve as a call to action to address how HRSNs are contributing to cancer mortality, Mr. Biru said in an interview. “HRSNs, like food or housing insecurity, can lead to patients being unable to undergo the best treatment approach for their cancer,” he said.
 

What Are the Limitations and Research Gaps?

The study findings were limited by several factors including the use of self-reports to measure medical financial hardship, food insecurity, and nonmedical financial concerns in the NHIS, the researchers wrote in their discussion. More research with longer follow-up time beyond 1-5 years is needed, wrote Dr. Zheng and colleagues.

Studies also are needed to illustrate how patient navigation can help prevent patients from falling through the cracks with regard to social needs and financial hardships, Mr. Biru told this news organization.

Other areas for research include how addressing social needs affects health outcomes and whether programs designed to address social needs are effective, he said.

“Finally, qualitative research is needed to capture the lived experiences of cancer survivors facing these challenges. This knowledge can inform the development of more patient-centered interventions and policies that effectively address the social determinants of health and improve overall outcomes for all cancer survivors,” Mr. Biru said.
 

What Is the Takeaway Message for Clinicians?

HRSNs and financial hardship are significantly associated with increased risk of mortality in adult cancer survivors, Dr. Zheng and colleagues concluded. Looking ahead, comprehensive assessment of HRSNs and financial hardship may help clinicians connect patients with relevant services to mitigate the social and financial impacts of cancer, they wrote.

“The takeaway message for oncologists in practice is that addressing [HRSNs] and financial hardship is crucial for providing comprehensive and equitable cancer care,” Mr. Biru said during his interview.

“The impact of social determinants of health on cancer outcomes cannot be ignored, and oncologists play a vital role in identifying and addressing these needs,” he said. Sensitive, discussion-based screenings are needed to identify core needs such as food and transportation, but clinicians also can consider broader social factors and work with a team to connect patients to appropriate resources, he added.

“By recognizing the importance of HRSN screening and taking proactive steps to address these needs, oncologists can contribute to improving health outcomes, reducing healthcare disparities, and providing more equitable cancer care for their patients,” he said.
 

What Other Guidance Is Available?

“High-quality cancer care requires treating the whole person; measuring and addressing anything in their life that could result in poorer health outcomes is a key component of comprehensive care,” Mr. Biru emphasized.

In September 2023, the National Comprehensive Cancer Network (NCCN) convened a working group cochaired by Mr. Biru that developed recommendations for how oncology practices should routinely measure HRSNs (NCCN.org/social-needs).

“The working group proposed that every cancer patient be assessed for food, transportation access, and financial and housing security at least once a year, and be reassessed at every care transition point as well,” Mr. Biru said. Such screenings should include follow-up to connect patients with services to address any HRSNs they are experiencing, he added.

Lead author Dr. Zheng is employed by the American Cancer Society, which as a nonprofit receives funds from the public through fundraising and contributions, as well as some support from corporations and industry to support its mission programs and services. Mr. Biru had no financial conflicts to disclose.

Health-related social needs and medical financial hardship are associated with increased risk of mortality in adult cancer survivors, based on data from more than 10,000 individuals.

Little is known about the specific association between health-related social needs (HRSNs) and mortality risk even though HRSNs, defined as challenges in affording food, housing, and other necessities of daily living, are potential challenges for cancer survivors, wrote Zhiyuan Zheng, PhD, of the American Cancer Society, Atlanta, and colleagues.

A 2020 study by Dr. Zheng and colleagues published in the Journal of the National Comprehensive Cancer Network (NCCN) showed that food insecurity and financial worries had a negative impact on cancer survivorship. In the new study, published in Cancer, the researchers identified cancer survivors using the 2013-2018 National Health Interview Survey (NHIS) and the NHIS Mortality File through December 31, 2019. The researchers examined mortality using the data from the Centers for Disease Control and Prevention’s National Death Index (NDI) through December 31, 2019, which links to the National Health Interview Survey Data used in the study.

Individuals’ HRSNs were categorized into three groups: severe, moderate, and minor/none. HRSNs included food insecurity and nonmedical financial concerns, such as housing costs (rent, mortgage). Medical financial hardship included material, psychological, and behavioral domains and was divided into three groups: 2-3 domains, 1 domain, or 0 domains.
 

What Are the Potential Financial Implications of this Research?

The high costs of cancer care often cause medical financial hardships for cancer survivors, and expenses also may cause psychological distress and nonmedical financial hardship as survivors try to make ends meet while facing medical bills, wrote Dr. Zheng and colleagues.

Policy makers are increasingly interested in adding HRSNs to insurance coverage; recent guidance from the Centers for Medicare & Medicaid Services (CMS) allows individual states to apply to provide nutrition and housing supports through state Medicaid programs, according to authors of a 2023 article published in JAMA Health Forum.

The new study adds to the understanding of how HRSNs impact people with cancer by examining the association with mortality risk, Yelak Biru, MSc, president and chief executive officer of the International Myeloma Foundation, said in an interview.

“This is a key area of study for addressing the disparities in treatments and outcomes that result in inequities,” said Mr. Biru, a patient advocate and multiple myeloma survivor who was not involved in the study.
 

What Does the New Study Show?

The new study characterized HRSNs in 5,855 adult cancer survivors aged 18-64 years and 5,918 aged 65-79 years. In the 18- to 64-year-old group, 25.5% reported moderate levels of HRSNs, and 18.3% reported severe HRSNs. In patients aged 65-79 years, 15.6% and 6.6% reported moderate HRSNs and severe HRSNs, respectively.

Severe HRSN was significantly associated with higher mortality risk in an adjusted analysis in patients aged 18-64 years (hazard ratio 2.00, P < .001).

Among adults aged 65-79 years, severe HRSN was not associated with higher mortality risk; however, in this older age group, those with 2-3 domains of medical financial hardship had significantly increased mortality risk compared with adults aged 65-79 years with zero domains of medical financial hardship (HR 1.58, P = .007).

Although the findings that HRSNs were associated with increased mortality risk, especially in the younger group, were not surprising, they serve as a call to action to address how HRSNs are contributing to cancer mortality, Mr. Biru said in an interview. “HRSNs, like food or housing insecurity, can lead to patients being unable to undergo the best treatment approach for their cancer,” he said.
 

What Are the Limitations and Research Gaps?

The study findings were limited by several factors including the use of self-reports to measure medical financial hardship, food insecurity, and nonmedical financial concerns in the NHIS, the researchers wrote in their discussion. More research with longer follow-up time beyond 1-5 years is needed, wrote Dr. Zheng and colleagues.

Studies also are needed to illustrate how patient navigation can help prevent patients from falling through the cracks with regard to social needs and financial hardships, Mr. Biru told this news organization.

Other areas for research include how addressing social needs affects health outcomes and whether programs designed to address social needs are effective, he said.

“Finally, qualitative research is needed to capture the lived experiences of cancer survivors facing these challenges. This knowledge can inform the development of more patient-centered interventions and policies that effectively address the social determinants of health and improve overall outcomes for all cancer survivors,” Mr. Biru said.
 

What Is the Takeaway Message for Clinicians?

HRSNs and financial hardship are significantly associated with increased risk of mortality in adult cancer survivors, Dr. Zheng and colleagues concluded. Looking ahead, comprehensive assessment of HRSNs and financial hardship may help clinicians connect patients with relevant services to mitigate the social and financial impacts of cancer, they wrote.

“The takeaway message for oncologists in practice is that addressing [HRSNs] and financial hardship is crucial for providing comprehensive and equitable cancer care,” Mr. Biru said during his interview.

“The impact of social determinants of health on cancer outcomes cannot be ignored, and oncologists play a vital role in identifying and addressing these needs,” he said. Sensitive, discussion-based screenings are needed to identify core needs such as food and transportation, but clinicians also can consider broader social factors and work with a team to connect patients to appropriate resources, he added.

“By recognizing the importance of HRSN screening and taking proactive steps to address these needs, oncologists can contribute to improving health outcomes, reducing healthcare disparities, and providing more equitable cancer care for their patients,” he said.
 

What Other Guidance Is Available?

“High-quality cancer care requires treating the whole person; measuring and addressing anything in their life that could result in poorer health outcomes is a key component of comprehensive care,” Mr. Biru emphasized.

In September 2023, the National Comprehensive Cancer Network (NCCN) convened a working group cochaired by Mr. Biru that developed recommendations for how oncology practices should routinely measure HRSNs (NCCN.org/social-needs).

“The working group proposed that every cancer patient be assessed for food, transportation access, and financial and housing security at least once a year, and be reassessed at every care transition point as well,” Mr. Biru said. Such screenings should include follow-up to connect patients with services to address any HRSNs they are experiencing, he added.

Lead author Dr. Zheng is employed by the American Cancer Society, which as a nonprofit receives funds from the public through fundraising and contributions, as well as some support from corporations and industry to support its mission programs and services. Mr. Biru had no financial conflicts to disclose.

What’s most important to patients with terminal cancer and their caregivers?

New research found that patients and caregivers both tend to prioritize symptom control over life extension but often preferring a balance. Patients and caregivers, however, are less aligned on decisions about cost containment, with patients more likely to prioritize cost containment.

“Our research has revealed that patients and caregivers generally share similar end-of-life goals,” with a “notable exception” when it comes to costs, first author Semra Ozdemir, PhD, with the Lien Centre for Palliative Care, Duke-NUS Medical School, Singapore, told this news organization.

However, when patients and caregivers have a better understanding of the patient’s prognosis, both may be more inclined to avoid costly life-extending treatments and prioritize symptom management.

In other words, the survey suggests that “knowing the prognosis helps patients and their families set realistic expectations for care and adequately prepare for end-of-life decisions,” said Dr. Ozdemir.

This study was published online in JAMA Network Open.

Patients with advanced cancer often face difficult decisions: Do they opt for treatments that may — or may not — extend life or do they focus more on symptom control?

Family caregivers, who also play an important role in this decision-making process, may have different care goals. Some research suggests that caregivers tend to prioritize treatments that could extend life, whereas patients prioritize symptom management, but it’s less clear how these priorities may change over time and how patients and caregivers may influence each other.

In the current study, the researchers examined goals of care among patients with stage IV solid tumors and caregivers during the last 2 years of life, focusing on life extension vs symptom management and cost containment, as well as how these goals changed over time.

The survey included 210 patient-caregiver pairs, recruited from outpatient clinics at two major cancer centers in Singapore. Patients had a mean age of 63 years, and about half were men. The caregivers had a mean age of 49 years, and almost two third (63%) were women.

Overall, 34% patients and 29% caregivers prioritized symptom management over life extension, whereas 24% patients and 19% caregivers prioritized life extension. Most patients and caregivers preferred balancing the two, with 34%-47% patients and 37%-69% caregivers supporting this approach.

When balancing cost and treatment decisions, however, patients were more likely to prioritize containing costs — 28% vs 17% for caregivers — over extending life — 26% of patients vs 35% of caregivers.

Cost containment tended to be more of a priority for older patients, those with a higher symptom burden, and those with less family caregiver support. For caregivers, cost containment was more of a priority for those who reported that caregiving had a big impact on their finances, those with worse self-esteem related to their caregiving abilities, as well as those caring for older patients.

To better align cost containment priorities between patients and caregivers, it’s essential for families to engage in open and thorough discussions about the allocation of resources, Dr. Ozdemir said.

Although “patients, families, and physicians often avoid discussions about prognosis,” such conversations are essential for setting realistic expectations for care and adequately preparing for end-of-life decisions, Dr. Ozdemir told this news organization.

“These conversations should aim to balance competing interests and create care plans that are mutually acceptable to both patients and caregivers,” she said, adding that “this approach will help in minimizing any potential conflicts and ensure that both parties feel respected and understood in their decision-making process.”

Managing Unrealistic Expectations

As patients approached the end of life, neither patients nor caregivers shifted their priorities from life extension to symptom management.

This finding raises concerns because it suggests that many patients hold unrealistic expectations regarding their care and “underscores the need for continuous dialogue and reassessment of care goals throughout the progression of illness,” Dr. Ozdemir said.

“This stability in preferences over time suggests that initial care decisions are deeply ingrained or that there may be a lack of ongoing communication about evolving care needs and possibilities as conditions change,” Ozdemir said.

Yet, it can be hard to define what unrealistic expectations mean, said Olivia Seecof, MD, who wasn’t involved in the study.

“I think people are hopeful that a devastating diagnosis won’t lead to the end of their life and that there will be a treatment or something that will change [their prognosis], and they’ll get better,” said Dr. Seecof, palliative care expert with the Supportive Oncology Program at NYU Langone Health’s Perlmutter Cancer Center in New York City.

Giving patients and caregivers a realistic understanding of the prognosis is important, but “there’s more to it than just telling the patient their diagnosis,” she said.

“We have to plan for end of life, what it can look like,” said Dr. Seecof, adding that “often we don’t do a very good job of talking about that early on in an illness course.”

Overall, though, Dr. Seecof stressed that no two patients or situations are the same, and it’s important to understand what’s important in each scenario. End-of-life care requires “an individual approach because every patient is different, even if they have the same diagnosis as someone else,” she said.

This work was supported by funding from the Singapore Millennium Foundation and the Lien Centre for Palliative Care. Dr. Ozdemir and Dr. Seecof had no relevant disclosures.

A version of this article appeared on Medscape.com.

What’s most important to patients with terminal cancer and their caregivers?

New research found that patients and caregivers both tend to prioritize symptom control over life extension but often preferring a balance. Patients and caregivers, however, are less aligned on decisions about cost containment, with patients more likely to prioritize cost containment.

“Our research has revealed that patients and caregivers generally share similar end-of-life goals,” with a “notable exception” when it comes to costs, first author Semra Ozdemir, PhD, with the Lien Centre for Palliative Care, Duke-NUS Medical School, Singapore, told this news organization.

However, when patients and caregivers have a better understanding of the patient’s prognosis, both may be more inclined to avoid costly life-extending treatments and prioritize symptom management.

In other words, the survey suggests that “knowing the prognosis helps patients and their families set realistic expectations for care and adequately prepare for end-of-life decisions,” said Dr. Ozdemir.

This study was published online in JAMA Network Open.

Patients with advanced cancer often face difficult decisions: Do they opt for treatments that may — or may not — extend life or do they focus more on symptom control?

Family caregivers, who also play an important role in this decision-making process, may have different care goals. Some research suggests that caregivers tend to prioritize treatments that could extend life, whereas patients prioritize symptom management, but it’s less clear how these priorities may change over time and how patients and caregivers may influence each other.

In the current study, the researchers examined goals of care among patients with stage IV solid tumors and caregivers during the last 2 years of life, focusing on life extension vs symptom management and cost containment, as well as how these goals changed over time.

The survey included 210 patient-caregiver pairs, recruited from outpatient clinics at two major cancer centers in Singapore. Patients had a mean age of 63 years, and about half were men. The caregivers had a mean age of 49 years, and almost two third (63%) were women.

Overall, 34% patients and 29% caregivers prioritized symptom management over life extension, whereas 24% patients and 19% caregivers prioritized life extension. Most patients and caregivers preferred balancing the two, with 34%-47% patients and 37%-69% caregivers supporting this approach.

When balancing cost and treatment decisions, however, patients were more likely to prioritize containing costs — 28% vs 17% for caregivers — over extending life — 26% of patients vs 35% of caregivers.

Cost containment tended to be more of a priority for older patients, those with a higher symptom burden, and those with less family caregiver support. For caregivers, cost containment was more of a priority for those who reported that caregiving had a big impact on their finances, those with worse self-esteem related to their caregiving abilities, as well as those caring for older patients.

To better align cost containment priorities between patients and caregivers, it’s essential for families to engage in open and thorough discussions about the allocation of resources, Dr. Ozdemir said.

Although “patients, families, and physicians often avoid discussions about prognosis,” such conversations are essential for setting realistic expectations for care and adequately preparing for end-of-life decisions, Dr. Ozdemir told this news organization.

“These conversations should aim to balance competing interests and create care plans that are mutually acceptable to both patients and caregivers,” she said, adding that “this approach will help in minimizing any potential conflicts and ensure that both parties feel respected and understood in their decision-making process.”

Managing Unrealistic Expectations

As patients approached the end of life, neither patients nor caregivers shifted their priorities from life extension to symptom management.

This finding raises concerns because it suggests that many patients hold unrealistic expectations regarding their care and “underscores the need for continuous dialogue and reassessment of care goals throughout the progression of illness,” Dr. Ozdemir said.

“This stability in preferences over time suggests that initial care decisions are deeply ingrained or that there may be a lack of ongoing communication about evolving care needs and possibilities as conditions change,” Ozdemir said.

Yet, it can be hard to define what unrealistic expectations mean, said Olivia Seecof, MD, who wasn’t involved in the study.

“I think people are hopeful that a devastating diagnosis won’t lead to the end of their life and that there will be a treatment or something that will change [their prognosis], and they’ll get better,” said Dr. Seecof, palliative care expert with the Supportive Oncology Program at NYU Langone Health’s Perlmutter Cancer Center in New York City.

Giving patients and caregivers a realistic understanding of the prognosis is important, but “there’s more to it than just telling the patient their diagnosis,” she said.

“We have to plan for end of life, what it can look like,” said Dr. Seecof, adding that “often we don’t do a very good job of talking about that early on in an illness course.”

Overall, though, Dr. Seecof stressed that no two patients or situations are the same, and it’s important to understand what’s important in each scenario. End-of-life care requires “an individual approach because every patient is different, even if they have the same diagnosis as someone else,” she said.

This work was supported by funding from the Singapore Millennium Foundation and the Lien Centre for Palliative Care. Dr. Ozdemir and Dr. Seecof had no relevant disclosures.

A version of this article appeared on Medscape.com.

What’s most important to patients with terminal cancer and their caregivers?

New research found that patients and caregivers both tend to prioritize symptom control over life extension but often preferring a balance. Patients and caregivers, however, are less aligned on decisions about cost containment, with patients more likely to prioritize cost containment.

“Our research has revealed that patients and caregivers generally share similar end-of-life goals,” with a “notable exception” when it comes to costs, first author Semra Ozdemir, PhD, with the Lien Centre for Palliative Care, Duke-NUS Medical School, Singapore, told this news organization.

However, when patients and caregivers have a better understanding of the patient’s prognosis, both may be more inclined to avoid costly life-extending treatments and prioritize symptom management.

In other words, the survey suggests that “knowing the prognosis helps patients and their families set realistic expectations for care and adequately prepare for end-of-life decisions,” said Dr. Ozdemir.

This study was published online in JAMA Network Open.

Patients with advanced cancer often face difficult decisions: Do they opt for treatments that may — or may not — extend life or do they focus more on symptom control?

Family caregivers, who also play an important role in this decision-making process, may have different care goals. Some research suggests that caregivers tend to prioritize treatments that could extend life, whereas patients prioritize symptom management, but it’s less clear how these priorities may change over time and how patients and caregivers may influence each other.

In the current study, the researchers examined goals of care among patients with stage IV solid tumors and caregivers during the last 2 years of life, focusing on life extension vs symptom management and cost containment, as well as how these goals changed over time.

The survey included 210 patient-caregiver pairs, recruited from outpatient clinics at two major cancer centers in Singapore. Patients had a mean age of 63 years, and about half were men. The caregivers had a mean age of 49 years, and almost two third (63%) were women.

Overall, 34% patients and 29% caregivers prioritized symptom management over life extension, whereas 24% patients and 19% caregivers prioritized life extension. Most patients and caregivers preferred balancing the two, with 34%-47% patients and 37%-69% caregivers supporting this approach.

When balancing cost and treatment decisions, however, patients were more likely to prioritize containing costs — 28% vs 17% for caregivers — over extending life — 26% of patients vs 35% of caregivers.

Cost containment tended to be more of a priority for older patients, those with a higher symptom burden, and those with less family caregiver support. For caregivers, cost containment was more of a priority for those who reported that caregiving had a big impact on their finances, those with worse self-esteem related to their caregiving abilities, as well as those caring for older patients.

To better align cost containment priorities between patients and caregivers, it’s essential for families to engage in open and thorough discussions about the allocation of resources, Dr. Ozdemir said.

Although “patients, families, and physicians often avoid discussions about prognosis,” such conversations are essential for setting realistic expectations for care and adequately preparing for end-of-life decisions, Dr. Ozdemir told this news organization.

“These conversations should aim to balance competing interests and create care plans that are mutually acceptable to both patients and caregivers,” she said, adding that “this approach will help in minimizing any potential conflicts and ensure that both parties feel respected and understood in their decision-making process.”

Managing Unrealistic Expectations

As patients approached the end of life, neither patients nor caregivers shifted their priorities from life extension to symptom management.

This finding raises concerns because it suggests that many patients hold unrealistic expectations regarding their care and “underscores the need for continuous dialogue and reassessment of care goals throughout the progression of illness,” Dr. Ozdemir said.

“This stability in preferences over time suggests that initial care decisions are deeply ingrained or that there may be a lack of ongoing communication about evolving care needs and possibilities as conditions change,” Ozdemir said.

Yet, it can be hard to define what unrealistic expectations mean, said Olivia Seecof, MD, who wasn’t involved in the study.

“I think people are hopeful that a devastating diagnosis won’t lead to the end of their life and that there will be a treatment or something that will change [their prognosis], and they’ll get better,” said Dr. Seecof, palliative care expert with the Supportive Oncology Program at NYU Langone Health’s Perlmutter Cancer Center in New York City.

Giving patients and caregivers a realistic understanding of the prognosis is important, but “there’s more to it than just telling the patient their diagnosis,” she said.

“We have to plan for end of life, what it can look like,” said Dr. Seecof, adding that “often we don’t do a very good job of talking about that early on in an illness course.”

Overall, though, Dr. Seecof stressed that no two patients or situations are the same, and it’s important to understand what’s important in each scenario. End-of-life care requires “an individual approach because every patient is different, even if they have the same diagnosis as someone else,” she said.

This work was supported by funding from the Singapore Millennium Foundation and the Lien Centre for Palliative Care. Dr. Ozdemir and Dr. Seecof had no relevant disclosures.

A version of this article appeared on Medscape.com.

From India to Brazil, researchers around the world are experimenting with ways to simplify the complex production of chimeric antigen receptor (CAR) T cells and lower the treatment’s sky-high costs.

In the United States, a stand-alone device could greatly reduce the expense of producing modified immune cells. In India, researchers hope homegrown technology is the key to getting costs under control. In Latin America, a partnership between the Brazilian government and a US nonprofit may be just the ticket.

At stake is expanded access to CAR T-cell therapy, a form of immunotherapy that in just the past few years has revolutionized the care of hematologic cancers.

“Among patients with lymphoma, leukemia, and myeloma, anywhere between 30% to 50% reach long-term remission after one CAR T-cell infusion,” Mayo Clinic–Rochester hematologist/oncologist Saad J. Kenderian, MB, ChB, said in an interview. “It’s such an important therapy.”

However, only a small percentage of eligible patients in the United States — perhaps 20% or fewer — are receiving the treatment, he added.

A 2024 report suggested that many patients in the United States who may benefit aren’t being treated because of a range of possible reasons, including high prices, manufacturing logistics, and far distance from the limited number of institutions offering the therapy.

“Taken together, the real-world cost of CAR T-cell therapy can range from $700,000 to $1 million, which may make the treatment unaffordable to those patients without robust financial and/or social support,” the report authors noted.

Outside Western countries, access to the therapy is even more limited, because of its exorbitant price. The 2024 report noted that “there is a wide use of CAR T-cell therapy in Europe and China, but access is limited in developing countries in Southeast Asia, Africa, and Latin America.”
 

Harnessing the Power of T-Cells

Several types of CAR T-cell therapy have been approved by the US Food and Drug Administration (FDA) for patients with relapsed/refractory blood cancers such as follicular lymphoma, large B-cell lymphoma, multiple myeloma, and B-cell precursor acute lymphoblastic leukemia. A 2023 review analyzed clinical trials and reported that complete response rates were 40%-54% in aggressive B-cell lymphoma, 67% in mantle cell lymphoma, and 69%-74% in indolent B-cell lymphoma.

Pediatric hematologist/oncologist Kirsten Williams, MD, who specializes in pediatric blood and marrow transplant and cellular therapy at the Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta, described CAR T-cell therapy as “a very unique form of immunotherapy” that harnesses the power of the immune system’s T-cells.

These cells are effective tumor killers, but they typically aren’t assigned to control cancer, she said in an interview. “We have very few of them, and most of our T cells are focused on killing various viruses,” she said. The therapy “allows us to take the T cell that would have killed the flu or mono and instead target leukemia, B-cell leukemia, or lymphoma.”

As she explained, “T cells are collected by a machine that reserves white blood cells and gives back the rest of the blood to the patient. We insert a gene into the T cells that encodes for a B-cell receptor. This receptor acts as a GPS signal, pulling T cells to the cancer so that they can kill it.”

In addition, “with this genetic change, we also add some things that allow the T cell to be stronger, to have a higher signal to kill the cancer cell once it locks on.”

The therapy is unique for each patient, Dr. Williams said. “We have collected and modified your specific T cells, and they can now only be infused into you. If we try to give your product to someone else, those cells would either cause harm by attacking the patient or would be immediately killed by that patient’s own immune system. This is very different than all the other kinds of therapies. When you take other medicines, it doesn’t matter who receives that pill.”
 

Treatment: Individual, Complex, and Costly

Why is CAR T-cell therapy so expensive? While only a single treatment is needed, the T cells have to go through an “individualized, bespoke manufacturing” process that’s “highly technical,” pediatric oncologist Stephan A. Grupp, MD, PhD, section chief of the Cellular Therapy and Transplant Section at Children’s Hospital of Philadelphia, said in an interview. As he explained, the cells for a single patient have to go through the same testing as with a drug that might be given to 1,000 people.

“The first thing we need to do is collect the cells from a patient,” said Dr. Williams. “For adults, that process involves putting in two big IVs — one in each arm — and then pulling the blood through a machine. This typically involves an 8-hour collection in the hospital and very highly specialized people to oversee the collection process.”

Secondly, at some institutions, “the cells get sent to a company where they undergo the process where the gene is inserted,” she said. “This process needs to be done in a very sterile environment so there’s no infections, and it needs to have a lot of oversight.”

Finally, “after the cells are generated, they are typically frozen and shipped back to the site where the patient is at the hospital,” she said. “Then we give chemotherapy to the patient, which prepares the patient’s blood system. It removes some of the T-cells that are there, allowing for the T cells that we’re about to infuse to quickly be activated, find the cancer, and kill it.”

Side effects can boost costs even more. “Unfortunately, some significant toxicities can occur after we infuse these cells,” Dr. Williams noted. “Patients can have trouble breathing and sometimes need ventilatory support. They can have trouble maintaining their blood pressure and become swollen as fluid seeps into tissues. Or they can have high fevers and organ dysfunction. Many of those patients go to the intensive care unit, which is obviously expensive as well.”
 

Taking Gene Therapy In-House

As Dr. Williams explained, one way to reduce costs is to “perform the genetic manipulation and expansion of the cells outside of a company.” Several academic institutions in the United States are embracing this approach, including Children’s Hospital of Philadelphia, which is experimenting with an automated device developed by the German company Miltenyi Biotec and known as the CliniMACS Prodigy machine.

“The current manufacturing process is very manual and requires a lot of interaction with the product and highly trained personnel,” Dr. Grupp said. “If you have an automated device, you have those cells in the device over the 7 to 12 days that you actually need to grow the cells. There’s much less interaction, so you need fewer trained personnel.”

Children&#039;s Hospital of Philadelphia

India: Big Hopes for Homegrown Technology

In India, researchers are hoping that their homegrown approach to CAR T-cell therapy will expand access by greatly lowering treatment prices.

Last fall, India’s equivalent of the FDA-granted approval for actalycabtagene autoleucel (NexCAR19), which was developed by Indian scientists who worked closely with the US National Institutes of Health (NIH). The therapy’s developer is a company called ImmunoACT.

In an interview, ImmunoACT founder Rahul Purwar, PhD, MSc, associate professor at Indian Institute of Technology Bombay, said the treatment costs about $40,000. The price is much lower than in the United States because staffing, facility construction, and maintenance are less expensive in India, he said.

Results of small early clinical trials have been promising, with complete responses in 68% of 38 lymphoma patients and 72% of 15 leukemia patients. Updated data will be presented at the annual American Society of Hematology meeting in December 2024, Dr. Purwar said.

According to the NIH, at first ImmunoACT hopes to treat about 1,200 patients a year. The immediate goal is to “focus and stabilize our operation in India,” Dr. Purwar said. “Then, if opportunities come, we will try to bring CAR T to all who might benefit from these technologies. A majority of countries don’t have access to these technologies.”
 

A US-Brazil Partnership Holds Promise

Meanwhile, a US nonprofit known as Caring Cross announced this year that it has partnered with Fundação Oswaldo Cruz (Fiocruz), a Brazilian government foundation, to manufacture CAR T cells at point-of-care in South America.

“Our model is different than traditional biotech/pharma,” Boro Dropulic, PhD, MBA, cofounder and executive director of Caring Cross, said in an interview. “Our goal is to develop technologies and transfer them to organizations like Fiocruz to enable them to manufacture these transformative therapies for patients in their regions. We believe this model is an important solution for therapies that are priced so high that they are not accessible to many patients that need them, particularly underserved populations and those in low- and middle-income countries.”

According to Dr. Dropulic: “We have developed a production process where the material cost is about $20,000 per dose.” When labor and infrastructure costs are added, the total expense won’t be more than $37,000-$47,500, he said.

The research process for the CAR T-cell technology is at an earlier stage than in India. Scientists plan to start clinical trials of the technology in the United States by the end of 2024 and then begin them in Brazil in 2025, after safety and efficacy have been demonstrated. The first trial, a phase I/II study, will enroll about 20 patients, Dr. Dropulic said.

Dr. Kenderian reported ties with Novartis, Capstan Bio, Kite/Gilead, Juno/BMS, Humanigen, Tolero, Leah Labs, Lentigen, Luminary, Sunesis/Viracta, Morphosys, Troque, Carisma, Sendero, and LifEngine. Dr. Williams disclosed grants from National Institutes of Health and philanthropic organizations. Dr. Grupp reported relationships with Novartis, Kite, Vertex and Servier, Roche, GSK, Humanigen, CBMG, Eureka, Janssen/JNJ, Jazz, Adaptimmune, TCR2, Cellectis, Juno, Allogene, and Cabaletta. Dr. Purwar is the founder of ImmunoACT. Dr. Dropulic serves as executive director of Caring Cross and CEO of Vector BioMed, which provides vectors for gene therapy.

From India to Brazil, researchers around the world are experimenting with ways to simplify the complex production of chimeric antigen receptor (CAR) T cells and lower the treatment’s sky-high costs.

In the United States, a stand-alone device could greatly reduce the expense of producing modified immune cells. In India, researchers hope homegrown technology is the key to getting costs under control. In Latin America, a partnership between the Brazilian government and a US nonprofit may be just the ticket.

At stake is expanded access to CAR T-cell therapy, a form of immunotherapy that in just the past few years has revolutionized the care of hematologic cancers.

“Among patients with lymphoma, leukemia, and myeloma, anywhere between 30% to 50% reach long-term remission after one CAR T-cell infusion,” Mayo Clinic–Rochester hematologist/oncologist Saad J. Kenderian, MB, ChB, said in an interview. “It’s such an important therapy.”

However, only a small percentage of eligible patients in the United States — perhaps 20% or fewer — are receiving the treatment, he added.

A 2024 report suggested that many patients in the United States who may benefit aren’t being treated because of a range of possible reasons, including high prices, manufacturing logistics, and far distance from the limited number of institutions offering the therapy.

“Taken together, the real-world cost of CAR T-cell therapy can range from $700,000 to $1 million, which may make the treatment unaffordable to those patients without robust financial and/or social support,” the report authors noted.

Outside Western countries, access to the therapy is even more limited, because of its exorbitant price. The 2024 report noted that “there is a wide use of CAR T-cell therapy in Europe and China, but access is limited in developing countries in Southeast Asia, Africa, and Latin America.”
 

Harnessing the Power of T-Cells

Several types of CAR T-cell therapy have been approved by the US Food and Drug Administration (FDA) for patients with relapsed/refractory blood cancers such as follicular lymphoma, large B-cell lymphoma, multiple myeloma, and B-cell precursor acute lymphoblastic leukemia. A 2023 review analyzed clinical trials and reported that complete response rates were 40%-54% in aggressive B-cell lymphoma, 67% in mantle cell lymphoma, and 69%-74% in indolent B-cell lymphoma.

Pediatric hematologist/oncologist Kirsten Williams, MD, who specializes in pediatric blood and marrow transplant and cellular therapy at the Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta, described CAR T-cell therapy as “a very unique form of immunotherapy” that harnesses the power of the immune system’s T-cells.

These cells are effective tumor killers, but they typically aren’t assigned to control cancer, she said in an interview. “We have very few of them, and most of our T cells are focused on killing various viruses,” she said. The therapy “allows us to take the T cell that would have killed the flu or mono and instead target leukemia, B-cell leukemia, or lymphoma.”

As she explained, “T cells are collected by a machine that reserves white blood cells and gives back the rest of the blood to the patient. We insert a gene into the T cells that encodes for a B-cell receptor. This receptor acts as a GPS signal, pulling T cells to the cancer so that they can kill it.”

In addition, “with this genetic change, we also add some things that allow the T cell to be stronger, to have a higher signal to kill the cancer cell once it locks on.”

The therapy is unique for each patient, Dr. Williams said. “We have collected and modified your specific T cells, and they can now only be infused into you. If we try to give your product to someone else, those cells would either cause harm by attacking the patient or would be immediately killed by that patient’s own immune system. This is very different than all the other kinds of therapies. When you take other medicines, it doesn’t matter who receives that pill.”
 

Treatment: Individual, Complex, and Costly

Why is CAR T-cell therapy so expensive? While only a single treatment is needed, the T cells have to go through an “individualized, bespoke manufacturing” process that’s “highly technical,” pediatric oncologist Stephan A. Grupp, MD, PhD, section chief of the Cellular Therapy and Transplant Section at Children’s Hospital of Philadelphia, said in an interview. As he explained, the cells for a single patient have to go through the same testing as with a drug that might be given to 1,000 people.

“The first thing we need to do is collect the cells from a patient,” said Dr. Williams. “For adults, that process involves putting in two big IVs — one in each arm — and then pulling the blood through a machine. This typically involves an 8-hour collection in the hospital and very highly specialized people to oversee the collection process.”

Secondly, at some institutions, “the cells get sent to a company where they undergo the process where the gene is inserted,” she said. “This process needs to be done in a very sterile environment so there’s no infections, and it needs to have a lot of oversight.”

Finally, “after the cells are generated, they are typically frozen and shipped back to the site where the patient is at the hospital,” she said. “Then we give chemotherapy to the patient, which prepares the patient’s blood system. It removes some of the T-cells that are there, allowing for the T cells that we’re about to infuse to quickly be activated, find the cancer, and kill it.”

Side effects can boost costs even more. “Unfortunately, some significant toxicities can occur after we infuse these cells,” Dr. Williams noted. “Patients can have trouble breathing and sometimes need ventilatory support. They can have trouble maintaining their blood pressure and become swollen as fluid seeps into tissues. Or they can have high fevers and organ dysfunction. Many of those patients go to the intensive care unit, which is obviously expensive as well.”
 

Taking Gene Therapy In-House

As Dr. Williams explained, one way to reduce costs is to “perform the genetic manipulation and expansion of the cells outside of a company.” Several academic institutions in the United States are embracing this approach, including Children’s Hospital of Philadelphia, which is experimenting with an automated device developed by the German company Miltenyi Biotec and known as the CliniMACS Prodigy machine.

“The current manufacturing process is very manual and requires a lot of interaction with the product and highly trained personnel,” Dr. Grupp said. “If you have an automated device, you have those cells in the device over the 7 to 12 days that you actually need to grow the cells. There’s much less interaction, so you need fewer trained personnel.”

Children&#039;s Hospital of Philadelphia

India: Big Hopes for Homegrown Technology

In India, researchers are hoping that their homegrown approach to CAR T-cell therapy will expand access by greatly lowering treatment prices.

Last fall, India’s equivalent of the FDA-granted approval for actalycabtagene autoleucel (NexCAR19), which was developed by Indian scientists who worked closely with the US National Institutes of Health (NIH). The therapy’s developer is a company called ImmunoACT.

In an interview, ImmunoACT founder Rahul Purwar, PhD, MSc, associate professor at Indian Institute of Technology Bombay, said the treatment costs about $40,000. The price is much lower than in the United States because staffing, facility construction, and maintenance are less expensive in India, he said.

Results of small early clinical trials have been promising, with complete responses in 68% of 38 lymphoma patients and 72% of 15 leukemia patients. Updated data will be presented at the annual American Society of Hematology meeting in December 2024, Dr. Purwar said.

According to the NIH, at first ImmunoACT hopes to treat about 1,200 patients a year. The immediate goal is to “focus and stabilize our operation in India,” Dr. Purwar said. “Then, if opportunities come, we will try to bring CAR T to all who might benefit from these technologies. A majority of countries don’t have access to these technologies.”
 

A US-Brazil Partnership Holds Promise

Meanwhile, a US nonprofit known as Caring Cross announced this year that it has partnered with Fundação Oswaldo Cruz (Fiocruz), a Brazilian government foundation, to manufacture CAR T cells at point-of-care in South America.

“Our model is different than traditional biotech/pharma,” Boro Dropulic, PhD, MBA, cofounder and executive director of Caring Cross, said in an interview. “Our goal is to develop technologies and transfer them to organizations like Fiocruz to enable them to manufacture these transformative therapies for patients in their regions. We believe this model is an important solution for therapies that are priced so high that they are not accessible to many patients that need them, particularly underserved populations and those in low- and middle-income countries.”

According to Dr. Dropulic: “We have developed a production process where the material cost is about $20,000 per dose.” When labor and infrastructure costs are added, the total expense won’t be more than $37,000-$47,500, he said.

The research process for the CAR T-cell technology is at an earlier stage than in India. Scientists plan to start clinical trials of the technology in the United States by the end of 2024 and then begin them in Brazil in 2025, after safety and efficacy have been demonstrated. The first trial, a phase I/II study, will enroll about 20 patients, Dr. Dropulic said.

Dr. Kenderian reported ties with Novartis, Capstan Bio, Kite/Gilead, Juno/BMS, Humanigen, Tolero, Leah Labs, Lentigen, Luminary, Sunesis/Viracta, Morphosys, Troque, Carisma, Sendero, and LifEngine. Dr. Williams disclosed grants from National Institutes of Health and philanthropic organizations. Dr. Grupp reported relationships with Novartis, Kite, Vertex and Servier, Roche, GSK, Humanigen, CBMG, Eureka, Janssen/JNJ, Jazz, Adaptimmune, TCR2, Cellectis, Juno, Allogene, and Cabaletta. Dr. Purwar is the founder of ImmunoACT. Dr. Dropulic serves as executive director of Caring Cross and CEO of Vector BioMed, which provides vectors for gene therapy.

From India to Brazil, researchers around the world are experimenting with ways to simplify the complex production of chimeric antigen receptor (CAR) T cells and lower the treatment’s sky-high costs.

In the United States, a stand-alone device could greatly reduce the expense of producing modified immune cells. In India, researchers hope homegrown technology is the key to getting costs under control. In Latin America, a partnership between the Brazilian government and a US nonprofit may be just the ticket.

At stake is expanded access to CAR T-cell therapy, a form of immunotherapy that in just the past few years has revolutionized the care of hematologic cancers.

“Among patients with lymphoma, leukemia, and myeloma, anywhere between 30% to 50% reach long-term remission after one CAR T-cell infusion,” Mayo Clinic–Rochester hematologist/oncologist Saad J. Kenderian, MB, ChB, said in an interview. “It’s such an important therapy.”

However, only a small percentage of eligible patients in the United States — perhaps 20% or fewer — are receiving the treatment, he added.

A 2024 report suggested that many patients in the United States who may benefit aren’t being treated because of a range of possible reasons, including high prices, manufacturing logistics, and far distance from the limited number of institutions offering the therapy.

“Taken together, the real-world cost of CAR T-cell therapy can range from $700,000 to $1 million, which may make the treatment unaffordable to those patients without robust financial and/or social support,” the report authors noted.

Outside Western countries, access to the therapy is even more limited, because of its exorbitant price. The 2024 report noted that “there is a wide use of CAR T-cell therapy in Europe and China, but access is limited in developing countries in Southeast Asia, Africa, and Latin America.”
 

Harnessing the Power of T-Cells

Several types of CAR T-cell therapy have been approved by the US Food and Drug Administration (FDA) for patients with relapsed/refractory blood cancers such as follicular lymphoma, large B-cell lymphoma, multiple myeloma, and B-cell precursor acute lymphoblastic leukemia. A 2023 review analyzed clinical trials and reported that complete response rates were 40%-54% in aggressive B-cell lymphoma, 67% in mantle cell lymphoma, and 69%-74% in indolent B-cell lymphoma.

Pediatric hematologist/oncologist Kirsten Williams, MD, who specializes in pediatric blood and marrow transplant and cellular therapy at the Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta, described CAR T-cell therapy as “a very unique form of immunotherapy” that harnesses the power of the immune system’s T-cells.

These cells are effective tumor killers, but they typically aren’t assigned to control cancer, she said in an interview. “We have very few of them, and most of our T cells are focused on killing various viruses,” she said. The therapy “allows us to take the T cell that would have killed the flu or mono and instead target leukemia, B-cell leukemia, or lymphoma.”

As she explained, “T cells are collected by a machine that reserves white blood cells and gives back the rest of the blood to the patient. We insert a gene into the T cells that encodes for a B-cell receptor. This receptor acts as a GPS signal, pulling T cells to the cancer so that they can kill it.”

In addition, “with this genetic change, we also add some things that allow the T cell to be stronger, to have a higher signal to kill the cancer cell once it locks on.”

The therapy is unique for each patient, Dr. Williams said. “We have collected and modified your specific T cells, and they can now only be infused into you. If we try to give your product to someone else, those cells would either cause harm by attacking the patient or would be immediately killed by that patient’s own immune system. This is very different than all the other kinds of therapies. When you take other medicines, it doesn’t matter who receives that pill.”
 

Treatment: Individual, Complex, and Costly

Why is CAR T-cell therapy so expensive? While only a single treatment is needed, the T cells have to go through an “individualized, bespoke manufacturing” process that’s “highly technical,” pediatric oncologist Stephan A. Grupp, MD, PhD, section chief of the Cellular Therapy and Transplant Section at Children’s Hospital of Philadelphia, said in an interview. As he explained, the cells for a single patient have to go through the same testing as with a drug that might be given to 1,000 people.

“The first thing we need to do is collect the cells from a patient,” said Dr. Williams. “For adults, that process involves putting in two big IVs — one in each arm — and then pulling the blood through a machine. This typically involves an 8-hour collection in the hospital and very highly specialized people to oversee the collection process.”

Secondly, at some institutions, “the cells get sent to a company where they undergo the process where the gene is inserted,” she said. “This process needs to be done in a very sterile environment so there’s no infections, and it needs to have a lot of oversight.”

Finally, “after the cells are generated, they are typically frozen and shipped back to the site where the patient is at the hospital,” she said. “Then we give chemotherapy to the patient, which prepares the patient’s blood system. It removes some of the T-cells that are there, allowing for the T cells that we’re about to infuse to quickly be activated, find the cancer, and kill it.”

Side effects can boost costs even more. “Unfortunately, some significant toxicities can occur after we infuse these cells,” Dr. Williams noted. “Patients can have trouble breathing and sometimes need ventilatory support. They can have trouble maintaining their blood pressure and become swollen as fluid seeps into tissues. Or they can have high fevers and organ dysfunction. Many of those patients go to the intensive care unit, which is obviously expensive as well.”
 

Taking Gene Therapy In-House

As Dr. Williams explained, one way to reduce costs is to “perform the genetic manipulation and expansion of the cells outside of a company.” Several academic institutions in the United States are embracing this approach, including Children’s Hospital of Philadelphia, which is experimenting with an automated device developed by the German company Miltenyi Biotec and known as the CliniMACS Prodigy machine.

“The current manufacturing process is very manual and requires a lot of interaction with the product and highly trained personnel,” Dr. Grupp said. “If you have an automated device, you have those cells in the device over the 7 to 12 days that you actually need to grow the cells. There’s much less interaction, so you need fewer trained personnel.”

Children&#039;s Hospital of Philadelphia

India: Big Hopes for Homegrown Technology

In India, researchers are hoping that their homegrown approach to CAR T-cell therapy will expand access by greatly lowering treatment prices.

Last fall, India’s equivalent of the FDA-granted approval for actalycabtagene autoleucel (NexCAR19), which was developed by Indian scientists who worked closely with the US National Institutes of Health (NIH). The therapy’s developer is a company called ImmunoACT.

In an interview, ImmunoACT founder Rahul Purwar, PhD, MSc, associate professor at Indian Institute of Technology Bombay, said the treatment costs about $40,000. The price is much lower than in the United States because staffing, facility construction, and maintenance are less expensive in India, he said.

Results of small early clinical trials have been promising, with complete responses in 68% of 38 lymphoma patients and 72% of 15 leukemia patients. Updated data will be presented at the annual American Society of Hematology meeting in December 2024, Dr. Purwar said.

According to the NIH, at first ImmunoACT hopes to treat about 1,200 patients a year. The immediate goal is to “focus and stabilize our operation in India,” Dr. Purwar said. “Then, if opportunities come, we will try to bring CAR T to all who might benefit from these technologies. A majority of countries don’t have access to these technologies.”
 

A US-Brazil Partnership Holds Promise

Meanwhile, a US nonprofit known as Caring Cross announced this year that it has partnered with Fundação Oswaldo Cruz (Fiocruz), a Brazilian government foundation, to manufacture CAR T cells at point-of-care in South America.

“Our model is different than traditional biotech/pharma,” Boro Dropulic, PhD, MBA, cofounder and executive director of Caring Cross, said in an interview. “Our goal is to develop technologies and transfer them to organizations like Fiocruz to enable them to manufacture these transformative therapies for patients in their regions. We believe this model is an important solution for therapies that are priced so high that they are not accessible to many patients that need them, particularly underserved populations and those in low- and middle-income countries.”

According to Dr. Dropulic: “We have developed a production process where the material cost is about $20,000 per dose.” When labor and infrastructure costs are added, the total expense won’t be more than $37,000-$47,500, he said.

The research process for the CAR T-cell technology is at an earlier stage than in India. Scientists plan to start clinical trials of the technology in the United States by the end of 2024 and then begin them in Brazil in 2025, after safety and efficacy have been demonstrated. The first trial, a phase I/II study, will enroll about 20 patients, Dr. Dropulic said.

Dr. Kenderian reported ties with Novartis, Capstan Bio, Kite/Gilead, Juno/BMS, Humanigen, Tolero, Leah Labs, Lentigen, Luminary, Sunesis/Viracta, Morphosys, Troque, Carisma, Sendero, and LifEngine. Dr. Williams disclosed grants from National Institutes of Health and philanthropic organizations. Dr. Grupp reported relationships with Novartis, Kite, Vertex and Servier, Roche, GSK, Humanigen, CBMG, Eureka, Janssen/JNJ, Jazz, Adaptimmune, TCR2, Cellectis, Juno, Allogene, and Cabaletta. Dr. Purwar is the founder of ImmunoACT. Dr. Dropulic serves as executive director of Caring Cross and CEO of Vector BioMed, which provides vectors for gene therapy.

In addition to warmer weather, June will usher in changes in asthma and COPD inhaler costs for many patients, potentially reducing barriers to those seeing high prescription prices. Price ceilings have been set by some companies, likely following action earlier this year by a Senate Committee which pointed to higher costs of US inhalers compared with other countries.

Senator Sanders stated: “In my view, Americans who have asthma and COPD should not be forced to pay, in many cases, 10-70 times more for the same exact inhalers as patients in Europe and other parts of the world.”

Starting June 1, Boehringer Ingelheim will cap out-of-pocket costs for the company’s inhaler products for chronic lung disease and asthma at $35 per month, according to a March 7, 2024, press release from the German drugmaker’s US headquarters in Ridgefield, Conn. The reductions cover the full range of the company’s inhaler products for asthma and chronic obstructive pulmonary disease (COPD) including Atrovent, Combivent Respimat and Spiriva HandiHaler and Respimat, Stiolto Respimat and Striverdi Respimat. In the release, Boehringer Ingelheim USA Corporation’s President and CEO Jean-Michel Boers stated, “The US health care system is complex and often doesn’t work for patients, especially the most vulnerable. While we can’t fix the entire system alone, we are bringing forward a solution to make it fairer. We want to do our part to help patients living with COPD or asthma who struggle to pay for their medications.”

Similar announcements were made by AstraZeneca and GSK. GSK’s cap will go into effect on January 1, 2025, and includes Advair Diskus, Advair HFA, Anoro Ellipta, Arnuity Ellipta, Breo Ellipta, Incruse Ellipta, Serevent Diskus, Trelegy Ellipta, and Ventolin HFA. The AstraZeneca cap, which covers Airsupra, Bevespi Aerosphere, Breztri Aeroshpere, and Symbicort, goes into effect on June 1, 2024.
 

Senate statement on pricing

These companies plus Teva had received letters sent on January 8, 2024, by the members of the Senate Committee on Health, Education, Labor, and Pensions: senators Sanders, Baldwin, Luján and Markey. The letters cited enormous inhaler price discrepancies, for example $489 for Combivent Respimat in the United States but just $7 in France, and announced the conduct of an investigation into efforts by these companies to artificially inflate and manipulate prices of asthma inhalers that have been on the market for decades. A statement from Sen. Sanders’ office noted that AstraZeneca, GSK, and Teva made more than $25 billion in revenue from inhalers alone in the past 5 years (Boehringer Ingelheim does not provide public US inhaler revenue information).

Suit claims generic delay

A federal lawsuit filed in Boston on March 6, according to a Reuters brief from March 7, cited Boehringer for improperly submitting patents to the US Food and Drug Administration (FDA). The purpose of those patents, the suit charges, was to delay generic competition and inflate Combivent Respimat and Spiriva Respimat inhaler prices.

Inhaler prices soared in the United States, according to a March 10 U.S. News & World Report commentary by The Conversation, a nonprofit news organization, after the 2008 FDA ban on chlorofluorocarbon (CFC)-propellants led to the phase-out of CFC-containing inhalers and their replacement with hydrofluoroalkane-propellant inhalers. For the insured that meant an average out-of-pocket inhaler cost increase from $13.60 per prescription in 2004 to $25 in 2015. The current rate for the now nongeneric HFA-propelled but otherwise identical albuterol inhaler is $98. Competition from a more recently FDA-approved (2020) generic version has not been robust enough to effect meaningful price reductions, the report stated. While good insurance generally covers most of inhaler costs, the more than 25 million uninsured in 2023 faced steep market prices that put strain even on some insured, the CDC found, driving many in the United States to purchase from Mexican, Canadian, or other foreign pharmacies. The Teva QVAR REdiHaler corticosteroid inhaler, costing $9 in Germany, costs $286 in the US. Dosages, however, may not be identical. A first FDA-authorization of drug importing this past January applied only to agents for a limited number of disease states and pertained only to Florida, but may serve as a model for other states, according to the commentary.

“The announced price cap from Boehringer Ingelheim,” stated Kenneth Mendez, president and CEO of the Asthma and Allergy Foundation of America (AAFA) in a press release, “is a step toward improving access to essential asthma medicine and demonstrates that the voice of the asthma patient community is being heard.” The AAFA release noted further that asthma death rates, while declining overall, are triple in Blacks compared with Whites. Death rates, asthma rates, and rates of being uninsured or underinsured are much higher in Black and Puerto Rican populations than in Whites. The complex layers of the current US system, composed of pharmaceutical manufacturers, pharmacy benefit managers, insurance companies, employers, and federal policies often conspire against those people who need asthma drugs the most. AAFA research has shown that when drug prices become a barrier to treatment, people with asthma ration or simply discontinue their essential asthma medications. Beyond saved lives, access to asthma medications can reduce hospitalizations and lower the more than $82 billion in annual asthma costs to the US economy.

Sen. Sanders, on March 20, applauded the GSK announcement: “As Chairman of the Senate Health, Education, Labor, and Pensions Committee, I very much appreciate GlaxoSmithKline’s announcement today that Americans throughout the country with asthma and COPD will pay no more than $35 for the brand name inhalers they manufacture. I look forward to working with GSK to make sure that this decision reaches as many patients as possible.”

“Inhaled medications continue to be an essential part of the therapy for patients with asthma, COPD, and other respiratory conditions,” said Diego J. Maselli, professor and chief, Division of Pulmonary Diseases & Critical Care, UT Health at San Antonio, San Antonio, Texas, in an interview with CHEST Physician. He added, “Unfortunately, with increasing cost of these and other treatments, access has been challenging for many patients. Patients, families, and providers constantly experience frustration with the difficulties of obtaining these lifesaving medications, and cost is the main barrier. Even those with ample insurance coverage face difficult challenges, as the high prices of these medications motivate insurance carriers to constantly adjust what is the ‘preferred’ option among inhalers. Regrettably, noncompliance and nonadherence to inhaled therapies has been linked to poor patient outcomes and increased health care utilization in both asthma and COPD. Because of the high prevalence of these diseases in the US and worldwide, efforts to increase the access of these vital medications has been a priority. With the leveling of the prices of these medications across the world, we hope that there will be both improved access and, as a consequence, better patient outcomes.”

In addition to warmer weather, June will usher in changes in asthma and COPD inhaler costs for many patients, potentially reducing barriers to those seeing high prescription prices. Price ceilings have been set by some companies, likely following action earlier this year by a Senate Committee which pointed to higher costs of US inhalers compared with other countries.

Senator Sanders stated: “In my view, Americans who have asthma and COPD should not be forced to pay, in many cases, 10-70 times more for the same exact inhalers as patients in Europe and other parts of the world.”

Starting June 1, Boehringer Ingelheim will cap out-of-pocket costs for the company’s inhaler products for chronic lung disease and asthma at $35 per month, according to a March 7, 2024, press release from the German drugmaker’s US headquarters in Ridgefield, Conn. The reductions cover the full range of the company’s inhaler products for asthma and chronic obstructive pulmonary disease (COPD) including Atrovent, Combivent Respimat and Spiriva HandiHaler and Respimat, Stiolto Respimat and Striverdi Respimat. In the release, Boehringer Ingelheim USA Corporation’s President and CEO Jean-Michel Boers stated, “The US health care system is complex and often doesn’t work for patients, especially the most vulnerable. While we can’t fix the entire system alone, we are bringing forward a solution to make it fairer. We want to do our part to help patients living with COPD or asthma who struggle to pay for their medications.”

Similar announcements were made by AstraZeneca and GSK. GSK’s cap will go into effect on January 1, 2025, and includes Advair Diskus, Advair HFA, Anoro Ellipta, Arnuity Ellipta, Breo Ellipta, Incruse Ellipta, Serevent Diskus, Trelegy Ellipta, and Ventolin HFA. The AstraZeneca cap, which covers Airsupra, Bevespi Aerosphere, Breztri Aeroshpere, and Symbicort, goes into effect on June 1, 2024.
 

Senate statement on pricing

These companies plus Teva had received letters sent on January 8, 2024, by the members of the Senate Committee on Health, Education, Labor, and Pensions: senators Sanders, Baldwin, Luján and Markey. The letters cited enormous inhaler price discrepancies, for example $489 for Combivent Respimat in the United States but just $7 in France, and announced the conduct of an investigation into efforts by these companies to artificially inflate and manipulate prices of asthma inhalers that have been on the market for decades. A statement from Sen. Sanders’ office noted that AstraZeneca, GSK, and Teva made more than $25 billion in revenue from inhalers alone in the past 5 years (Boehringer Ingelheim does not provide public US inhaler revenue information).

Suit claims generic delay

A federal lawsuit filed in Boston on March 6, according to a Reuters brief from March 7, cited Boehringer for improperly submitting patents to the US Food and Drug Administration (FDA). The purpose of those patents, the suit charges, was to delay generic competition and inflate Combivent Respimat and Spiriva Respimat inhaler prices.

Inhaler prices soared in the United States, according to a March 10 U.S. News & World Report commentary by The Conversation, a nonprofit news organization, after the 2008 FDA ban on chlorofluorocarbon (CFC)-propellants led to the phase-out of CFC-containing inhalers and their replacement with hydrofluoroalkane-propellant inhalers. For the insured that meant an average out-of-pocket inhaler cost increase from $13.60 per prescription in 2004 to $25 in 2015. The current rate for the now nongeneric HFA-propelled but otherwise identical albuterol inhaler is $98. Competition from a more recently FDA-approved (2020) generic version has not been robust enough to effect meaningful price reductions, the report stated. While good insurance generally covers most of inhaler costs, the more than 25 million uninsured in 2023 faced steep market prices that put strain even on some insured, the CDC found, driving many in the United States to purchase from Mexican, Canadian, or other foreign pharmacies. The Teva QVAR REdiHaler corticosteroid inhaler, costing $9 in Germany, costs $286 in the US. Dosages, however, may not be identical. A first FDA-authorization of drug importing this past January applied only to agents for a limited number of disease states and pertained only to Florida, but may serve as a model for other states, according to the commentary.

“The announced price cap from Boehringer Ingelheim,” stated Kenneth Mendez, president and CEO of the Asthma and Allergy Foundation of America (AAFA) in a press release, “is a step toward improving access to essential asthma medicine and demonstrates that the voice of the asthma patient community is being heard.” The AAFA release noted further that asthma death rates, while declining overall, are triple in Blacks compared with Whites. Death rates, asthma rates, and rates of being uninsured or underinsured are much higher in Black and Puerto Rican populations than in Whites. The complex layers of the current US system, composed of pharmaceutical manufacturers, pharmacy benefit managers, insurance companies, employers, and federal policies often conspire against those people who need asthma drugs the most. AAFA research has shown that when drug prices become a barrier to treatment, people with asthma ration or simply discontinue their essential asthma medications. Beyond saved lives, access to asthma medications can reduce hospitalizations and lower the more than $82 billion in annual asthma costs to the US economy.

Sen. Sanders, on March 20, applauded the GSK announcement: “As Chairman of the Senate Health, Education, Labor, and Pensions Committee, I very much appreciate GlaxoSmithKline’s announcement today that Americans throughout the country with asthma and COPD will pay no more than $35 for the brand name inhalers they manufacture. I look forward to working with GSK to make sure that this decision reaches as many patients as possible.”

“Inhaled medications continue to be an essential part of the therapy for patients with asthma, COPD, and other respiratory conditions,” said Diego J. Maselli, professor and chief, Division of Pulmonary Diseases & Critical Care, UT Health at San Antonio, San Antonio, Texas, in an interview with CHEST Physician. He added, “Unfortunately, with increasing cost of these and other treatments, access has been challenging for many patients. Patients, families, and providers constantly experience frustration with the difficulties of obtaining these lifesaving medications, and cost is the main barrier. Even those with ample insurance coverage face difficult challenges, as the high prices of these medications motivate insurance carriers to constantly adjust what is the ‘preferred’ option among inhalers. Regrettably, noncompliance and nonadherence to inhaled therapies has been linked to poor patient outcomes and increased health care utilization in both asthma and COPD. Because of the high prevalence of these diseases in the US and worldwide, efforts to increase the access of these vital medications has been a priority. With the leveling of the prices of these medications across the world, we hope that there will be both improved access and, as a consequence, better patient outcomes.”

In addition to warmer weather, June will usher in changes in asthma and COPD inhaler costs for many patients, potentially reducing barriers to those seeing high prescription prices. Price ceilings have been set by some companies, likely following action earlier this year by a Senate Committee which pointed to higher costs of US inhalers compared with other countries.

Senator Sanders stated: “In my view, Americans who have asthma and COPD should not be forced to pay, in many cases, 10-70 times more for the same exact inhalers as patients in Europe and other parts of the world.”

Starting June 1, Boehringer Ingelheim will cap out-of-pocket costs for the company’s inhaler products for chronic lung disease and asthma at $35 per month, according to a March 7, 2024, press release from the German drugmaker’s US headquarters in Ridgefield, Conn. The reductions cover the full range of the company’s inhaler products for asthma and chronic obstructive pulmonary disease (COPD) including Atrovent, Combivent Respimat and Spiriva HandiHaler and Respimat, Stiolto Respimat and Striverdi Respimat. In the release, Boehringer Ingelheim USA Corporation’s President and CEO Jean-Michel Boers stated, “The US health care system is complex and often doesn’t work for patients, especially the most vulnerable. While we can’t fix the entire system alone, we are bringing forward a solution to make it fairer. We want to do our part to help patients living with COPD or asthma who struggle to pay for their medications.”

Similar announcements were made by AstraZeneca and GSK. GSK’s cap will go into effect on January 1, 2025, and includes Advair Diskus, Advair HFA, Anoro Ellipta, Arnuity Ellipta, Breo Ellipta, Incruse Ellipta, Serevent Diskus, Trelegy Ellipta, and Ventolin HFA. The AstraZeneca cap, which covers Airsupra, Bevespi Aerosphere, Breztri Aeroshpere, and Symbicort, goes into effect on June 1, 2024.
 

Senate statement on pricing

These companies plus Teva had received letters sent on January 8, 2024, by the members of the Senate Committee on Health, Education, Labor, and Pensions: senators Sanders, Baldwin, Luján and Markey. The letters cited enormous inhaler price discrepancies, for example $489 for Combivent Respimat in the United States but just $7 in France, and announced the conduct of an investigation into efforts by these companies to artificially inflate and manipulate prices of asthma inhalers that have been on the market for decades. A statement from Sen. Sanders’ office noted that AstraZeneca, GSK, and Teva made more than $25 billion in revenue from inhalers alone in the past 5 years (Boehringer Ingelheim does not provide public US inhaler revenue information).

Suit claims generic delay

A federal lawsuit filed in Boston on March 6, according to a Reuters brief from March 7, cited Boehringer for improperly submitting patents to the US Food and Drug Administration (FDA). The purpose of those patents, the suit charges, was to delay generic competition and inflate Combivent Respimat and Spiriva Respimat inhaler prices.

Inhaler prices soared in the United States, according to a March 10 U.S. News & World Report commentary by The Conversation, a nonprofit news organization, after the 2008 FDA ban on chlorofluorocarbon (CFC)-propellants led to the phase-out of CFC-containing inhalers and their replacement with hydrofluoroalkane-propellant inhalers. For the insured that meant an average out-of-pocket inhaler cost increase from $13.60 per prescription in 2004 to $25 in 2015. The current rate for the now nongeneric HFA-propelled but otherwise identical albuterol inhaler is $98. Competition from a more recently FDA-approved (2020) generic version has not been robust enough to effect meaningful price reductions, the report stated. While good insurance generally covers most of inhaler costs, the more than 25 million uninsured in 2023 faced steep market prices that put strain even on some insured, the CDC found, driving many in the United States to purchase from Mexican, Canadian, or other foreign pharmacies. The Teva QVAR REdiHaler corticosteroid inhaler, costing $9 in Germany, costs $286 in the US. Dosages, however, may not be identical. A first FDA-authorization of drug importing this past January applied only to agents for a limited number of disease states and pertained only to Florida, but may serve as a model for other states, according to the commentary.

“The announced price cap from Boehringer Ingelheim,” stated Kenneth Mendez, president and CEO of the Asthma and Allergy Foundation of America (AAFA) in a press release, “is a step toward improving access to essential asthma medicine and demonstrates that the voice of the asthma patient community is being heard.” The AAFA release noted further that asthma death rates, while declining overall, are triple in Blacks compared with Whites. Death rates, asthma rates, and rates of being uninsured or underinsured are much higher in Black and Puerto Rican populations than in Whites. The complex layers of the current US system, composed of pharmaceutical manufacturers, pharmacy benefit managers, insurance companies, employers, and federal policies often conspire against those people who need asthma drugs the most. AAFA research has shown that when drug prices become a barrier to treatment, people with asthma ration or simply discontinue their essential asthma medications. Beyond saved lives, access to asthma medications can reduce hospitalizations and lower the more than $82 billion in annual asthma costs to the US economy.

Sen. Sanders, on March 20, applauded the GSK announcement: “As Chairman of the Senate Health, Education, Labor, and Pensions Committee, I very much appreciate GlaxoSmithKline’s announcement today that Americans throughout the country with asthma and COPD will pay no more than $35 for the brand name inhalers they manufacture. I look forward to working with GSK to make sure that this decision reaches as many patients as possible.”

“Inhaled medications continue to be an essential part of the therapy for patients with asthma, COPD, and other respiratory conditions,” said Diego J. Maselli, professor and chief, Division of Pulmonary Diseases & Critical Care, UT Health at San Antonio, San Antonio, Texas, in an interview with CHEST Physician. He added, “Unfortunately, with increasing cost of these and other treatments, access has been challenging for many patients. Patients, families, and providers constantly experience frustration with the difficulties of obtaining these lifesaving medications, and cost is the main barrier. Even those with ample insurance coverage face difficult challenges, as the high prices of these medications motivate insurance carriers to constantly adjust what is the ‘preferred’ option among inhalers. Regrettably, noncompliance and nonadherence to inhaled therapies has been linked to poor patient outcomes and increased health care utilization in both asthma and COPD. Because of the high prevalence of these diseases in the US and worldwide, efforts to increase the access of these vital medications has been a priority. With the leveling of the prices of these medications across the world, we hope that there will be both improved access and, as a consequence, better patient outcomes.”