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Physicians Call Out Barriers in Addiction Care
Physicians who fail to help patients suffering from addiction blame their institutions and their own limitations in skill, knowledge, available brainpower, and faith that interventions will help patients, a systematic review found.
Researchers analyzed 283 international studies with data from 66,732 physicians who were asked about their reluctance to address addiction treatment and substance use. , reported Wilson M. Compton, MD, deputy director of the National Institute on Drug Abuse, Baltimore, and colleagues, in JAMA Network Open.
Lack of Priority in Addiction Care
In an interview, Sarah Wakeman, MD, senior medical director for substance use disorder at Mass General Brigham, Boston, questioned the lack of priority given to addiction care. “Many of the perceived barriers that physicians cite for why they don’t offer addiction treatment exist for many types of health conditions we routinely manage,” said Dr. Wakeman, who’s familiar with the findings but didn’t take part in the study. “Yet we as physicians would never opt out of treating diabetes or heart disease. So why is it acceptable to opt out of treating addiction?”
As the review notes, an estimate suggests that more than 46 million people in the United States were diagnosed with substance abuse disorder in the past year, and misuse of alcohol and illegal drugs costs more than $442 billion a year. However, few people with addiction get treatment — estimated at only 6.3% in 2021 — and screening rates are low.
According to its authors, the review’s goal is to summarize studies into barriers to evidence-based addiction strategies such as screening, referral to treatment, medications, and behavioral interventions.
The researchers analyzed 283 studies from 1960 to 2021, mainly (64.0%) from 2010 to 2021, with only a few (2.7%) from before 2000. Most (60.1%) were survey-based, and most (59.4%) were from the United States. The studies mainly examined alcohol, opioid, and tobacco addiction.
Challenges in Treating Addiction
The studies pinpointed various challenges in the treatment of people with addiction. On the institution front, they noted obstacles such as lack of trained staff, prior authorization hassles, lack of insurance coverage, and “acceptance of addiction interventions by staff,” according to the review. In terms of knowledge and skill, “knowledge was more deficient for treatment than for screening or diagnosis and for drug use more than for alcohol or tobacco use.”
Available brainpower “was not often characterized beyond a general sense of overwhelm with clinical tasks (eg, ‘just too busy’) and the need to prioritize patients’ competing needs,” the review stated.
The review authors wrote that “other reasons for reluctance (eg, negative social influences, negative emotions toward people who use drugs, and fear of harming the relationship with the patient by discussing substance use) could each be viewed as manifestations of stigma associated with substance use disorder and its treatment.”
The review identified limitations such as “inconsistent use of terms” across studies and lack of detail in some studies about participation by the “audience of focus.” Additionally, the authors noted that the medical treatments for addiction have evolved over the past several decades, as has the drug market.
Dr. Wakeman said the review is well done with unsurprising results. “It is helpful to understand what physicians perceive the barriers to be so that further interventions can be designed to surmount those barriers, such as skills training or educational interventions,” she said.
Going forward, she said, “we need to end substance use disorder exceptionalism and stop approaching addiction treatment as if it is something different from the rest of healthcare.”
In an interview, Michael L. Barnett, MD, associate professor of health policy and management at Harvard T.H. Chan School of Public Health, Boston, said the review is “very thorough and documents a really wide literature that is difficult to summarize, which is an impressive contribution.”
Dr. Barnett, who’s familiar with the review findings but didn’t take part in the research, also noted that the review doesn’t confirm whether the perceived obstacles actually exist or how they can be fixed. In addition, he said, “the authors spend very little time addressing the elephant in the room, which is that addiction care is poorly compensated. If physicians made 10 times the money for addiction care, I bet a lot of this ‘reluctance’ would disappear.”
Additionally, he said, “It’s easy to endorse innocuous excuses for reluctance when the real reason is that a physician just doesn’t want to treat a stigmatized population.”
The study was funded by the National Institute on Drug Abuse. Two authors disclosed receiving support from the Intramural Research Program, National Institute on Drug Abuse, and National Institutes of Health. Dr. Wakeman is an author and a textbook editor for Wolters Kluwer and Springer. Dr. Barnett had no disclosures.
A version of this article first appeared on Medscape.com.
Physicians who fail to help patients suffering from addiction blame their institutions and their own limitations in skill, knowledge, available brainpower, and faith that interventions will help patients, a systematic review found.
Researchers analyzed 283 international studies with data from 66,732 physicians who were asked about their reluctance to address addiction treatment and substance use. , reported Wilson M. Compton, MD, deputy director of the National Institute on Drug Abuse, Baltimore, and colleagues, in JAMA Network Open.
Lack of Priority in Addiction Care
In an interview, Sarah Wakeman, MD, senior medical director for substance use disorder at Mass General Brigham, Boston, questioned the lack of priority given to addiction care. “Many of the perceived barriers that physicians cite for why they don’t offer addiction treatment exist for many types of health conditions we routinely manage,” said Dr. Wakeman, who’s familiar with the findings but didn’t take part in the study. “Yet we as physicians would never opt out of treating diabetes or heart disease. So why is it acceptable to opt out of treating addiction?”
As the review notes, an estimate suggests that more than 46 million people in the United States were diagnosed with substance abuse disorder in the past year, and misuse of alcohol and illegal drugs costs more than $442 billion a year. However, few people with addiction get treatment — estimated at only 6.3% in 2021 — and screening rates are low.
According to its authors, the review’s goal is to summarize studies into barriers to evidence-based addiction strategies such as screening, referral to treatment, medications, and behavioral interventions.
The researchers analyzed 283 studies from 1960 to 2021, mainly (64.0%) from 2010 to 2021, with only a few (2.7%) from before 2000. Most (60.1%) were survey-based, and most (59.4%) were from the United States. The studies mainly examined alcohol, opioid, and tobacco addiction.
Challenges in Treating Addiction
The studies pinpointed various challenges in the treatment of people with addiction. On the institution front, they noted obstacles such as lack of trained staff, prior authorization hassles, lack of insurance coverage, and “acceptance of addiction interventions by staff,” according to the review. In terms of knowledge and skill, “knowledge was more deficient for treatment than for screening or diagnosis and for drug use more than for alcohol or tobacco use.”
Available brainpower “was not often characterized beyond a general sense of overwhelm with clinical tasks (eg, ‘just too busy’) and the need to prioritize patients’ competing needs,” the review stated.
The review authors wrote that “other reasons for reluctance (eg, negative social influences, negative emotions toward people who use drugs, and fear of harming the relationship with the patient by discussing substance use) could each be viewed as manifestations of stigma associated with substance use disorder and its treatment.”
The review identified limitations such as “inconsistent use of terms” across studies and lack of detail in some studies about participation by the “audience of focus.” Additionally, the authors noted that the medical treatments for addiction have evolved over the past several decades, as has the drug market.
Dr. Wakeman said the review is well done with unsurprising results. “It is helpful to understand what physicians perceive the barriers to be so that further interventions can be designed to surmount those barriers, such as skills training or educational interventions,” she said.
Going forward, she said, “we need to end substance use disorder exceptionalism and stop approaching addiction treatment as if it is something different from the rest of healthcare.”
In an interview, Michael L. Barnett, MD, associate professor of health policy and management at Harvard T.H. Chan School of Public Health, Boston, said the review is “very thorough and documents a really wide literature that is difficult to summarize, which is an impressive contribution.”
Dr. Barnett, who’s familiar with the review findings but didn’t take part in the research, also noted that the review doesn’t confirm whether the perceived obstacles actually exist or how they can be fixed. In addition, he said, “the authors spend very little time addressing the elephant in the room, which is that addiction care is poorly compensated. If physicians made 10 times the money for addiction care, I bet a lot of this ‘reluctance’ would disappear.”
Additionally, he said, “It’s easy to endorse innocuous excuses for reluctance when the real reason is that a physician just doesn’t want to treat a stigmatized population.”
The study was funded by the National Institute on Drug Abuse. Two authors disclosed receiving support from the Intramural Research Program, National Institute on Drug Abuse, and National Institutes of Health. Dr. Wakeman is an author and a textbook editor for Wolters Kluwer and Springer. Dr. Barnett had no disclosures.
A version of this article first appeared on Medscape.com.
Physicians who fail to help patients suffering from addiction blame their institutions and their own limitations in skill, knowledge, available brainpower, and faith that interventions will help patients, a systematic review found.
Researchers analyzed 283 international studies with data from 66,732 physicians who were asked about their reluctance to address addiction treatment and substance use. , reported Wilson M. Compton, MD, deputy director of the National Institute on Drug Abuse, Baltimore, and colleagues, in JAMA Network Open.
Lack of Priority in Addiction Care
In an interview, Sarah Wakeman, MD, senior medical director for substance use disorder at Mass General Brigham, Boston, questioned the lack of priority given to addiction care. “Many of the perceived barriers that physicians cite for why they don’t offer addiction treatment exist for many types of health conditions we routinely manage,” said Dr. Wakeman, who’s familiar with the findings but didn’t take part in the study. “Yet we as physicians would never opt out of treating diabetes or heart disease. So why is it acceptable to opt out of treating addiction?”
As the review notes, an estimate suggests that more than 46 million people in the United States were diagnosed with substance abuse disorder in the past year, and misuse of alcohol and illegal drugs costs more than $442 billion a year. However, few people with addiction get treatment — estimated at only 6.3% in 2021 — and screening rates are low.
According to its authors, the review’s goal is to summarize studies into barriers to evidence-based addiction strategies such as screening, referral to treatment, medications, and behavioral interventions.
The researchers analyzed 283 studies from 1960 to 2021, mainly (64.0%) from 2010 to 2021, with only a few (2.7%) from before 2000. Most (60.1%) were survey-based, and most (59.4%) were from the United States. The studies mainly examined alcohol, opioid, and tobacco addiction.
Challenges in Treating Addiction
The studies pinpointed various challenges in the treatment of people with addiction. On the institution front, they noted obstacles such as lack of trained staff, prior authorization hassles, lack of insurance coverage, and “acceptance of addiction interventions by staff,” according to the review. In terms of knowledge and skill, “knowledge was more deficient for treatment than for screening or diagnosis and for drug use more than for alcohol or tobacco use.”
Available brainpower “was not often characterized beyond a general sense of overwhelm with clinical tasks (eg, ‘just too busy’) and the need to prioritize patients’ competing needs,” the review stated.
The review authors wrote that “other reasons for reluctance (eg, negative social influences, negative emotions toward people who use drugs, and fear of harming the relationship with the patient by discussing substance use) could each be viewed as manifestations of stigma associated with substance use disorder and its treatment.”
The review identified limitations such as “inconsistent use of terms” across studies and lack of detail in some studies about participation by the “audience of focus.” Additionally, the authors noted that the medical treatments for addiction have evolved over the past several decades, as has the drug market.
Dr. Wakeman said the review is well done with unsurprising results. “It is helpful to understand what physicians perceive the barriers to be so that further interventions can be designed to surmount those barriers, such as skills training or educational interventions,” she said.
Going forward, she said, “we need to end substance use disorder exceptionalism and stop approaching addiction treatment as if it is something different from the rest of healthcare.”
In an interview, Michael L. Barnett, MD, associate professor of health policy and management at Harvard T.H. Chan School of Public Health, Boston, said the review is “very thorough and documents a really wide literature that is difficult to summarize, which is an impressive contribution.”
Dr. Barnett, who’s familiar with the review findings but didn’t take part in the research, also noted that the review doesn’t confirm whether the perceived obstacles actually exist or how they can be fixed. In addition, he said, “the authors spend very little time addressing the elephant in the room, which is that addiction care is poorly compensated. If physicians made 10 times the money for addiction care, I bet a lot of this ‘reluctance’ would disappear.”
Additionally, he said, “It’s easy to endorse innocuous excuses for reluctance when the real reason is that a physician just doesn’t want to treat a stigmatized population.”
The study was funded by the National Institute on Drug Abuse. Two authors disclosed receiving support from the Intramural Research Program, National Institute on Drug Abuse, and National Institutes of Health. Dr. Wakeman is an author and a textbook editor for Wolters Kluwer and Springer. Dr. Barnett had no disclosures.
A version of this article first appeared on Medscape.com.
ASCO 2024: An Expert’s Top Hematology Highlights
Research presented at the annual meeting of the American Society of Clinical Oncology (ASCO) has the potential to change practice — and assumptions — about acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and blood cancer as a whole, according to the chief science officer of the American Cancer Society.
In an interview following the conference, Arif H. Kamal, MD, MBA, MHS, who practices hematology-oncology at Duke University, Durham, North Carolina, recapped several landmark studies and discussed their lessons for clinicians.
Question: You’ve highlighted a randomized, multisite clinical trialled by a researcher from Massachusetts General Hospital in Boston. The researchers enrolled 115 adult patients with AML or high-risk myelodysplastic syndrome (MDS) who were receiving non–intensive care to usual care or regular meetings with palliative care clinicians (monthly as outpatients and at least twice weekly as inpatients). Among those who died (61.7%), those in the intervention group had their end-of-life preferences documented much earlier (41 days before death vs. 1.5 days, P < .001). They were also more likely to have documented end-of-life care preferences (96.5% vs. 68.4%, P < .001) and less likely to have been hospitalized within the last month of life (70.6% vs. 91.9%, P = .031). Why did this study strike you as especially important?
Dr. Kamal: A few studies have now shown better outcomes in hematology after the use of early palliative care. This has been shown not only in transplant patients but also in non-transplant patients with hematologic malignancies. As a result, you’re seeing a shift toward regular integration of palliative care.
The historical concern has been that palliative care takes the foot off the gas pedal. Another way to look at it is that palliative care helps keep the foot on the gas pedal.
Q: Should the focus be on all hematologic cancer patients or just on those who are more severe cases or whose illness is terminal?
Dr. Kamal: The focus is on patients with acute progressive leukemias rather than those with indolent, long-standing lymphomas. This a reflection of severity and complexity: In leukemia, you can be someone really sick all of a sudden and require intensive treatment.
Q: What’s new about this kind of research?
Dr. Kamal: We’re learning how palliative care is valuable in all cancers, but particularly in blood cancers, where it has historically not been studied. The groundbreaking studies in palliative care over the last 20 years have largely been in solid tumors such as lung cancers and colorectal cancers.
Q: What is unique about the patient experience in hematologic cancers compared to solid tumor cancers?
Dr. Kamal: Blood cancers are a relatively new place to integrate palliative care, but what we’re finding is that it may be even more needed than in solid tumors in terms of improving outcomes.
In pancreatic cancer, you may not know if something is going to work, but it is going to take you months to figure it out. In leukemia, there can be a lot of dynamism: You’re going to find out in a matter of days. You have to be able to pivot really quickly to the next thing, go to transplant very quickly and urgently, or make a decision to pursue supportive care.
This really compresses the normal issues like uncertainty and emotional anxiety that a pancreatic cancer patient may process over a year. Leukemic patients may need to process that over 2, 3, or 4 weeks. Palliative care can be there to help the patient to process options.
Q: You also highlighted the industry-funded phase 3 ASC4FIRST study into asciminib (Scemblix) in newly diagnosed patients with CML. The trial was led by a researcher from the South Australian Health and Medical Research Institute and the University of Adelaide, Australia. Asciminib, a STAMP inhibitor, is FDA-approved for certain CML indications. In an intention-to-treat analysis, the new study finds better major molecular response at 48 weeks for the drug vs. investigator-selected tyrosine kinase inhibitors (67.7% vs. 49.0%, P < .001). What do these findings tell you?
Dr. Kamal: CML has been a disease where you had Gleevec — imatinib — and additional options that were all in the second-line or third-line setting after failure. Now, you’re seeing durable responses across the board: an expansion of options and potentially new options in the first-line setting.
[Editor’s note: For more about asciminib, check commentaries from physicians who spoke to Medscape and ASCO Daily News.]
Q: What makes this drug unique?
Dr. Kamal: CML was the leader in helping us to understand that if you identify a mutation, you can create a medication against it. Now, what we’re finding out is that there are other ways to work around mutations. Asciminib is not affected by the most common mutations that lend to drug resistance in the classic drugs that target BCR-ABL cells like imatinib.
Q: Finally, you spotlighted a retrospective study led by researchers at Case Western Reserve University that explored rates of obesity-related cancers — including multiple myeloma — in patients with BMI ≥ 35 who took glucagon-like protein-1 receptor agonists (GLP-1 RAs) or underwent bariatric surgery. Both strategies were linked to lower risk of the cancers vs. no intervention (GLP-1 RAs, hazard ratio [HR] = 0.61; 95% CI 0.46-0.81, and bariatric surgery, HR = 0.78; 95% CI 0.67-0.91). What did you learn from this research?
Dr. Kamal: When we think about risk reduction for cancer, we generally think about hormone-driven cancers. Blood cancers are not typically hormone-driven.
This study is hinting at that idea that healthy weight across the board will reduce your cancer risk even in blood cancers, and pharmacologic interventions to reduce your weight may also reduce that cancer risk.
Q: So weight-loss drugs such as Ozempic could potentially lower the risk of hematologic cancer?
Dr. Kamal: We’re going to need more data on this, and you wouldn’t take it for that reason. But there may be a story here that says get to a healthy weight — it doesn’t matter how you do it — and your risk of all cancers goes down.
Dr. Kamal has no disclosures to report.
Research presented at the annual meeting of the American Society of Clinical Oncology (ASCO) has the potential to change practice — and assumptions — about acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and blood cancer as a whole, according to the chief science officer of the American Cancer Society.
In an interview following the conference, Arif H. Kamal, MD, MBA, MHS, who practices hematology-oncology at Duke University, Durham, North Carolina, recapped several landmark studies and discussed their lessons for clinicians.
Question: You’ve highlighted a randomized, multisite clinical trialled by a researcher from Massachusetts General Hospital in Boston. The researchers enrolled 115 adult patients with AML or high-risk myelodysplastic syndrome (MDS) who were receiving non–intensive care to usual care or regular meetings with palliative care clinicians (monthly as outpatients and at least twice weekly as inpatients). Among those who died (61.7%), those in the intervention group had their end-of-life preferences documented much earlier (41 days before death vs. 1.5 days, P < .001). They were also more likely to have documented end-of-life care preferences (96.5% vs. 68.4%, P < .001) and less likely to have been hospitalized within the last month of life (70.6% vs. 91.9%, P = .031). Why did this study strike you as especially important?
Dr. Kamal: A few studies have now shown better outcomes in hematology after the use of early palliative care. This has been shown not only in transplant patients but also in non-transplant patients with hematologic malignancies. As a result, you’re seeing a shift toward regular integration of palliative care.
The historical concern has been that palliative care takes the foot off the gas pedal. Another way to look at it is that palliative care helps keep the foot on the gas pedal.
Q: Should the focus be on all hematologic cancer patients or just on those who are more severe cases or whose illness is terminal?
Dr. Kamal: The focus is on patients with acute progressive leukemias rather than those with indolent, long-standing lymphomas. This a reflection of severity and complexity: In leukemia, you can be someone really sick all of a sudden and require intensive treatment.
Q: What’s new about this kind of research?
Dr. Kamal: We’re learning how palliative care is valuable in all cancers, but particularly in blood cancers, where it has historically not been studied. The groundbreaking studies in palliative care over the last 20 years have largely been in solid tumors such as lung cancers and colorectal cancers.
Q: What is unique about the patient experience in hematologic cancers compared to solid tumor cancers?
Dr. Kamal: Blood cancers are a relatively new place to integrate palliative care, but what we’re finding is that it may be even more needed than in solid tumors in terms of improving outcomes.
In pancreatic cancer, you may not know if something is going to work, but it is going to take you months to figure it out. In leukemia, there can be a lot of dynamism: You’re going to find out in a matter of days. You have to be able to pivot really quickly to the next thing, go to transplant very quickly and urgently, or make a decision to pursue supportive care.
This really compresses the normal issues like uncertainty and emotional anxiety that a pancreatic cancer patient may process over a year. Leukemic patients may need to process that over 2, 3, or 4 weeks. Palliative care can be there to help the patient to process options.
Q: You also highlighted the industry-funded phase 3 ASC4FIRST study into asciminib (Scemblix) in newly diagnosed patients with CML. The trial was led by a researcher from the South Australian Health and Medical Research Institute and the University of Adelaide, Australia. Asciminib, a STAMP inhibitor, is FDA-approved for certain CML indications. In an intention-to-treat analysis, the new study finds better major molecular response at 48 weeks for the drug vs. investigator-selected tyrosine kinase inhibitors (67.7% vs. 49.0%, P < .001). What do these findings tell you?
Dr. Kamal: CML has been a disease where you had Gleevec — imatinib — and additional options that were all in the second-line or third-line setting after failure. Now, you’re seeing durable responses across the board: an expansion of options and potentially new options in the first-line setting.
[Editor’s note: For more about asciminib, check commentaries from physicians who spoke to Medscape and ASCO Daily News.]
Q: What makes this drug unique?
Dr. Kamal: CML was the leader in helping us to understand that if you identify a mutation, you can create a medication against it. Now, what we’re finding out is that there are other ways to work around mutations. Asciminib is not affected by the most common mutations that lend to drug resistance in the classic drugs that target BCR-ABL cells like imatinib.
Q: Finally, you spotlighted a retrospective study led by researchers at Case Western Reserve University that explored rates of obesity-related cancers — including multiple myeloma — in patients with BMI ≥ 35 who took glucagon-like protein-1 receptor agonists (GLP-1 RAs) or underwent bariatric surgery. Both strategies were linked to lower risk of the cancers vs. no intervention (GLP-1 RAs, hazard ratio [HR] = 0.61; 95% CI 0.46-0.81, and bariatric surgery, HR = 0.78; 95% CI 0.67-0.91). What did you learn from this research?
Dr. Kamal: When we think about risk reduction for cancer, we generally think about hormone-driven cancers. Blood cancers are not typically hormone-driven.
This study is hinting at that idea that healthy weight across the board will reduce your cancer risk even in blood cancers, and pharmacologic interventions to reduce your weight may also reduce that cancer risk.
Q: So weight-loss drugs such as Ozempic could potentially lower the risk of hematologic cancer?
Dr. Kamal: We’re going to need more data on this, and you wouldn’t take it for that reason. But there may be a story here that says get to a healthy weight — it doesn’t matter how you do it — and your risk of all cancers goes down.
Dr. Kamal has no disclosures to report.
Research presented at the annual meeting of the American Society of Clinical Oncology (ASCO) has the potential to change practice — and assumptions — about acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and blood cancer as a whole, according to the chief science officer of the American Cancer Society.
In an interview following the conference, Arif H. Kamal, MD, MBA, MHS, who practices hematology-oncology at Duke University, Durham, North Carolina, recapped several landmark studies and discussed their lessons for clinicians.
Question: You’ve highlighted a randomized, multisite clinical trialled by a researcher from Massachusetts General Hospital in Boston. The researchers enrolled 115 adult patients with AML or high-risk myelodysplastic syndrome (MDS) who were receiving non–intensive care to usual care or regular meetings with palliative care clinicians (monthly as outpatients and at least twice weekly as inpatients). Among those who died (61.7%), those in the intervention group had their end-of-life preferences documented much earlier (41 days before death vs. 1.5 days, P < .001). They were also more likely to have documented end-of-life care preferences (96.5% vs. 68.4%, P < .001) and less likely to have been hospitalized within the last month of life (70.6% vs. 91.9%, P = .031). Why did this study strike you as especially important?
Dr. Kamal: A few studies have now shown better outcomes in hematology after the use of early palliative care. This has been shown not only in transplant patients but also in non-transplant patients with hematologic malignancies. As a result, you’re seeing a shift toward regular integration of palliative care.
The historical concern has been that palliative care takes the foot off the gas pedal. Another way to look at it is that palliative care helps keep the foot on the gas pedal.
Q: Should the focus be on all hematologic cancer patients or just on those who are more severe cases or whose illness is terminal?
Dr. Kamal: The focus is on patients with acute progressive leukemias rather than those with indolent, long-standing lymphomas. This a reflection of severity and complexity: In leukemia, you can be someone really sick all of a sudden and require intensive treatment.
Q: What’s new about this kind of research?
Dr. Kamal: We’re learning how palliative care is valuable in all cancers, but particularly in blood cancers, where it has historically not been studied. The groundbreaking studies in palliative care over the last 20 years have largely been in solid tumors such as lung cancers and colorectal cancers.
Q: What is unique about the patient experience in hematologic cancers compared to solid tumor cancers?
Dr. Kamal: Blood cancers are a relatively new place to integrate palliative care, but what we’re finding is that it may be even more needed than in solid tumors in terms of improving outcomes.
In pancreatic cancer, you may not know if something is going to work, but it is going to take you months to figure it out. In leukemia, there can be a lot of dynamism: You’re going to find out in a matter of days. You have to be able to pivot really quickly to the next thing, go to transplant very quickly and urgently, or make a decision to pursue supportive care.
This really compresses the normal issues like uncertainty and emotional anxiety that a pancreatic cancer patient may process over a year. Leukemic patients may need to process that over 2, 3, or 4 weeks. Palliative care can be there to help the patient to process options.
Q: You also highlighted the industry-funded phase 3 ASC4FIRST study into asciminib (Scemblix) in newly diagnosed patients with CML. The trial was led by a researcher from the South Australian Health and Medical Research Institute and the University of Adelaide, Australia. Asciminib, a STAMP inhibitor, is FDA-approved for certain CML indications. In an intention-to-treat analysis, the new study finds better major molecular response at 48 weeks for the drug vs. investigator-selected tyrosine kinase inhibitors (67.7% vs. 49.0%, P < .001). What do these findings tell you?
Dr. Kamal: CML has been a disease where you had Gleevec — imatinib — and additional options that were all in the second-line or third-line setting after failure. Now, you’re seeing durable responses across the board: an expansion of options and potentially new options in the first-line setting.
[Editor’s note: For more about asciminib, check commentaries from physicians who spoke to Medscape and ASCO Daily News.]
Q: What makes this drug unique?
Dr. Kamal: CML was the leader in helping us to understand that if you identify a mutation, you can create a medication against it. Now, what we’re finding out is that there are other ways to work around mutations. Asciminib is not affected by the most common mutations that lend to drug resistance in the classic drugs that target BCR-ABL cells like imatinib.
Q: Finally, you spotlighted a retrospective study led by researchers at Case Western Reserve University that explored rates of obesity-related cancers — including multiple myeloma — in patients with BMI ≥ 35 who took glucagon-like protein-1 receptor agonists (GLP-1 RAs) or underwent bariatric surgery. Both strategies were linked to lower risk of the cancers vs. no intervention (GLP-1 RAs, hazard ratio [HR] = 0.61; 95% CI 0.46-0.81, and bariatric surgery, HR = 0.78; 95% CI 0.67-0.91). What did you learn from this research?
Dr. Kamal: When we think about risk reduction for cancer, we generally think about hormone-driven cancers. Blood cancers are not typically hormone-driven.
This study is hinting at that idea that healthy weight across the board will reduce your cancer risk even in blood cancers, and pharmacologic interventions to reduce your weight may also reduce that cancer risk.
Q: So weight-loss drugs such as Ozempic could potentially lower the risk of hematologic cancer?
Dr. Kamal: We’re going to need more data on this, and you wouldn’t take it for that reason. But there may be a story here that says get to a healthy weight — it doesn’t matter how you do it — and your risk of all cancers goes down.
Dr. Kamal has no disclosures to report.
In Prostate Cancer, Most Roads Lead to VA Pathway
The newly updated US Department of Veterans Affairs (VA) prostate cancer clinical pathway looks like a set of guidelines, but it’s really something unique. As attendees learned at an Association of VA Hematology/Oncology (AVAHO) regional meeting in Detroit in June, the clinical pathways are designed to point the way toward a standard ideal treatment for the majority of cases, not just to suggest a number of possible options.
“Pathways will always offer one scenario. They try to get oncologists to practice in a similar fashion so things can be managed more uniformly,” Michael M. Goodman, MD, told Federal Practitioner prior to the AVAHO meeting that was focused on prostate cancer care. Goodman is an associate professor of medicine with Atrium Health Wake Forest Baptist Medical Center and helped develop the VA genitourinary oncology pathways.
“The overall goal is not just to standardize care as much as possible but also to synthesize the best and most cost-effective practices,” Goodman said. For example, “If you have 5 different therapies, and they all have about the same efficacy and safety, and 1 is less costly than the other 4, then it would make sense to choose that.”
The VA has offered pathways for multiple types of cancer since 2021, and the pathway for prostate cancer is among the most comprehensive. The VA system updated the pathway in March 2024, is available online both via SharePoint and externally.
“It goes through the entire gamut from screening, diagnosis, and management to end of life,” Goodman explained. Multiple disciplines, from primary care and surgery to genetics and imaging, can rely on the pathway to assist decision-making.
In terms of screening, the pathway offers a flow map guiding the screening choices. In patients aged ≤ 54 years, only certain high-risk groups, such as African Americans and those with a family history of prostate cancer, should be screened. From ages 54 to 69 years, patients should be consulted as part of a shared decision making process, while screening is not recommended for patients aged ≥ 70 years.
Pathway flow maps also provide information about diagnostic standards, evaluation of the newly diagnosed, risk stratification, molecular testing, and end-of-life care.
Goodman says the pathway is now integrated into the VA electronic health record system via a template so clinicians can easily document pathway use. This allows the VA to track the use of the pathways locally, regionally, and nationally track the use of the pathways.
Clinicians are not mandated to follow every step in the pathway, but Goodman said the goal is > 80% adherence. If clinicians follow the standards, he said, “you’re considering efficacy, safety, and cost for that veteran.”
Prospective data suggests that adherence to the pathway eliminates certain disparities. African American veterans, for example, are as well-represented or even better represented than White veterans in prostate cancer care when pathways are followed.
Why might clinicians veer from the pathway? “If you’re seeing a patient who was treated in the community with drug X, but drug Y is chosen by the pathway, you can carry on with the previous care.” Alternatively, in some cases, patients may not tolerate the pathway standard, Goodman noted.
Goodman reports that he consults the pathway every day. “It’s helped standardize the care I provide to ensure there’s no gaps in how I’m treating patients.”
The newly updated US Department of Veterans Affairs (VA) prostate cancer clinical pathway looks like a set of guidelines, but it’s really something unique. As attendees learned at an Association of VA Hematology/Oncology (AVAHO) regional meeting in Detroit in June, the clinical pathways are designed to point the way toward a standard ideal treatment for the majority of cases, not just to suggest a number of possible options.
“Pathways will always offer one scenario. They try to get oncologists to practice in a similar fashion so things can be managed more uniformly,” Michael M. Goodman, MD, told Federal Practitioner prior to the AVAHO meeting that was focused on prostate cancer care. Goodman is an associate professor of medicine with Atrium Health Wake Forest Baptist Medical Center and helped develop the VA genitourinary oncology pathways.
“The overall goal is not just to standardize care as much as possible but also to synthesize the best and most cost-effective practices,” Goodman said. For example, “If you have 5 different therapies, and they all have about the same efficacy and safety, and 1 is less costly than the other 4, then it would make sense to choose that.”
The VA has offered pathways for multiple types of cancer since 2021, and the pathway for prostate cancer is among the most comprehensive. The VA system updated the pathway in March 2024, is available online both via SharePoint and externally.
“It goes through the entire gamut from screening, diagnosis, and management to end of life,” Goodman explained. Multiple disciplines, from primary care and surgery to genetics and imaging, can rely on the pathway to assist decision-making.
In terms of screening, the pathway offers a flow map guiding the screening choices. In patients aged ≤ 54 years, only certain high-risk groups, such as African Americans and those with a family history of prostate cancer, should be screened. From ages 54 to 69 years, patients should be consulted as part of a shared decision making process, while screening is not recommended for patients aged ≥ 70 years.
Pathway flow maps also provide information about diagnostic standards, evaluation of the newly diagnosed, risk stratification, molecular testing, and end-of-life care.
Goodman says the pathway is now integrated into the VA electronic health record system via a template so clinicians can easily document pathway use. This allows the VA to track the use of the pathways locally, regionally, and nationally track the use of the pathways.
Clinicians are not mandated to follow every step in the pathway, but Goodman said the goal is > 80% adherence. If clinicians follow the standards, he said, “you’re considering efficacy, safety, and cost for that veteran.”
Prospective data suggests that adherence to the pathway eliminates certain disparities. African American veterans, for example, are as well-represented or even better represented than White veterans in prostate cancer care when pathways are followed.
Why might clinicians veer from the pathway? “If you’re seeing a patient who was treated in the community with drug X, but drug Y is chosen by the pathway, you can carry on with the previous care.” Alternatively, in some cases, patients may not tolerate the pathway standard, Goodman noted.
Goodman reports that he consults the pathway every day. “It’s helped standardize the care I provide to ensure there’s no gaps in how I’m treating patients.”
The newly updated US Department of Veterans Affairs (VA) prostate cancer clinical pathway looks like a set of guidelines, but it’s really something unique. As attendees learned at an Association of VA Hematology/Oncology (AVAHO) regional meeting in Detroit in June, the clinical pathways are designed to point the way toward a standard ideal treatment for the majority of cases, not just to suggest a number of possible options.
“Pathways will always offer one scenario. They try to get oncologists to practice in a similar fashion so things can be managed more uniformly,” Michael M. Goodman, MD, told Federal Practitioner prior to the AVAHO meeting that was focused on prostate cancer care. Goodman is an associate professor of medicine with Atrium Health Wake Forest Baptist Medical Center and helped develop the VA genitourinary oncology pathways.
“The overall goal is not just to standardize care as much as possible but also to synthesize the best and most cost-effective practices,” Goodman said. For example, “If you have 5 different therapies, and they all have about the same efficacy and safety, and 1 is less costly than the other 4, then it would make sense to choose that.”
The VA has offered pathways for multiple types of cancer since 2021, and the pathway for prostate cancer is among the most comprehensive. The VA system updated the pathway in March 2024, is available online both via SharePoint and externally.
“It goes through the entire gamut from screening, diagnosis, and management to end of life,” Goodman explained. Multiple disciplines, from primary care and surgery to genetics and imaging, can rely on the pathway to assist decision-making.
In terms of screening, the pathway offers a flow map guiding the screening choices. In patients aged ≤ 54 years, only certain high-risk groups, such as African Americans and those with a family history of prostate cancer, should be screened. From ages 54 to 69 years, patients should be consulted as part of a shared decision making process, while screening is not recommended for patients aged ≥ 70 years.
Pathway flow maps also provide information about diagnostic standards, evaluation of the newly diagnosed, risk stratification, molecular testing, and end-of-life care.
Goodman says the pathway is now integrated into the VA electronic health record system via a template so clinicians can easily document pathway use. This allows the VA to track the use of the pathways locally, regionally, and nationally track the use of the pathways.
Clinicians are not mandated to follow every step in the pathway, but Goodman said the goal is > 80% adherence. If clinicians follow the standards, he said, “you’re considering efficacy, safety, and cost for that veteran.”
Prospective data suggests that adherence to the pathway eliminates certain disparities. African American veterans, for example, are as well-represented or even better represented than White veterans in prostate cancer care when pathways are followed.
Why might clinicians veer from the pathway? “If you’re seeing a patient who was treated in the community with drug X, but drug Y is chosen by the pathway, you can carry on with the previous care.” Alternatively, in some cases, patients may not tolerate the pathway standard, Goodman noted.
Goodman reports that he consults the pathway every day. “It’s helped standardize the care I provide to ensure there’s no gaps in how I’m treating patients.”
Neck Pain in Migraine Is Common, Linked to More Disability
, an international, prospective, cross-sectional study finds.
Of 51,969 respondents with headache over the past year, the 27.9% with migraine were more likely to have neck pain than those with non-migraine headache (68.3% vs 36.1%, respectively, P < .001), reported Richard B. Lipton, MD, professor of neurology at Albert Einstein College of Medicine, New York City, and colleagues in Headache.
Compared with other patients with migraine, those who also have neck pain have “greater disability, more psychiatric comorbidities, more allodynia, diminished quality of life, decreased work productivity, and reduced response to treatment,” Dr. Lipton said in an interview. “If patients don’t report [neck pain], it is probably worth asking about. And when patients have both migraine and neck pain, they may merit increased therapeutic attention.”
As Dr. Lipton noted, clinicians have long known that neck pain is common in migraine, although it’s been unclear how the two conditions are connected. “One possibility is that the neck pain is actually a manifestation of the migraine headache. Another possibility is that the neck pain is an independent factor unrelated to migraine headaches: Many people have migraine and cervical spine disease. And the third possibility is that neck pain may be an exacerbating factor, that cervical spine disease may make the migraine worse.”
Referred pain is a potential factor too, he said.
Assessing Migraine, Neck Pain, and Disability
The new study sought to better understand the role of neck pain in migraine, Dr. Lipton said.
For the CaMEO-I study, researchers surveyed 51,969 adults with headache via the Internet in Canada, France, Germany, Japan, United Kingdom, and the United States from 2021-2022. Most of the 37,477 patients with non-migraine headaches were considered to have tension headaches.
Among the 14,492 patients with migraine, demographics were statistically similar among those who had neck pain or didn’t have it (average age = 40.7 and 42.1, 68.4% and 72.5% female, and average BMIs = 26.0 and 26.4, respectively).
Among patients in the US, 71.4% of patients with migraine reported neck pain versus 35.9% of those with non-migraine headaches. In Canada, the numbers were 69.5% and 37.5%, respectively.
Among all patients with migraine, moderate-to-severe disability was more common among those with neck pain than those without neck pain (47.7% vs 28.9%, respectively, P < .001). Those with both migraine and neck pain had more symptom burden (P < .001), and 28.4% said neck pain was their most bothersome symptom. They also had a higher number of symptoms (P < .001).
Several conditions were more common among patients with migraine who reported neck pain versus those who didn’t (depression/anxiety, 40.2% vs 28.2%; anxiety, 41.2% vs 29.2%; and allodynia, 54.0% vs 36.6%, respectively, all P < 0.001). Those with neck pain were also more likely to have “poor acute treatment optimization” (61.1% vs 53.3%, respectively, P < .001).
Researchers noted limitations such as the use of self-reported data, the potential for selection bias, limitations regarding survey questions, and an inability to determine causation.
Clinical Messages
The findings suggest that patients with both migraine and neck pain have greater activation of second-order neurons in the trigeminocervical complex, Dr. Lipton said.
He added that neck pain is often part of the migraine prodrome or the migraine attack itself, suggesting that it’s “part and parcel of the migraine attack.” However, neck pain may have another cause — such as degenerative disease of the neck — if it’s not directly connected to migraine, he added.
As for clinical messages from the study, “it’s quite likely that the neck pain is a primary manifestation of migraine. Migraine may well be the explanation in the absence of a reason to look further,” Dr. Lipton said.
If neck pain heralds a migraine, treating the prodrome with CGRP receptor antagonists (“gepants”) can be helpful, he said. He highlighted other preventive options include beta blockers, anti-epilepsy drugs, and monoclonal antibodies. There’s also anecdotal support for using botulinum toxin A in patients with chronic migraine and neck pain, he said.
In an interview, Mayo Clinic Arizona associate professor of neurology Rashmi B. Halker Singh, MD, who’s familiar with the study but did not take part in it, praised the research. The findings “help us to better understand the impact of living with neck pain if you are somebody with migraine,” she said. “It alerts us that we need to be more aggressive in how we manage that in patients.”
The study also emphasizes the importance of preventive medication in appropriate patients with migraine, especially those with neck pain who may be living with greater disability, she said. “About 13% of people with migraine are on a preventive medication, but about 40% are eligible. That’s an area where we have a big gap.”
Dr. Halker Singh added that non-medication strategies such as acupuncture and physical therapy can be helpful.
AbbVie funded the study. Dr. Lipton reports support for the study from AbbVie; research support paid to his institution from the Czap Foundation, National Headache Foundation, National Institutes of Health, S&L Marx Foundation, and US Food and Drug Administration; and personal fees from AbbVie/Allergan, American Academy of Neurology, American Headache Society, Amgen, Biohaven, Biovision, Boston, Dr. Reddy’s (Promius), electroCore, Eli Lilly, GlaxoSmithKline, Grifols, Lundbeck (Alder), Merck, Pernix, Pfizer, Teva, Vector, and Vedanta Research. He holds stock/options in Axon, Biohaven, CoolTech, and Manistee. Other authors report various disclosures.
Dr. Halker Singh is deputy editor of Headache, where the study was published, but wasn’t aware of it until it was published.
, an international, prospective, cross-sectional study finds.
Of 51,969 respondents with headache over the past year, the 27.9% with migraine were more likely to have neck pain than those with non-migraine headache (68.3% vs 36.1%, respectively, P < .001), reported Richard B. Lipton, MD, professor of neurology at Albert Einstein College of Medicine, New York City, and colleagues in Headache.
Compared with other patients with migraine, those who also have neck pain have “greater disability, more psychiatric comorbidities, more allodynia, diminished quality of life, decreased work productivity, and reduced response to treatment,” Dr. Lipton said in an interview. “If patients don’t report [neck pain], it is probably worth asking about. And when patients have both migraine and neck pain, they may merit increased therapeutic attention.”
As Dr. Lipton noted, clinicians have long known that neck pain is common in migraine, although it’s been unclear how the two conditions are connected. “One possibility is that the neck pain is actually a manifestation of the migraine headache. Another possibility is that the neck pain is an independent factor unrelated to migraine headaches: Many people have migraine and cervical spine disease. And the third possibility is that neck pain may be an exacerbating factor, that cervical spine disease may make the migraine worse.”
Referred pain is a potential factor too, he said.
Assessing Migraine, Neck Pain, and Disability
The new study sought to better understand the role of neck pain in migraine, Dr. Lipton said.
For the CaMEO-I study, researchers surveyed 51,969 adults with headache via the Internet in Canada, France, Germany, Japan, United Kingdom, and the United States from 2021-2022. Most of the 37,477 patients with non-migraine headaches were considered to have tension headaches.
Among the 14,492 patients with migraine, demographics were statistically similar among those who had neck pain or didn’t have it (average age = 40.7 and 42.1, 68.4% and 72.5% female, and average BMIs = 26.0 and 26.4, respectively).
Among patients in the US, 71.4% of patients with migraine reported neck pain versus 35.9% of those with non-migraine headaches. In Canada, the numbers were 69.5% and 37.5%, respectively.
Among all patients with migraine, moderate-to-severe disability was more common among those with neck pain than those without neck pain (47.7% vs 28.9%, respectively, P < .001). Those with both migraine and neck pain had more symptom burden (P < .001), and 28.4% said neck pain was their most bothersome symptom. They also had a higher number of symptoms (P < .001).
Several conditions were more common among patients with migraine who reported neck pain versus those who didn’t (depression/anxiety, 40.2% vs 28.2%; anxiety, 41.2% vs 29.2%; and allodynia, 54.0% vs 36.6%, respectively, all P < 0.001). Those with neck pain were also more likely to have “poor acute treatment optimization” (61.1% vs 53.3%, respectively, P < .001).
Researchers noted limitations such as the use of self-reported data, the potential for selection bias, limitations regarding survey questions, and an inability to determine causation.
Clinical Messages
The findings suggest that patients with both migraine and neck pain have greater activation of second-order neurons in the trigeminocervical complex, Dr. Lipton said.
He added that neck pain is often part of the migraine prodrome or the migraine attack itself, suggesting that it’s “part and parcel of the migraine attack.” However, neck pain may have another cause — such as degenerative disease of the neck — if it’s not directly connected to migraine, he added.
As for clinical messages from the study, “it’s quite likely that the neck pain is a primary manifestation of migraine. Migraine may well be the explanation in the absence of a reason to look further,” Dr. Lipton said.
If neck pain heralds a migraine, treating the prodrome with CGRP receptor antagonists (“gepants”) can be helpful, he said. He highlighted other preventive options include beta blockers, anti-epilepsy drugs, and monoclonal antibodies. There’s also anecdotal support for using botulinum toxin A in patients with chronic migraine and neck pain, he said.
In an interview, Mayo Clinic Arizona associate professor of neurology Rashmi B. Halker Singh, MD, who’s familiar with the study but did not take part in it, praised the research. The findings “help us to better understand the impact of living with neck pain if you are somebody with migraine,” she said. “It alerts us that we need to be more aggressive in how we manage that in patients.”
The study also emphasizes the importance of preventive medication in appropriate patients with migraine, especially those with neck pain who may be living with greater disability, she said. “About 13% of people with migraine are on a preventive medication, but about 40% are eligible. That’s an area where we have a big gap.”
Dr. Halker Singh added that non-medication strategies such as acupuncture and physical therapy can be helpful.
AbbVie funded the study. Dr. Lipton reports support for the study from AbbVie; research support paid to his institution from the Czap Foundation, National Headache Foundation, National Institutes of Health, S&L Marx Foundation, and US Food and Drug Administration; and personal fees from AbbVie/Allergan, American Academy of Neurology, American Headache Society, Amgen, Biohaven, Biovision, Boston, Dr. Reddy’s (Promius), electroCore, Eli Lilly, GlaxoSmithKline, Grifols, Lundbeck (Alder), Merck, Pernix, Pfizer, Teva, Vector, and Vedanta Research. He holds stock/options in Axon, Biohaven, CoolTech, and Manistee. Other authors report various disclosures.
Dr. Halker Singh is deputy editor of Headache, where the study was published, but wasn’t aware of it until it was published.
, an international, prospective, cross-sectional study finds.
Of 51,969 respondents with headache over the past year, the 27.9% with migraine were more likely to have neck pain than those with non-migraine headache (68.3% vs 36.1%, respectively, P < .001), reported Richard B. Lipton, MD, professor of neurology at Albert Einstein College of Medicine, New York City, and colleagues in Headache.
Compared with other patients with migraine, those who also have neck pain have “greater disability, more psychiatric comorbidities, more allodynia, diminished quality of life, decreased work productivity, and reduced response to treatment,” Dr. Lipton said in an interview. “If patients don’t report [neck pain], it is probably worth asking about. And when patients have both migraine and neck pain, they may merit increased therapeutic attention.”
As Dr. Lipton noted, clinicians have long known that neck pain is common in migraine, although it’s been unclear how the two conditions are connected. “One possibility is that the neck pain is actually a manifestation of the migraine headache. Another possibility is that the neck pain is an independent factor unrelated to migraine headaches: Many people have migraine and cervical spine disease. And the third possibility is that neck pain may be an exacerbating factor, that cervical spine disease may make the migraine worse.”
Referred pain is a potential factor too, he said.
Assessing Migraine, Neck Pain, and Disability
The new study sought to better understand the role of neck pain in migraine, Dr. Lipton said.
For the CaMEO-I study, researchers surveyed 51,969 adults with headache via the Internet in Canada, France, Germany, Japan, United Kingdom, and the United States from 2021-2022. Most of the 37,477 patients with non-migraine headaches were considered to have tension headaches.
Among the 14,492 patients with migraine, demographics were statistically similar among those who had neck pain or didn’t have it (average age = 40.7 and 42.1, 68.4% and 72.5% female, and average BMIs = 26.0 and 26.4, respectively).
Among patients in the US, 71.4% of patients with migraine reported neck pain versus 35.9% of those with non-migraine headaches. In Canada, the numbers were 69.5% and 37.5%, respectively.
Among all patients with migraine, moderate-to-severe disability was more common among those with neck pain than those without neck pain (47.7% vs 28.9%, respectively, P < .001). Those with both migraine and neck pain had more symptom burden (P < .001), and 28.4% said neck pain was their most bothersome symptom. They also had a higher number of symptoms (P < .001).
Several conditions were more common among patients with migraine who reported neck pain versus those who didn’t (depression/anxiety, 40.2% vs 28.2%; anxiety, 41.2% vs 29.2%; and allodynia, 54.0% vs 36.6%, respectively, all P < 0.001). Those with neck pain were also more likely to have “poor acute treatment optimization” (61.1% vs 53.3%, respectively, P < .001).
Researchers noted limitations such as the use of self-reported data, the potential for selection bias, limitations regarding survey questions, and an inability to determine causation.
Clinical Messages
The findings suggest that patients with both migraine and neck pain have greater activation of second-order neurons in the trigeminocervical complex, Dr. Lipton said.
He added that neck pain is often part of the migraine prodrome or the migraine attack itself, suggesting that it’s “part and parcel of the migraine attack.” However, neck pain may have another cause — such as degenerative disease of the neck — if it’s not directly connected to migraine, he added.
As for clinical messages from the study, “it’s quite likely that the neck pain is a primary manifestation of migraine. Migraine may well be the explanation in the absence of a reason to look further,” Dr. Lipton said.
If neck pain heralds a migraine, treating the prodrome with CGRP receptor antagonists (“gepants”) can be helpful, he said. He highlighted other preventive options include beta blockers, anti-epilepsy drugs, and monoclonal antibodies. There’s also anecdotal support for using botulinum toxin A in patients with chronic migraine and neck pain, he said.
In an interview, Mayo Clinic Arizona associate professor of neurology Rashmi B. Halker Singh, MD, who’s familiar with the study but did not take part in it, praised the research. The findings “help us to better understand the impact of living with neck pain if you are somebody with migraine,” she said. “It alerts us that we need to be more aggressive in how we manage that in patients.”
The study also emphasizes the importance of preventive medication in appropriate patients with migraine, especially those with neck pain who may be living with greater disability, she said. “About 13% of people with migraine are on a preventive medication, but about 40% are eligible. That’s an area where we have a big gap.”
Dr. Halker Singh added that non-medication strategies such as acupuncture and physical therapy can be helpful.
AbbVie funded the study. Dr. Lipton reports support for the study from AbbVie; research support paid to his institution from the Czap Foundation, National Headache Foundation, National Institutes of Health, S&L Marx Foundation, and US Food and Drug Administration; and personal fees from AbbVie/Allergan, American Academy of Neurology, American Headache Society, Amgen, Biohaven, Biovision, Boston, Dr. Reddy’s (Promius), electroCore, Eli Lilly, GlaxoSmithKline, Grifols, Lundbeck (Alder), Merck, Pernix, Pfizer, Teva, Vector, and Vedanta Research. He holds stock/options in Axon, Biohaven, CoolTech, and Manistee. Other authors report various disclosures.
Dr. Halker Singh is deputy editor of Headache, where the study was published, but wasn’t aware of it until it was published.
FROM HEADACHE
Stroke Recurrence Risk Doubles in Patients With AF Who Stop Anticoagulation Therapy
, a new Danish nationwide cohort study finds.
Among 8,119 patients aged 50 years and older (54.1% male, mean age 78.4), 4.3% had a recurrent stroke within 1 year following discharge for the initial stroke, reported David Gaist, PhD, of Odense University Hospital, Odense, Denmark, and colleagues in JAMA Neurology.
An adjusted analysis found that those who stopped therapy were more than twice as likely to experience another stroke over a mean 2.9 years (13.4% vs 6.8%, adjusted odds ratio [aOR] = 2.13; 95% confidence interval [CI], 1.57-2.89).
The findings highlight the preventive power of OAC therapy, Dr. Gaist said in an interview, and point to the importance of counseling patients about the benefits of the drugs. “Clinicians can provide balanced information on the pros and cons of discontinuing oral anticoagulants as well as lay out plans on when to restart the medication,” he said.
The researchers launched the study “to provide data on how often recurrent ischemic strokes occur in a large, unselected cohort of patients with atrial fibrillation who had a stroke and started or restarted oral anticoagulants, a situation mirroring what we see in our everyday lives as clinicians,” Dr. Gaist said. “We also wanted to see if patients with breakthrough strokes had particular characteristics compared with patients who did not have a recurrent stroke. Finally, we wanted to quantify a very simple cause of breakthrough stroke by answering the following question: How many of these patients had stopped taking their oral anticoagulant?”
A Large, Unselected Patient Cohort
Dr. Gaist and colleagues tracked 8,119 patients with ischemic stroke and atrial fibrillation who started or restarted OAC therapy within 30 days following their discharge between 2014 and 2021. Patients either had atrial fibrillation before their stroke or developed it afterward.
Eighty-one percent of patients had hypertension, 19.7% had diabetes, and 27.3% had ischemic heart disease; 35.3% had never smoked and smoking information was missing for 15.9%. Race/ethnicity information was not provided.
Patients were followed for an average of 2.9 years until 2022, and all were alive at least 30 days after discharge. During that time, 663 patients had a recurrent ischemic stroke (4.3%), of whom 80.4% were on OAC therapy. The percentage who had stroke at 2 years rose to 6.5%.
While the researchers thought the number of strokes was high, Dr. Gaist said, this isn’t a sign that the drugs aren’t working. “Oral anticoagulant use in secondary prevention in atrial fibrillation is guideline-supported as it has been proven to reduce the risk of stroke by roughly two thirds.”
Of study participants at baseline, 37.9% took oral anticoagulants, 23.5% took direct oral anticoagulants (DOACs; dabigatran, rivaroxaban, apixaban, and edoxaban), and 15.1% took vitamin K antagonists. In a nested case-control analysis of 663 cases (58.7% men, mean age 80.1) matched to 2,652 controls, at admission for ischemic stroke, 80.4% were on OAC therapy, and 8%-11% of patients stopped OAC therapy after their strokes, the researchers reported.
Patients who stopped OAC therapy had more severe strokes than those who didn’t at 7 days (median recurrent ischemic stroke Scandinavian Stroke Scale [SSS] score = 40.0 vs 46.0, respectively; aOR = 2.10; 95% CI, 1.31-3.36). Those who stopped OAC therapy also had higher mortality rates at 7 days (11.2% vs 3.9%, respectively) and 30 days (28.1% vs 10.9%, respectively).
It’s not clear why some patients discontinued OAC therapy. “We looked for evidence of serious bleeding or surgical procedures around the time of anticoagulant discontinuation but found this only to be the case in roughly 10% of these patients,” Dr. Gaist said.
He added that the study probably “underestimates the issue of anticoagulant discontinuation, particularly for DOACs, where a shorter half-life compared with warfarin means that even a short drug-break of a few days puts the patient at increased risk of stroke.”
The authors noted study limitations, including the lack of data on actual medication usage, alcohol usage, stroke etiology, lesion location, and socioeconomic status. And, they wrote, the study population is mostly of European origin.
No Surprises
Steven R. Messe, MD, professor of neurology at the Hospital of the University of Pennsylvania, Philadelphia, who didn’t take part in the study but is familiar with its findings, said in an interview that the study is a “well-done analysis.”
The findings are not surprising, he said. “The overall risk of stroke recurrence was 4.3% at 1 year while the mortality rate was higher at 15.4%. Given that the median CHA2DS2-VASc score was 4 and the average age was 79, the stroke recurrence rate and mortality rate are in line with prior studies.”
In regard to the power of OAC therapy to prevent recurrent strokes, Dr. Messe noted that patients may not be adhering to prescribed regimens. Also, “while DOACs are clearly safer that vitamin K–dependent anticoagulants, the medications are generally not dose adjusted. It is possible that adjusting the dose based on measured anti-Xa levels to insure therapeutic anticoagulant effects may reduce the stroke risk further.”
He added that “most of these patients with prior stroke and atrial fibrillation are vasculopathic and at risk of additional strokes due to other mechanisms such as small vessel or large vessel disease.”
In the big picture, the study “confirms again that anticoagulation should be prescribed to all patients with atrial fibrillation and prior stroke, unless there is a strong bleeding risk contraindication,” Dr. Messe said. These patients are clearly at high risk of stroke recurrence and mortality, and all risk factors should be aggressively managed.”
Researchers are exploring other options, he said. “For example, there are studies of factor XI inhibitors that could be added to a DOAC for additional reductions in ischemic stroke. In addition, in patients undergoing cardiac surgery, the randomized trial LAOS III demonstrated that surgical left atrial occlusion in addition to anticoagulation may provide additional stroke prevention.”
Dr. Gaist disclosed personal fees from Pfizer and Bristol Myers Squibb, and grants from Bayer. Several other authors reported various relationships with industry. Dr. Messe has no disclosures.
, a new Danish nationwide cohort study finds.
Among 8,119 patients aged 50 years and older (54.1% male, mean age 78.4), 4.3% had a recurrent stroke within 1 year following discharge for the initial stroke, reported David Gaist, PhD, of Odense University Hospital, Odense, Denmark, and colleagues in JAMA Neurology.
An adjusted analysis found that those who stopped therapy were more than twice as likely to experience another stroke over a mean 2.9 years (13.4% vs 6.8%, adjusted odds ratio [aOR] = 2.13; 95% confidence interval [CI], 1.57-2.89).
The findings highlight the preventive power of OAC therapy, Dr. Gaist said in an interview, and point to the importance of counseling patients about the benefits of the drugs. “Clinicians can provide balanced information on the pros and cons of discontinuing oral anticoagulants as well as lay out plans on when to restart the medication,” he said.
The researchers launched the study “to provide data on how often recurrent ischemic strokes occur in a large, unselected cohort of patients with atrial fibrillation who had a stroke and started or restarted oral anticoagulants, a situation mirroring what we see in our everyday lives as clinicians,” Dr. Gaist said. “We also wanted to see if patients with breakthrough strokes had particular characteristics compared with patients who did not have a recurrent stroke. Finally, we wanted to quantify a very simple cause of breakthrough stroke by answering the following question: How many of these patients had stopped taking their oral anticoagulant?”
A Large, Unselected Patient Cohort
Dr. Gaist and colleagues tracked 8,119 patients with ischemic stroke and atrial fibrillation who started or restarted OAC therapy within 30 days following their discharge between 2014 and 2021. Patients either had atrial fibrillation before their stroke or developed it afterward.
Eighty-one percent of patients had hypertension, 19.7% had diabetes, and 27.3% had ischemic heart disease; 35.3% had never smoked and smoking information was missing for 15.9%. Race/ethnicity information was not provided.
Patients were followed for an average of 2.9 years until 2022, and all were alive at least 30 days after discharge. During that time, 663 patients had a recurrent ischemic stroke (4.3%), of whom 80.4% were on OAC therapy. The percentage who had stroke at 2 years rose to 6.5%.
While the researchers thought the number of strokes was high, Dr. Gaist said, this isn’t a sign that the drugs aren’t working. “Oral anticoagulant use in secondary prevention in atrial fibrillation is guideline-supported as it has been proven to reduce the risk of stroke by roughly two thirds.”
Of study participants at baseline, 37.9% took oral anticoagulants, 23.5% took direct oral anticoagulants (DOACs; dabigatran, rivaroxaban, apixaban, and edoxaban), and 15.1% took vitamin K antagonists. In a nested case-control analysis of 663 cases (58.7% men, mean age 80.1) matched to 2,652 controls, at admission for ischemic stroke, 80.4% were on OAC therapy, and 8%-11% of patients stopped OAC therapy after their strokes, the researchers reported.
Patients who stopped OAC therapy had more severe strokes than those who didn’t at 7 days (median recurrent ischemic stroke Scandinavian Stroke Scale [SSS] score = 40.0 vs 46.0, respectively; aOR = 2.10; 95% CI, 1.31-3.36). Those who stopped OAC therapy also had higher mortality rates at 7 days (11.2% vs 3.9%, respectively) and 30 days (28.1% vs 10.9%, respectively).
It’s not clear why some patients discontinued OAC therapy. “We looked for evidence of serious bleeding or surgical procedures around the time of anticoagulant discontinuation but found this only to be the case in roughly 10% of these patients,” Dr. Gaist said.
He added that the study probably “underestimates the issue of anticoagulant discontinuation, particularly for DOACs, where a shorter half-life compared with warfarin means that even a short drug-break of a few days puts the patient at increased risk of stroke.”
The authors noted study limitations, including the lack of data on actual medication usage, alcohol usage, stroke etiology, lesion location, and socioeconomic status. And, they wrote, the study population is mostly of European origin.
No Surprises
Steven R. Messe, MD, professor of neurology at the Hospital of the University of Pennsylvania, Philadelphia, who didn’t take part in the study but is familiar with its findings, said in an interview that the study is a “well-done analysis.”
The findings are not surprising, he said. “The overall risk of stroke recurrence was 4.3% at 1 year while the mortality rate was higher at 15.4%. Given that the median CHA2DS2-VASc score was 4 and the average age was 79, the stroke recurrence rate and mortality rate are in line with prior studies.”
In regard to the power of OAC therapy to prevent recurrent strokes, Dr. Messe noted that patients may not be adhering to prescribed regimens. Also, “while DOACs are clearly safer that vitamin K–dependent anticoagulants, the medications are generally not dose adjusted. It is possible that adjusting the dose based on measured anti-Xa levels to insure therapeutic anticoagulant effects may reduce the stroke risk further.”
He added that “most of these patients with prior stroke and atrial fibrillation are vasculopathic and at risk of additional strokes due to other mechanisms such as small vessel or large vessel disease.”
In the big picture, the study “confirms again that anticoagulation should be prescribed to all patients with atrial fibrillation and prior stroke, unless there is a strong bleeding risk contraindication,” Dr. Messe said. These patients are clearly at high risk of stroke recurrence and mortality, and all risk factors should be aggressively managed.”
Researchers are exploring other options, he said. “For example, there are studies of factor XI inhibitors that could be added to a DOAC for additional reductions in ischemic stroke. In addition, in patients undergoing cardiac surgery, the randomized trial LAOS III demonstrated that surgical left atrial occlusion in addition to anticoagulation may provide additional stroke prevention.”
Dr. Gaist disclosed personal fees from Pfizer and Bristol Myers Squibb, and grants from Bayer. Several other authors reported various relationships with industry. Dr. Messe has no disclosures.
, a new Danish nationwide cohort study finds.
Among 8,119 patients aged 50 years and older (54.1% male, mean age 78.4), 4.3% had a recurrent stroke within 1 year following discharge for the initial stroke, reported David Gaist, PhD, of Odense University Hospital, Odense, Denmark, and colleagues in JAMA Neurology.
An adjusted analysis found that those who stopped therapy were more than twice as likely to experience another stroke over a mean 2.9 years (13.4% vs 6.8%, adjusted odds ratio [aOR] = 2.13; 95% confidence interval [CI], 1.57-2.89).
The findings highlight the preventive power of OAC therapy, Dr. Gaist said in an interview, and point to the importance of counseling patients about the benefits of the drugs. “Clinicians can provide balanced information on the pros and cons of discontinuing oral anticoagulants as well as lay out plans on when to restart the medication,” he said.
The researchers launched the study “to provide data on how often recurrent ischemic strokes occur in a large, unselected cohort of patients with atrial fibrillation who had a stroke and started or restarted oral anticoagulants, a situation mirroring what we see in our everyday lives as clinicians,” Dr. Gaist said. “We also wanted to see if patients with breakthrough strokes had particular characteristics compared with patients who did not have a recurrent stroke. Finally, we wanted to quantify a very simple cause of breakthrough stroke by answering the following question: How many of these patients had stopped taking their oral anticoagulant?”
A Large, Unselected Patient Cohort
Dr. Gaist and colleagues tracked 8,119 patients with ischemic stroke and atrial fibrillation who started or restarted OAC therapy within 30 days following their discharge between 2014 and 2021. Patients either had atrial fibrillation before their stroke or developed it afterward.
Eighty-one percent of patients had hypertension, 19.7% had diabetes, and 27.3% had ischemic heart disease; 35.3% had never smoked and smoking information was missing for 15.9%. Race/ethnicity information was not provided.
Patients were followed for an average of 2.9 years until 2022, and all were alive at least 30 days after discharge. During that time, 663 patients had a recurrent ischemic stroke (4.3%), of whom 80.4% were on OAC therapy. The percentage who had stroke at 2 years rose to 6.5%.
While the researchers thought the number of strokes was high, Dr. Gaist said, this isn’t a sign that the drugs aren’t working. “Oral anticoagulant use in secondary prevention in atrial fibrillation is guideline-supported as it has been proven to reduce the risk of stroke by roughly two thirds.”
Of study participants at baseline, 37.9% took oral anticoagulants, 23.5% took direct oral anticoagulants (DOACs; dabigatran, rivaroxaban, apixaban, and edoxaban), and 15.1% took vitamin K antagonists. In a nested case-control analysis of 663 cases (58.7% men, mean age 80.1) matched to 2,652 controls, at admission for ischemic stroke, 80.4% were on OAC therapy, and 8%-11% of patients stopped OAC therapy after their strokes, the researchers reported.
Patients who stopped OAC therapy had more severe strokes than those who didn’t at 7 days (median recurrent ischemic stroke Scandinavian Stroke Scale [SSS] score = 40.0 vs 46.0, respectively; aOR = 2.10; 95% CI, 1.31-3.36). Those who stopped OAC therapy also had higher mortality rates at 7 days (11.2% vs 3.9%, respectively) and 30 days (28.1% vs 10.9%, respectively).
It’s not clear why some patients discontinued OAC therapy. “We looked for evidence of serious bleeding or surgical procedures around the time of anticoagulant discontinuation but found this only to be the case in roughly 10% of these patients,” Dr. Gaist said.
He added that the study probably “underestimates the issue of anticoagulant discontinuation, particularly for DOACs, where a shorter half-life compared with warfarin means that even a short drug-break of a few days puts the patient at increased risk of stroke.”
The authors noted study limitations, including the lack of data on actual medication usage, alcohol usage, stroke etiology, lesion location, and socioeconomic status. And, they wrote, the study population is mostly of European origin.
No Surprises
Steven R. Messe, MD, professor of neurology at the Hospital of the University of Pennsylvania, Philadelphia, who didn’t take part in the study but is familiar with its findings, said in an interview that the study is a “well-done analysis.”
The findings are not surprising, he said. “The overall risk of stroke recurrence was 4.3% at 1 year while the mortality rate was higher at 15.4%. Given that the median CHA2DS2-VASc score was 4 and the average age was 79, the stroke recurrence rate and mortality rate are in line with prior studies.”
In regard to the power of OAC therapy to prevent recurrent strokes, Dr. Messe noted that patients may not be adhering to prescribed regimens. Also, “while DOACs are clearly safer that vitamin K–dependent anticoagulants, the medications are generally not dose adjusted. It is possible that adjusting the dose based on measured anti-Xa levels to insure therapeutic anticoagulant effects may reduce the stroke risk further.”
He added that “most of these patients with prior stroke and atrial fibrillation are vasculopathic and at risk of additional strokes due to other mechanisms such as small vessel or large vessel disease.”
In the big picture, the study “confirms again that anticoagulation should be prescribed to all patients with atrial fibrillation and prior stroke, unless there is a strong bleeding risk contraindication,” Dr. Messe said. These patients are clearly at high risk of stroke recurrence and mortality, and all risk factors should be aggressively managed.”
Researchers are exploring other options, he said. “For example, there are studies of factor XI inhibitors that could be added to a DOAC for additional reductions in ischemic stroke. In addition, in patients undergoing cardiac surgery, the randomized trial LAOS III demonstrated that surgical left atrial occlusion in addition to anticoagulation may provide additional stroke prevention.”
Dr. Gaist disclosed personal fees from Pfizer and Bristol Myers Squibb, and grants from Bayer. Several other authors reported various relationships with industry. Dr. Messe has no disclosures.
FROM JAMA NEUROLOGY
AVAHO Mtg: Germline Testing Key for Vets With High-Risk PC
Not too long ago, prostate-cancer genetics didn’t mean much to patient care. But in recent years, the landscape of therapy has transformed as researchers have discovered links between multiple genes and aggressive tumors.
Now, as a hematologist-oncologist explained to attendees at an Association of VA Hematology/Oncology regional meeting in Detroit, genetic tests can guide treatment for some—but not all—men with prostate cancer.
For patients with mutations, appropriate supplemental medications “can improve overall outcomes and have a long-standing impact on patients” said Scott J. Dawsey, MD, of the John D. Dingell Veterans Affairs Medical Center in Detroit in an interview following the AVAHO meeting, which focused on the management of prostate cancer.
As Dawsey explained, about 10% of patients with prostate cancer appear to have genetic mutations, although the exact percentage is unclear. The mutations are especially common in metastatic forms of prostate cancer. They’re estimated to be present in 11.8%-16.2% of those cases.
While these proportions are relatively small, the number of overall prostate-cancer cases with mutations is large due to the high burden of the disease, Dawsey said. Prostate cancer is by far the most common cancer in men, and estimated 299,010 cases will be diagnosed in the United States this year.
According to Dawsey, genetic mutations seem to boost the risk of more aggressive disease—and the risk of other malignancies—by disrupting DNA repair. This process can lead to even more mutations that may “make the cancer behave and grow more aggressively.”
But not all prostate cancer patients need to undergo genetic testing. Dawsey urged colleagues to figure out which patients should be tested by consulting National Comprehensive Cancer Network (NCCN) guidelines and the newly updated US Department of Veterans Affairs (VA) prostate cancer clinical pathway.
The two sets of recommendations agree on germline testing in patients with cases that are metastatic, very high risk, and high risk. Lower-risk cases should only be tested if patients meet family history criteria. The sets of guidelines also recommend somatic testing in patients with metastatic cancer.
In addition to providing guidance about treatment, genetic test results can have implications regarding other potential malignancies that may affect patients, Dawsey said. The results may also have implications for cancer risk in family members.
Several drugs are now available for patients with genetic mutations, including checkpoint inhibitors and PARP inhibitors. The drugs, which have unique mechanisms of action, are given in addition to standard prostate cancer treatments, he said.
“If a patient doesn’t have one of these genetic changes,” he said, “these drugs aren’t an option.”
A long list of drugs or combinations of drugs are in clinical trials, including the poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitors olaparib, abiraterone, and niraparib and the checkpoint inhibitors nivolumab and cemiplimab.
The drugs generally improve response rates and progression-free survival, Dawsey said, and patients are generally able to tolerate them. In regard to which drugs to choose, he suggested consulting the and NCCN guidelines and the VA oncology clinical pathway for prostate cancer.
Not too long ago, prostate-cancer genetics didn’t mean much to patient care. But in recent years, the landscape of therapy has transformed as researchers have discovered links between multiple genes and aggressive tumors.
Now, as a hematologist-oncologist explained to attendees at an Association of VA Hematology/Oncology regional meeting in Detroit, genetic tests can guide treatment for some—but not all—men with prostate cancer.
For patients with mutations, appropriate supplemental medications “can improve overall outcomes and have a long-standing impact on patients” said Scott J. Dawsey, MD, of the John D. Dingell Veterans Affairs Medical Center in Detroit in an interview following the AVAHO meeting, which focused on the management of prostate cancer.
As Dawsey explained, about 10% of patients with prostate cancer appear to have genetic mutations, although the exact percentage is unclear. The mutations are especially common in metastatic forms of prostate cancer. They’re estimated to be present in 11.8%-16.2% of those cases.
While these proportions are relatively small, the number of overall prostate-cancer cases with mutations is large due to the high burden of the disease, Dawsey said. Prostate cancer is by far the most common cancer in men, and estimated 299,010 cases will be diagnosed in the United States this year.
According to Dawsey, genetic mutations seem to boost the risk of more aggressive disease—and the risk of other malignancies—by disrupting DNA repair. This process can lead to even more mutations that may “make the cancer behave and grow more aggressively.”
But not all prostate cancer patients need to undergo genetic testing. Dawsey urged colleagues to figure out which patients should be tested by consulting National Comprehensive Cancer Network (NCCN) guidelines and the newly updated US Department of Veterans Affairs (VA) prostate cancer clinical pathway.
The two sets of recommendations agree on germline testing in patients with cases that are metastatic, very high risk, and high risk. Lower-risk cases should only be tested if patients meet family history criteria. The sets of guidelines also recommend somatic testing in patients with metastatic cancer.
In addition to providing guidance about treatment, genetic test results can have implications regarding other potential malignancies that may affect patients, Dawsey said. The results may also have implications for cancer risk in family members.
Several drugs are now available for patients with genetic mutations, including checkpoint inhibitors and PARP inhibitors. The drugs, which have unique mechanisms of action, are given in addition to standard prostate cancer treatments, he said.
“If a patient doesn’t have one of these genetic changes,” he said, “these drugs aren’t an option.”
A long list of drugs or combinations of drugs are in clinical trials, including the poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitors olaparib, abiraterone, and niraparib and the checkpoint inhibitors nivolumab and cemiplimab.
The drugs generally improve response rates and progression-free survival, Dawsey said, and patients are generally able to tolerate them. In regard to which drugs to choose, he suggested consulting the and NCCN guidelines and the VA oncology clinical pathway for prostate cancer.
Not too long ago, prostate-cancer genetics didn’t mean much to patient care. But in recent years, the landscape of therapy has transformed as researchers have discovered links between multiple genes and aggressive tumors.
Now, as a hematologist-oncologist explained to attendees at an Association of VA Hematology/Oncology regional meeting in Detroit, genetic tests can guide treatment for some—but not all—men with prostate cancer.
For patients with mutations, appropriate supplemental medications “can improve overall outcomes and have a long-standing impact on patients” said Scott J. Dawsey, MD, of the John D. Dingell Veterans Affairs Medical Center in Detroit in an interview following the AVAHO meeting, which focused on the management of prostate cancer.
As Dawsey explained, about 10% of patients with prostate cancer appear to have genetic mutations, although the exact percentage is unclear. The mutations are especially common in metastatic forms of prostate cancer. They’re estimated to be present in 11.8%-16.2% of those cases.
While these proportions are relatively small, the number of overall prostate-cancer cases with mutations is large due to the high burden of the disease, Dawsey said. Prostate cancer is by far the most common cancer in men, and estimated 299,010 cases will be diagnosed in the United States this year.
According to Dawsey, genetic mutations seem to boost the risk of more aggressive disease—and the risk of other malignancies—by disrupting DNA repair. This process can lead to even more mutations that may “make the cancer behave and grow more aggressively.”
But not all prostate cancer patients need to undergo genetic testing. Dawsey urged colleagues to figure out which patients should be tested by consulting National Comprehensive Cancer Network (NCCN) guidelines and the newly updated US Department of Veterans Affairs (VA) prostate cancer clinical pathway.
The two sets of recommendations agree on germline testing in patients with cases that are metastatic, very high risk, and high risk. Lower-risk cases should only be tested if patients meet family history criteria. The sets of guidelines also recommend somatic testing in patients with metastatic cancer.
In addition to providing guidance about treatment, genetic test results can have implications regarding other potential malignancies that may affect patients, Dawsey said. The results may also have implications for cancer risk in family members.
Several drugs are now available for patients with genetic mutations, including checkpoint inhibitors and PARP inhibitors. The drugs, which have unique mechanisms of action, are given in addition to standard prostate cancer treatments, he said.
“If a patient doesn’t have one of these genetic changes,” he said, “these drugs aren’t an option.”
A long list of drugs or combinations of drugs are in clinical trials, including the poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitors olaparib, abiraterone, and niraparib and the checkpoint inhibitors nivolumab and cemiplimab.
The drugs generally improve response rates and progression-free survival, Dawsey said, and patients are generally able to tolerate them. In regard to which drugs to choose, he suggested consulting the and NCCN guidelines and the VA oncology clinical pathway for prostate cancer.
CMS Announces End to Cyberattack Relief Program
The Centers for Medicare & Medicaid Services (CMS) has announced the conclusion of a program that provided billions in early Medicare payments to those affected by the Change Healthcare/UnitedHealth Group cyberattack last winter.
CMS reported that the program advanced more than $2.55 billion in Medicare payments to > 4200 Part A providers, including hospitals, and more than $717.18 million in payments to Part B suppliers such as physicians, nonphysician practitioners, and durable medical equipment suppliers.
According to CMS, the Medicare billing system is now functioning properly, and 96% of the early payments have been recovered. The advances were to represent ≤ 30 days of typical claims payments in a 3-month period of 2023, with full repayment expected within 90 days through “automatic recoupment from Medicare claims” — no extensions allowed.
The agency took a victory lap regarding its response. “In the face of one of the most widespread cyberattacks on the US health care industry, CMS promptly took action to get providers and suppliers access to the funds they needed to continue providing patients with vital care,” CMS Administrator Chiquita Brooks-LaSure said in a statement. “Our efforts helped minimize the disruptive fallout from this incident, and we will remain vigilant to be ready to address future events.”
Ongoing Concerns from Health Care Organizations
Ben Teicher, an American Hospital Association spokesman, said that the organization hopes that CMS will be responsive if there’s more need for action after the advance payment program expires. The organization represents about 5000 hospitals, health care systems, and other providers.
“Our members report that the aftereffects of this event will likely be felt throughout the remainder of the year,” he said. According to Teicher, hospitals remain concerned about their ability to process claims and appeal denials, the safety of reconnecting to cyber services, and access to information needed to bill patients and reconcile payments.
In addition, hospitals are concerned about “financial support to mitigate the considerable costs incurred as a result of the cyberattack,” he said.
Charlene MacDonald, executive vice-president of public affairs at the Federation of American Hospitals, which represents more than 1000 for-profit hospitals, sent a statement to this news organization that said some providers “are still feeling the effects of care denials and delays caused by insurer inaction.
“We appreciate that the Administration acted within its authority to support providers during this unprecedented crisis and blunt these devastating impacts, especially because a vast majority of managed care companies failed to step up to the plate,” she said. “It is now time to shift our focus to holding plans accountable for using tactics to delay and deny needed patient care.”
Cyberattack Impact and Response
The ransom-based cyberattack against Change Healthcare/UnitedHealth Group targeted an electronic data interchange clearing house processing payer reimbursement systems, disrupting cash flows at hospitals and medical practices, and affecting patient access to prescriptions and life-saving therapy.
Change Healthcare — part of the UnitedHealth Group subsidiary Optum — processes half of all medical claims, according to a Department of Justice lawsuit. The American Hospital Association described the cyberattack as “the most significant and consequential incident of its kind” in US history.
By late March, UnitedHealth Group said nearly all medical and pharmacy claims were processing properly, while a deputy secretary of the US Department of Health & Human Services told clinicians that officials were focusing on the last group of clinicians who were facing cash-flow problems.
Still, a senior advisor with CMS told providers at that time that “we have heard from so many providers over the last several weeks who are really struggling to make ends meet right now or who are worried that they will not be able to make payroll in the weeks to come.”
Randy Dotinga is a freelance health/medical reporter and board member of the Association of Health Care Journalists.
A version of this article appeared on Medscape.com.
The Centers for Medicare & Medicaid Services (CMS) has announced the conclusion of a program that provided billions in early Medicare payments to those affected by the Change Healthcare/UnitedHealth Group cyberattack last winter.
CMS reported that the program advanced more than $2.55 billion in Medicare payments to > 4200 Part A providers, including hospitals, and more than $717.18 million in payments to Part B suppliers such as physicians, nonphysician practitioners, and durable medical equipment suppliers.
According to CMS, the Medicare billing system is now functioning properly, and 96% of the early payments have been recovered. The advances were to represent ≤ 30 days of typical claims payments in a 3-month period of 2023, with full repayment expected within 90 days through “automatic recoupment from Medicare claims” — no extensions allowed.
The agency took a victory lap regarding its response. “In the face of one of the most widespread cyberattacks on the US health care industry, CMS promptly took action to get providers and suppliers access to the funds they needed to continue providing patients with vital care,” CMS Administrator Chiquita Brooks-LaSure said in a statement. “Our efforts helped minimize the disruptive fallout from this incident, and we will remain vigilant to be ready to address future events.”
Ongoing Concerns from Health Care Organizations
Ben Teicher, an American Hospital Association spokesman, said that the organization hopes that CMS will be responsive if there’s more need for action after the advance payment program expires. The organization represents about 5000 hospitals, health care systems, and other providers.
“Our members report that the aftereffects of this event will likely be felt throughout the remainder of the year,” he said. According to Teicher, hospitals remain concerned about their ability to process claims and appeal denials, the safety of reconnecting to cyber services, and access to information needed to bill patients and reconcile payments.
In addition, hospitals are concerned about “financial support to mitigate the considerable costs incurred as a result of the cyberattack,” he said.
Charlene MacDonald, executive vice-president of public affairs at the Federation of American Hospitals, which represents more than 1000 for-profit hospitals, sent a statement to this news organization that said some providers “are still feeling the effects of care denials and delays caused by insurer inaction.
“We appreciate that the Administration acted within its authority to support providers during this unprecedented crisis and blunt these devastating impacts, especially because a vast majority of managed care companies failed to step up to the plate,” she said. “It is now time to shift our focus to holding plans accountable for using tactics to delay and deny needed patient care.”
Cyberattack Impact and Response
The ransom-based cyberattack against Change Healthcare/UnitedHealth Group targeted an electronic data interchange clearing house processing payer reimbursement systems, disrupting cash flows at hospitals and medical practices, and affecting patient access to prescriptions and life-saving therapy.
Change Healthcare — part of the UnitedHealth Group subsidiary Optum — processes half of all medical claims, according to a Department of Justice lawsuit. The American Hospital Association described the cyberattack as “the most significant and consequential incident of its kind” in US history.
By late March, UnitedHealth Group said nearly all medical and pharmacy claims were processing properly, while a deputy secretary of the US Department of Health & Human Services told clinicians that officials were focusing on the last group of clinicians who were facing cash-flow problems.
Still, a senior advisor with CMS told providers at that time that “we have heard from so many providers over the last several weeks who are really struggling to make ends meet right now or who are worried that they will not be able to make payroll in the weeks to come.”
Randy Dotinga is a freelance health/medical reporter and board member of the Association of Health Care Journalists.
A version of this article appeared on Medscape.com.
The Centers for Medicare & Medicaid Services (CMS) has announced the conclusion of a program that provided billions in early Medicare payments to those affected by the Change Healthcare/UnitedHealth Group cyberattack last winter.
CMS reported that the program advanced more than $2.55 billion in Medicare payments to > 4200 Part A providers, including hospitals, and more than $717.18 million in payments to Part B suppliers such as physicians, nonphysician practitioners, and durable medical equipment suppliers.
According to CMS, the Medicare billing system is now functioning properly, and 96% of the early payments have been recovered. The advances were to represent ≤ 30 days of typical claims payments in a 3-month period of 2023, with full repayment expected within 90 days through “automatic recoupment from Medicare claims” — no extensions allowed.
The agency took a victory lap regarding its response. “In the face of one of the most widespread cyberattacks on the US health care industry, CMS promptly took action to get providers and suppliers access to the funds they needed to continue providing patients with vital care,” CMS Administrator Chiquita Brooks-LaSure said in a statement. “Our efforts helped minimize the disruptive fallout from this incident, and we will remain vigilant to be ready to address future events.”
Ongoing Concerns from Health Care Organizations
Ben Teicher, an American Hospital Association spokesman, said that the organization hopes that CMS will be responsive if there’s more need for action after the advance payment program expires. The organization represents about 5000 hospitals, health care systems, and other providers.
“Our members report that the aftereffects of this event will likely be felt throughout the remainder of the year,” he said. According to Teicher, hospitals remain concerned about their ability to process claims and appeal denials, the safety of reconnecting to cyber services, and access to information needed to bill patients and reconcile payments.
In addition, hospitals are concerned about “financial support to mitigate the considerable costs incurred as a result of the cyberattack,” he said.
Charlene MacDonald, executive vice-president of public affairs at the Federation of American Hospitals, which represents more than 1000 for-profit hospitals, sent a statement to this news organization that said some providers “are still feeling the effects of care denials and delays caused by insurer inaction.
“We appreciate that the Administration acted within its authority to support providers during this unprecedented crisis and blunt these devastating impacts, especially because a vast majority of managed care companies failed to step up to the plate,” she said. “It is now time to shift our focus to holding plans accountable for using tactics to delay and deny needed patient care.”
Cyberattack Impact and Response
The ransom-based cyberattack against Change Healthcare/UnitedHealth Group targeted an electronic data interchange clearing house processing payer reimbursement systems, disrupting cash flows at hospitals and medical practices, and affecting patient access to prescriptions and life-saving therapy.
Change Healthcare — part of the UnitedHealth Group subsidiary Optum — processes half of all medical claims, according to a Department of Justice lawsuit. The American Hospital Association described the cyberattack as “the most significant and consequential incident of its kind” in US history.
By late March, UnitedHealth Group said nearly all medical and pharmacy claims were processing properly, while a deputy secretary of the US Department of Health & Human Services told clinicians that officials were focusing on the last group of clinicians who were facing cash-flow problems.
Still, a senior advisor with CMS told providers at that time that “we have heard from so many providers over the last several weeks who are really struggling to make ends meet right now or who are worried that they will not be able to make payroll in the weeks to come.”
Randy Dotinga is a freelance health/medical reporter and board member of the Association of Health Care Journalists.
A version of this article appeared on Medscape.com.
Beta Thalassemia: Pricey Gene Therapy Hits The Mark
With luck, maybe Ms. Ahmed’s son could follow in his aunt’s footsteps and get a stem cell transplant from a compatible family donor. But while little Yusuf Saeed has a twin sister of his own, she wasn’t a match. Without another treatment option, he’d face the prospect of a lifetime not only cut short but burdened by multiple monthly transfusions and severe limitations.
Then came glimpses of hope. One of Yusuf’s physicians at Cohen Children’s Medical Center in Long Island, New York, told Yusuf’s mother about a new kind of gene therapy on the horizon. But it took time to get FDA approval. Yusuf grew older, heading toward his teenage years, when regular transfusions would be a huge burden. “He’s turning 5 and 6, and there’s nothing,” Ms. Ahmed recalled, and the family worried.
Finally, the FDA approved the one-time treatment — betibeglogene autotemcel (beti-cel, Zynteglo) in 2022. By January 2024, the hospital was ready to treat Yusuf. At age 8, he became the first patient in the state of New York to undergo gene therapy for beta thalassemia.
A medical team infused Yusuf with his own stem cells, which had been genetically engineered to boost production of hemoglobin and prevent thalassemia’s devastating effects.
There are caveats about the treatment. It’s an extraordinarily expensive therapy that can be performed at only a few institutions. And it’s so brand new that caveats may not even have appeared yet. Yet, for kids like Yusuf, the gene therapy could transform a life.
“We feel like a weight has been lifted,” Ms. Ahmed said in an interview. “It’s something we’ve been waiting for.”
Anemia Becomes a Lifetime Threat
Among all genetic diseases, thalassemia stands alone. It’s the most common condition caused by a single gene, according to Hanny Al-Samkari, MD, a hematologist/clinical investigator at Massachusetts General Hospital and associate professor of medicine at Harvard Medical School, in Boston, Massachusetts.
Millions of people have the thalassemia trait, especially in southern Europe, the Middle East, southeast Asia, and Africa, Dr. Al-Samkari said. (Yusuf’s parents are from Pakistan.)
The trait, which appears to provide protection against malaria, may cause mild anemia in some cases but is otherwise harmless. However, a child born to parents with the same kind of trait has a high risk of developing alpha thalassemia or beta thalassemia. Like his aunt, Yusuf developed beta thalassemia, which is generally more severe. Yusuf’s bleeding disorder requires him to be transfusion-dependent.
In these patients, the disease disrupts the production of red blood cells in the bone marrow, Dr. Al-Samkari said. Hemoglobin levels can fall to 7 or 8 g/dL, compared with the normal levels of 12-16 g/dL in adults. “They’re chronically anemic, and that low hemoglobin that leads to things you associate with anemia: fatigue, reduced exercise tolerance, mind fog, challenges with work or school, and hypersomnolence.”
In addition, the bones become thinner and more brittle, he said, leading to fractures.
Transfusions are one treatment option, but they’re needed for a lifetime and cause their own problems, such as iron overload. Care of thalassemia patients “becomes quite complex and quite challenging for both families and medical institutions,” Alexis A. Thompson MD, MPH, chief of hematology at Children’s Hospital of Philadelphia, Pennsylvania, said in an interview.
Yusara Ahmed remembers her sister’s endless visits to the hospital after she was diagnosed at age 4. “We were all very traumatized by the hospital environment,” she said. But good news came in 2008, a few years later, when her sister was able to get a stem cell transplant from their brother.
But while stem cell transplants can be curative, most children don’t have a relative who can be a suitable match as a donor, Dr. Thompson said. Now, gene therapy offers another option, by turning a patient into his or her own matched donor.
Stem Cells Out, Stem Cells In
Last year, Yusuf went to Cohen Children’s Medical Center to donate stem cells, which were sent to a laboratory where they were genetically engineered to add copies of the beta-globin gene. Then, in January 2024, the modified stem cells were infused back into Yusuf after he underwent chemotherapy to make room for them in his bone marrow.
In April, a bald-headed Yusuf played with toy dinosaurs while his mother and clinicians met the media at a hospital press conference about his so-far-successful treatment. Early reports about the efficacy of the treatment suggest it may be the proverbial “game changer” for many of the estimated 100,000-plus people in the world who are diagnosed with transfusion-dependent beta thalassemia each year.
Over a median follow-up of 29.5 months, 20 of 22 patients treated with beti-cel no longer needed transfusions, according to a 2022 open-label phase 3 study published in the New England Journal of Medicine. Only one adverse event — thrombocytopenia in one patient — was considered both serious and related to the treatment, the industry-funded trial reported.
Costly Treatment Seems to Be Cost-Effective
As of 2022, gene therapy for transfusion-dependent beta thalassemia was listed as $2.8 million per treatment making it the most expensive single-treatment therapy ever approved in the United States. The price is “extraordinary,” said Dr. Thompson. “For some families, it gives them pause when they first hear about it.”
The hospital makes the case to insurers that covering the treatment is cost-effective in the long run, considering the high cost of traditional treatment, she said. “We’ve been very successful in getting coverage.”
In addition, the independent Institute for Clinical and Economic Review reported in 2022 that the treatment will be cost-effective at the “anticipated price of $2.1 million with an 80% payback option for patients who do not achieve and maintain transfusion independence over a 5-year period.”
Moving Forward, Clinicians Want to Reduce Complications
What’s next for transfusion-dependent beta thalassemia treatment? Earlier this year, the FDA approved a second gene therapy treatment called exagamglogene autotemcel (exa-cel, Casgevy). “We’re just beginning to evaluate individuals for the product, and we intend to make it available for families as well,” Dr. Thompson said.
In the bigger picture, she said gene therapy still has room for improvement. The need for chemotherapy is one target. According to her, it causes most of the complications related to gene therapy.
“Chemotherapy is a part of all gene therapies today because one has to make space in the bone marrow in order to have modified stem cells to come back to settle in and grow,” she said.
One strategy is to reduce the number of stem cells that are required for the therapy to work. “That would essentially eliminate the need for chemotherapy,” she said. “We’re not there yet.”
Another goal is to reduce the small risk of complications from gene therapy itself, she said. “Overall, though, this doesn’t detract us at all from being very excited about how well children are doing with the current approach. We’re very enthusiastic and very confident in recommending it to families.”
Back on Long Island, a Sense of Relief
Several months after his treatment, Yusuf is doing well. His hemoglobin levels are increasing, and his bone marrow has grown back, his mother said. He’s being home-schooled for the time being because he still faces a risk of infection. (Ms. Ahmed, a stay-at-home mom, has worked a teacher and mosque volunteer. Her husband runs a consumer electronics business.)
As Yusuf gets better, his parents hope they’ll soon be able to take a long trip back home to Pakistan to see relatives. They’ll be able to share their son with family along with something else: a sense of relief.
Dr. Al-Samkari discloses consulting for Agios. Dr. Thompson discloses research for Beam, Bluebird Bio, Editas, Novartis, and Novo Nordisk and consulting for Beam, Bluebird Bio, Editas, Roche, and Vertex.
With luck, maybe Ms. Ahmed’s son could follow in his aunt’s footsteps and get a stem cell transplant from a compatible family donor. But while little Yusuf Saeed has a twin sister of his own, she wasn’t a match. Without another treatment option, he’d face the prospect of a lifetime not only cut short but burdened by multiple monthly transfusions and severe limitations.
Then came glimpses of hope. One of Yusuf’s physicians at Cohen Children’s Medical Center in Long Island, New York, told Yusuf’s mother about a new kind of gene therapy on the horizon. But it took time to get FDA approval. Yusuf grew older, heading toward his teenage years, when regular transfusions would be a huge burden. “He’s turning 5 and 6, and there’s nothing,” Ms. Ahmed recalled, and the family worried.
Finally, the FDA approved the one-time treatment — betibeglogene autotemcel (beti-cel, Zynteglo) in 2022. By January 2024, the hospital was ready to treat Yusuf. At age 8, he became the first patient in the state of New York to undergo gene therapy for beta thalassemia.
A medical team infused Yusuf with his own stem cells, which had been genetically engineered to boost production of hemoglobin and prevent thalassemia’s devastating effects.
There are caveats about the treatment. It’s an extraordinarily expensive therapy that can be performed at only a few institutions. And it’s so brand new that caveats may not even have appeared yet. Yet, for kids like Yusuf, the gene therapy could transform a life.
“We feel like a weight has been lifted,” Ms. Ahmed said in an interview. “It’s something we’ve been waiting for.”
Anemia Becomes a Lifetime Threat
Among all genetic diseases, thalassemia stands alone. It’s the most common condition caused by a single gene, according to Hanny Al-Samkari, MD, a hematologist/clinical investigator at Massachusetts General Hospital and associate professor of medicine at Harvard Medical School, in Boston, Massachusetts.
Millions of people have the thalassemia trait, especially in southern Europe, the Middle East, southeast Asia, and Africa, Dr. Al-Samkari said. (Yusuf’s parents are from Pakistan.)
The trait, which appears to provide protection against malaria, may cause mild anemia in some cases but is otherwise harmless. However, a child born to parents with the same kind of trait has a high risk of developing alpha thalassemia or beta thalassemia. Like his aunt, Yusuf developed beta thalassemia, which is generally more severe. Yusuf’s bleeding disorder requires him to be transfusion-dependent.
In these patients, the disease disrupts the production of red blood cells in the bone marrow, Dr. Al-Samkari said. Hemoglobin levels can fall to 7 or 8 g/dL, compared with the normal levels of 12-16 g/dL in adults. “They’re chronically anemic, and that low hemoglobin that leads to things you associate with anemia: fatigue, reduced exercise tolerance, mind fog, challenges with work or school, and hypersomnolence.”
In addition, the bones become thinner and more brittle, he said, leading to fractures.
Transfusions are one treatment option, but they’re needed for a lifetime and cause their own problems, such as iron overload. Care of thalassemia patients “becomes quite complex and quite challenging for both families and medical institutions,” Alexis A. Thompson MD, MPH, chief of hematology at Children’s Hospital of Philadelphia, Pennsylvania, said in an interview.
Yusara Ahmed remembers her sister’s endless visits to the hospital after she was diagnosed at age 4. “We were all very traumatized by the hospital environment,” she said. But good news came in 2008, a few years later, when her sister was able to get a stem cell transplant from their brother.
But while stem cell transplants can be curative, most children don’t have a relative who can be a suitable match as a donor, Dr. Thompson said. Now, gene therapy offers another option, by turning a patient into his or her own matched donor.
Stem Cells Out, Stem Cells In
Last year, Yusuf went to Cohen Children’s Medical Center to donate stem cells, which were sent to a laboratory where they were genetically engineered to add copies of the beta-globin gene. Then, in January 2024, the modified stem cells were infused back into Yusuf after he underwent chemotherapy to make room for them in his bone marrow.
In April, a bald-headed Yusuf played with toy dinosaurs while his mother and clinicians met the media at a hospital press conference about his so-far-successful treatment. Early reports about the efficacy of the treatment suggest it may be the proverbial “game changer” for many of the estimated 100,000-plus people in the world who are diagnosed with transfusion-dependent beta thalassemia each year.
Over a median follow-up of 29.5 months, 20 of 22 patients treated with beti-cel no longer needed transfusions, according to a 2022 open-label phase 3 study published in the New England Journal of Medicine. Only one adverse event — thrombocytopenia in one patient — was considered both serious and related to the treatment, the industry-funded trial reported.
Costly Treatment Seems to Be Cost-Effective
As of 2022, gene therapy for transfusion-dependent beta thalassemia was listed as $2.8 million per treatment making it the most expensive single-treatment therapy ever approved in the United States. The price is “extraordinary,” said Dr. Thompson. “For some families, it gives them pause when they first hear about it.”
The hospital makes the case to insurers that covering the treatment is cost-effective in the long run, considering the high cost of traditional treatment, she said. “We’ve been very successful in getting coverage.”
In addition, the independent Institute for Clinical and Economic Review reported in 2022 that the treatment will be cost-effective at the “anticipated price of $2.1 million with an 80% payback option for patients who do not achieve and maintain transfusion independence over a 5-year period.”
Moving Forward, Clinicians Want to Reduce Complications
What’s next for transfusion-dependent beta thalassemia treatment? Earlier this year, the FDA approved a second gene therapy treatment called exagamglogene autotemcel (exa-cel, Casgevy). “We’re just beginning to evaluate individuals for the product, and we intend to make it available for families as well,” Dr. Thompson said.
In the bigger picture, she said gene therapy still has room for improvement. The need for chemotherapy is one target. According to her, it causes most of the complications related to gene therapy.
“Chemotherapy is a part of all gene therapies today because one has to make space in the bone marrow in order to have modified stem cells to come back to settle in and grow,” she said.
One strategy is to reduce the number of stem cells that are required for the therapy to work. “That would essentially eliminate the need for chemotherapy,” she said. “We’re not there yet.”
Another goal is to reduce the small risk of complications from gene therapy itself, she said. “Overall, though, this doesn’t detract us at all from being very excited about how well children are doing with the current approach. We’re very enthusiastic and very confident in recommending it to families.”
Back on Long Island, a Sense of Relief
Several months after his treatment, Yusuf is doing well. His hemoglobin levels are increasing, and his bone marrow has grown back, his mother said. He’s being home-schooled for the time being because he still faces a risk of infection. (Ms. Ahmed, a stay-at-home mom, has worked a teacher and mosque volunteer. Her husband runs a consumer electronics business.)
As Yusuf gets better, his parents hope they’ll soon be able to take a long trip back home to Pakistan to see relatives. They’ll be able to share their son with family along with something else: a sense of relief.
Dr. Al-Samkari discloses consulting for Agios. Dr. Thompson discloses research for Beam, Bluebird Bio, Editas, Novartis, and Novo Nordisk and consulting for Beam, Bluebird Bio, Editas, Roche, and Vertex.
With luck, maybe Ms. Ahmed’s son could follow in his aunt’s footsteps and get a stem cell transplant from a compatible family donor. But while little Yusuf Saeed has a twin sister of his own, she wasn’t a match. Without another treatment option, he’d face the prospect of a lifetime not only cut short but burdened by multiple monthly transfusions and severe limitations.
Then came glimpses of hope. One of Yusuf’s physicians at Cohen Children’s Medical Center in Long Island, New York, told Yusuf’s mother about a new kind of gene therapy on the horizon. But it took time to get FDA approval. Yusuf grew older, heading toward his teenage years, when regular transfusions would be a huge burden. “He’s turning 5 and 6, and there’s nothing,” Ms. Ahmed recalled, and the family worried.
Finally, the FDA approved the one-time treatment — betibeglogene autotemcel (beti-cel, Zynteglo) in 2022. By January 2024, the hospital was ready to treat Yusuf. At age 8, he became the first patient in the state of New York to undergo gene therapy for beta thalassemia.
A medical team infused Yusuf with his own stem cells, which had been genetically engineered to boost production of hemoglobin and prevent thalassemia’s devastating effects.
There are caveats about the treatment. It’s an extraordinarily expensive therapy that can be performed at only a few institutions. And it’s so brand new that caveats may not even have appeared yet. Yet, for kids like Yusuf, the gene therapy could transform a life.
“We feel like a weight has been lifted,” Ms. Ahmed said in an interview. “It’s something we’ve been waiting for.”
Anemia Becomes a Lifetime Threat
Among all genetic diseases, thalassemia stands alone. It’s the most common condition caused by a single gene, according to Hanny Al-Samkari, MD, a hematologist/clinical investigator at Massachusetts General Hospital and associate professor of medicine at Harvard Medical School, in Boston, Massachusetts.
Millions of people have the thalassemia trait, especially in southern Europe, the Middle East, southeast Asia, and Africa, Dr. Al-Samkari said. (Yusuf’s parents are from Pakistan.)
The trait, which appears to provide protection against malaria, may cause mild anemia in some cases but is otherwise harmless. However, a child born to parents with the same kind of trait has a high risk of developing alpha thalassemia or beta thalassemia. Like his aunt, Yusuf developed beta thalassemia, which is generally more severe. Yusuf’s bleeding disorder requires him to be transfusion-dependent.
In these patients, the disease disrupts the production of red blood cells in the bone marrow, Dr. Al-Samkari said. Hemoglobin levels can fall to 7 or 8 g/dL, compared with the normal levels of 12-16 g/dL in adults. “They’re chronically anemic, and that low hemoglobin that leads to things you associate with anemia: fatigue, reduced exercise tolerance, mind fog, challenges with work or school, and hypersomnolence.”
In addition, the bones become thinner and more brittle, he said, leading to fractures.
Transfusions are one treatment option, but they’re needed for a lifetime and cause their own problems, such as iron overload. Care of thalassemia patients “becomes quite complex and quite challenging for both families and medical institutions,” Alexis A. Thompson MD, MPH, chief of hematology at Children’s Hospital of Philadelphia, Pennsylvania, said in an interview.
Yusara Ahmed remembers her sister’s endless visits to the hospital after she was diagnosed at age 4. “We were all very traumatized by the hospital environment,” she said. But good news came in 2008, a few years later, when her sister was able to get a stem cell transplant from their brother.
But while stem cell transplants can be curative, most children don’t have a relative who can be a suitable match as a donor, Dr. Thompson said. Now, gene therapy offers another option, by turning a patient into his or her own matched donor.
Stem Cells Out, Stem Cells In
Last year, Yusuf went to Cohen Children’s Medical Center to donate stem cells, which were sent to a laboratory where they were genetically engineered to add copies of the beta-globin gene. Then, in January 2024, the modified stem cells were infused back into Yusuf after he underwent chemotherapy to make room for them in his bone marrow.
In April, a bald-headed Yusuf played with toy dinosaurs while his mother and clinicians met the media at a hospital press conference about his so-far-successful treatment. Early reports about the efficacy of the treatment suggest it may be the proverbial “game changer” for many of the estimated 100,000-plus people in the world who are diagnosed with transfusion-dependent beta thalassemia each year.
Over a median follow-up of 29.5 months, 20 of 22 patients treated with beti-cel no longer needed transfusions, according to a 2022 open-label phase 3 study published in the New England Journal of Medicine. Only one adverse event — thrombocytopenia in one patient — was considered both serious and related to the treatment, the industry-funded trial reported.
Costly Treatment Seems to Be Cost-Effective
As of 2022, gene therapy for transfusion-dependent beta thalassemia was listed as $2.8 million per treatment making it the most expensive single-treatment therapy ever approved in the United States. The price is “extraordinary,” said Dr. Thompson. “For some families, it gives them pause when they first hear about it.”
The hospital makes the case to insurers that covering the treatment is cost-effective in the long run, considering the high cost of traditional treatment, she said. “We’ve been very successful in getting coverage.”
In addition, the independent Institute for Clinical and Economic Review reported in 2022 that the treatment will be cost-effective at the “anticipated price of $2.1 million with an 80% payback option for patients who do not achieve and maintain transfusion independence over a 5-year period.”
Moving Forward, Clinicians Want to Reduce Complications
What’s next for transfusion-dependent beta thalassemia treatment? Earlier this year, the FDA approved a second gene therapy treatment called exagamglogene autotemcel (exa-cel, Casgevy). “We’re just beginning to evaluate individuals for the product, and we intend to make it available for families as well,” Dr. Thompson said.
In the bigger picture, she said gene therapy still has room for improvement. The need for chemotherapy is one target. According to her, it causes most of the complications related to gene therapy.
“Chemotherapy is a part of all gene therapies today because one has to make space in the bone marrow in order to have modified stem cells to come back to settle in and grow,” she said.
One strategy is to reduce the number of stem cells that are required for the therapy to work. “That would essentially eliminate the need for chemotherapy,” she said. “We’re not there yet.”
Another goal is to reduce the small risk of complications from gene therapy itself, she said. “Overall, though, this doesn’t detract us at all from being very excited about how well children are doing with the current approach. We’re very enthusiastic and very confident in recommending it to families.”
Back on Long Island, a Sense of Relief
Several months after his treatment, Yusuf is doing well. His hemoglobin levels are increasing, and his bone marrow has grown back, his mother said. He’s being home-schooled for the time being because he still faces a risk of infection. (Ms. Ahmed, a stay-at-home mom, has worked a teacher and mosque volunteer. Her husband runs a consumer electronics business.)
As Yusuf gets better, his parents hope they’ll soon be able to take a long trip back home to Pakistan to see relatives. They’ll be able to share their son with family along with something else: a sense of relief.
Dr. Al-Samkari discloses consulting for Agios. Dr. Thompson discloses research for Beam, Bluebird Bio, Editas, Novartis, and Novo Nordisk and consulting for Beam, Bluebird Bio, Editas, Roche, and Vertex.
Myeloma: VRd Plus Isatuximab Improves Outcomes
Patients who took isatuximab (Sarclisa) plus bortezomib, lenalidomide, and dexamethasone (VRd) reached higher estimated progression-free survival at a median 59.7 months vs. those who took VRd alone (63.2% vs. 45.2%, respectively, 98.5% CI, hazard ratio [HR] = 0.60, P < .001), reported Thierry Facon, MD, professor of hematology at Lille University Hospital, France, and colleagues at the annual meeting of the American Society of Clinical Oncology in Chicago. The study was simultaneously published in The New England Journal of Medicine.
“The significant progression-free benefit observed with Sarclisa with combination therapy compared to VRd is important and encouraging for patients with newly diagnosed multiple myeloma,” Dr. Facon said in an interview. The findings demonstrated the VRd-isatuximab’s potential as “a first-in-class combination to address gaps in care for newly diagnosed multiple myeloma transplant-ineligible patients,” he said.
According to Dr. Facon, more than 180,000 people worldwide are diagnosed with MM each year, he said, making it the second-most common hematologic malignancy.
“There is a need for new frontline therapeutic options for all MM patients,” he said. “Effective frontline therapy has the potential to modify the course of the disease, which is a key outcome for transplant-ineligible patients who often face high rates of attrition in later lines of therapy.”
For the industry-funded IMROZ study, researchers recruited patients aged 18-80 at 93 sites in 21 nations from 2017-2019. All were ineligible for transplant due to comorbidities or being aged 65 or older. Exclusions included Eastern Cooperative Oncology Group (ECOG) performance status scores of more than 2.
The subjects were randomly assigned in a 3-to-2 ratio to isatuximab-VRd (n = 265) or VRd alone (n = 181) and received four induction cycles (6 weeks per cycle) followed by 4-week cycles of continuous treatment until disease progression, unacceptable adverse event, or other criteria for discontinuation. If progression occurred, patients could be switched from the VRd-only group to the isatuximab-VRd group.
The median age in both the isatuximab-VRd and VRd groups was 72. The percentages of women were 46.0% and 48.1%, respectively, and 72.5% and 72.4%, respectively, were White. The next largest race/ethnic group was Asian (11.7% and 9.4%, respectively). Almost all had ECOG status of 0 or 1 (88.7% and 89.5%, respectively).
At study cut-off in September 2023, the percentages of subjects in the isatuximab-VRd and VRd groups who were still receiving treatment were 47.2% and 24.3%, respectively.
An intention-to-treat analysis found that the two groups had similar rates of overall response (91.3% for isatuximab-VRd vs. 92.3% for VRd), but the isatuximab-VRd group had higher complete or better response (74.7% vs. 64.1%, P = .01).
The percentage of patients who were minimal residual disease (MRD)-negative and had a complete response was also higher in the VRd-isatuximab group vs. the VRd group (55.5% vs. 40.9%, respectively, P = .003). A total of 26.0% of patients in the VRd-isatuximab group died vs. 32.6% in the VRd group; the estimated overall survival rates at 60 months were 72.3% and 66.3%, respectively, HR = 0.78, 99.97% CI).
As for adverse events, grade 5 events were more common in the VRd-isatuximab group (11.0% vs. 5.5%), as were deaths within the first 60 days of treatment (1.5% vs. 0.6%). “The difference was driven in part by different treatment exposures,” the researchers reported. Treatment-emergent events led to treatment discontinuation in 22.8% and 26.0% of patients, respectively.
“The safety and tolerability of Sarclisa observed was consistent with the established safety profile of Sarclisa and VRd with no new safety signals observed,” Dr. Facon said.
In an interview, Zandra Klippel, MD, global product head for multiple myeloma at Sanofi — the maker of isatuximab and funder of the study — said the Food and Drug Administration has accepted a priority review application for the investigational use of isatuximab in combination with VRd for the treatment of patients with transplant-ineligible, newly diagnosed MM.
“Our FDA approval date is expected on September 27, 2024,” Dr. Klippel said. “If all goes well, we anticipate launching as early as 2024 in the US and rolling out in other key countries starting in 2025 and continuing through 2026.”
Dr. Klippel added that isatuximab “continues to be evaluated in multiple ongoing phase 3 clinical trials in combination with current standard treatments across the MM treatment continuum.”
In an interview, Sagar Lonial, MD, chair and professor of hematology and medical oncology and chief medical officer at Winship Cancer Institute at Emory University in Atlanta, said the study is “important.”
However, Dr. Lonial, who is familiar with the findings but didn’t take part in the study, said it’s difficult to understand the impact of the treatment on frail patients. It appears that the combination treatment may be good for frail patients, he said, “but I need to better understand the magnitude of the benefit in that subset a little more.”
As for adverse events, he said “they are what would be expected for a trial like this.”
Pneumonia and COVID-19 infections were higher in the VRd-isatuximab group, he said, and “we know in general that vaccine responses are blocked by CD38 antibodies.” This can be managed, he said, via intravenous immunoglobulin support.
Manni Mohyuddin, MD, assistant professor at Huntsman Cancer Institute in Utah, said in an interview that the findings suggest that in older, fit patients, “you can get fairly good outcomes without use of transplant.”
In the United States, many more patients in the cohort would have been considered transplant-eligible, he said, and not eliminated from consideration for transplant due to age over 65. However, as patients age, “you get more diminishing returns for transplants,” said Dr. Mohyuddin, who is familiar with the study findings but didn’t take part in the research.
All the drugs in the new combination are FDA approved, he said, although the combination isn’t. “I suspect this will make it to our guidelines very soon and then be reimbursed by insurance companies and Medicare.”
The study was funded by Sanofi and an M.D. Anderson Cancer Center support grant. Dr. Facon has no disclosures. Other study authors report multiple ties relationships with various drug makers. Dr. Lonial disclosed ties with Takeda, Amgen, Novartis, BMS, GSK, AbbVie, Genentech, Pfizer, Regeneron, Janssen, AstraZeneca, and TG Therapeutics). Dr. Mohyuddin disclosed a relationship with Janssen.
Patients who took isatuximab (Sarclisa) plus bortezomib, lenalidomide, and dexamethasone (VRd) reached higher estimated progression-free survival at a median 59.7 months vs. those who took VRd alone (63.2% vs. 45.2%, respectively, 98.5% CI, hazard ratio [HR] = 0.60, P < .001), reported Thierry Facon, MD, professor of hematology at Lille University Hospital, France, and colleagues at the annual meeting of the American Society of Clinical Oncology in Chicago. The study was simultaneously published in The New England Journal of Medicine.
“The significant progression-free benefit observed with Sarclisa with combination therapy compared to VRd is important and encouraging for patients with newly diagnosed multiple myeloma,” Dr. Facon said in an interview. The findings demonstrated the VRd-isatuximab’s potential as “a first-in-class combination to address gaps in care for newly diagnosed multiple myeloma transplant-ineligible patients,” he said.
According to Dr. Facon, more than 180,000 people worldwide are diagnosed with MM each year, he said, making it the second-most common hematologic malignancy.
“There is a need for new frontline therapeutic options for all MM patients,” he said. “Effective frontline therapy has the potential to modify the course of the disease, which is a key outcome for transplant-ineligible patients who often face high rates of attrition in later lines of therapy.”
For the industry-funded IMROZ study, researchers recruited patients aged 18-80 at 93 sites in 21 nations from 2017-2019. All were ineligible for transplant due to comorbidities or being aged 65 or older. Exclusions included Eastern Cooperative Oncology Group (ECOG) performance status scores of more than 2.
The subjects were randomly assigned in a 3-to-2 ratio to isatuximab-VRd (n = 265) or VRd alone (n = 181) and received four induction cycles (6 weeks per cycle) followed by 4-week cycles of continuous treatment until disease progression, unacceptable adverse event, or other criteria for discontinuation. If progression occurred, patients could be switched from the VRd-only group to the isatuximab-VRd group.
The median age in both the isatuximab-VRd and VRd groups was 72. The percentages of women were 46.0% and 48.1%, respectively, and 72.5% and 72.4%, respectively, were White. The next largest race/ethnic group was Asian (11.7% and 9.4%, respectively). Almost all had ECOG status of 0 or 1 (88.7% and 89.5%, respectively).
At study cut-off in September 2023, the percentages of subjects in the isatuximab-VRd and VRd groups who were still receiving treatment were 47.2% and 24.3%, respectively.
An intention-to-treat analysis found that the two groups had similar rates of overall response (91.3% for isatuximab-VRd vs. 92.3% for VRd), but the isatuximab-VRd group had higher complete or better response (74.7% vs. 64.1%, P = .01).
The percentage of patients who were minimal residual disease (MRD)-negative and had a complete response was also higher in the VRd-isatuximab group vs. the VRd group (55.5% vs. 40.9%, respectively, P = .003). A total of 26.0% of patients in the VRd-isatuximab group died vs. 32.6% in the VRd group; the estimated overall survival rates at 60 months were 72.3% and 66.3%, respectively, HR = 0.78, 99.97% CI).
As for adverse events, grade 5 events were more common in the VRd-isatuximab group (11.0% vs. 5.5%), as were deaths within the first 60 days of treatment (1.5% vs. 0.6%). “The difference was driven in part by different treatment exposures,” the researchers reported. Treatment-emergent events led to treatment discontinuation in 22.8% and 26.0% of patients, respectively.
“The safety and tolerability of Sarclisa observed was consistent with the established safety profile of Sarclisa and VRd with no new safety signals observed,” Dr. Facon said.
In an interview, Zandra Klippel, MD, global product head for multiple myeloma at Sanofi — the maker of isatuximab and funder of the study — said the Food and Drug Administration has accepted a priority review application for the investigational use of isatuximab in combination with VRd for the treatment of patients with transplant-ineligible, newly diagnosed MM.
“Our FDA approval date is expected on September 27, 2024,” Dr. Klippel said. “If all goes well, we anticipate launching as early as 2024 in the US and rolling out in other key countries starting in 2025 and continuing through 2026.”
Dr. Klippel added that isatuximab “continues to be evaluated in multiple ongoing phase 3 clinical trials in combination with current standard treatments across the MM treatment continuum.”
In an interview, Sagar Lonial, MD, chair and professor of hematology and medical oncology and chief medical officer at Winship Cancer Institute at Emory University in Atlanta, said the study is “important.”
However, Dr. Lonial, who is familiar with the findings but didn’t take part in the study, said it’s difficult to understand the impact of the treatment on frail patients. It appears that the combination treatment may be good for frail patients, he said, “but I need to better understand the magnitude of the benefit in that subset a little more.”
As for adverse events, he said “they are what would be expected for a trial like this.”
Pneumonia and COVID-19 infections were higher in the VRd-isatuximab group, he said, and “we know in general that vaccine responses are blocked by CD38 antibodies.” This can be managed, he said, via intravenous immunoglobulin support.
Manni Mohyuddin, MD, assistant professor at Huntsman Cancer Institute in Utah, said in an interview that the findings suggest that in older, fit patients, “you can get fairly good outcomes without use of transplant.”
In the United States, many more patients in the cohort would have been considered transplant-eligible, he said, and not eliminated from consideration for transplant due to age over 65. However, as patients age, “you get more diminishing returns for transplants,” said Dr. Mohyuddin, who is familiar with the study findings but didn’t take part in the research.
All the drugs in the new combination are FDA approved, he said, although the combination isn’t. “I suspect this will make it to our guidelines very soon and then be reimbursed by insurance companies and Medicare.”
The study was funded by Sanofi and an M.D. Anderson Cancer Center support grant. Dr. Facon has no disclosures. Other study authors report multiple ties relationships with various drug makers. Dr. Lonial disclosed ties with Takeda, Amgen, Novartis, BMS, GSK, AbbVie, Genentech, Pfizer, Regeneron, Janssen, AstraZeneca, and TG Therapeutics). Dr. Mohyuddin disclosed a relationship with Janssen.
Patients who took isatuximab (Sarclisa) plus bortezomib, lenalidomide, and dexamethasone (VRd) reached higher estimated progression-free survival at a median 59.7 months vs. those who took VRd alone (63.2% vs. 45.2%, respectively, 98.5% CI, hazard ratio [HR] = 0.60, P < .001), reported Thierry Facon, MD, professor of hematology at Lille University Hospital, France, and colleagues at the annual meeting of the American Society of Clinical Oncology in Chicago. The study was simultaneously published in The New England Journal of Medicine.
“The significant progression-free benefit observed with Sarclisa with combination therapy compared to VRd is important and encouraging for patients with newly diagnosed multiple myeloma,” Dr. Facon said in an interview. The findings demonstrated the VRd-isatuximab’s potential as “a first-in-class combination to address gaps in care for newly diagnosed multiple myeloma transplant-ineligible patients,” he said.
According to Dr. Facon, more than 180,000 people worldwide are diagnosed with MM each year, he said, making it the second-most common hematologic malignancy.
“There is a need for new frontline therapeutic options for all MM patients,” he said. “Effective frontline therapy has the potential to modify the course of the disease, which is a key outcome for transplant-ineligible patients who often face high rates of attrition in later lines of therapy.”
For the industry-funded IMROZ study, researchers recruited patients aged 18-80 at 93 sites in 21 nations from 2017-2019. All were ineligible for transplant due to comorbidities or being aged 65 or older. Exclusions included Eastern Cooperative Oncology Group (ECOG) performance status scores of more than 2.
The subjects were randomly assigned in a 3-to-2 ratio to isatuximab-VRd (n = 265) or VRd alone (n = 181) and received four induction cycles (6 weeks per cycle) followed by 4-week cycles of continuous treatment until disease progression, unacceptable adverse event, or other criteria for discontinuation. If progression occurred, patients could be switched from the VRd-only group to the isatuximab-VRd group.
The median age in both the isatuximab-VRd and VRd groups was 72. The percentages of women were 46.0% and 48.1%, respectively, and 72.5% and 72.4%, respectively, were White. The next largest race/ethnic group was Asian (11.7% and 9.4%, respectively). Almost all had ECOG status of 0 or 1 (88.7% and 89.5%, respectively).
At study cut-off in September 2023, the percentages of subjects in the isatuximab-VRd and VRd groups who were still receiving treatment were 47.2% and 24.3%, respectively.
An intention-to-treat analysis found that the two groups had similar rates of overall response (91.3% for isatuximab-VRd vs. 92.3% for VRd), but the isatuximab-VRd group had higher complete or better response (74.7% vs. 64.1%, P = .01).
The percentage of patients who were minimal residual disease (MRD)-negative and had a complete response was also higher in the VRd-isatuximab group vs. the VRd group (55.5% vs. 40.9%, respectively, P = .003). A total of 26.0% of patients in the VRd-isatuximab group died vs. 32.6% in the VRd group; the estimated overall survival rates at 60 months were 72.3% and 66.3%, respectively, HR = 0.78, 99.97% CI).
As for adverse events, grade 5 events were more common in the VRd-isatuximab group (11.0% vs. 5.5%), as were deaths within the first 60 days of treatment (1.5% vs. 0.6%). “The difference was driven in part by different treatment exposures,” the researchers reported. Treatment-emergent events led to treatment discontinuation in 22.8% and 26.0% of patients, respectively.
“The safety and tolerability of Sarclisa observed was consistent with the established safety profile of Sarclisa and VRd with no new safety signals observed,” Dr. Facon said.
In an interview, Zandra Klippel, MD, global product head for multiple myeloma at Sanofi — the maker of isatuximab and funder of the study — said the Food and Drug Administration has accepted a priority review application for the investigational use of isatuximab in combination with VRd for the treatment of patients with transplant-ineligible, newly diagnosed MM.
“Our FDA approval date is expected on September 27, 2024,” Dr. Klippel said. “If all goes well, we anticipate launching as early as 2024 in the US and rolling out in other key countries starting in 2025 and continuing through 2026.”
Dr. Klippel added that isatuximab “continues to be evaluated in multiple ongoing phase 3 clinical trials in combination with current standard treatments across the MM treatment continuum.”
In an interview, Sagar Lonial, MD, chair and professor of hematology and medical oncology and chief medical officer at Winship Cancer Institute at Emory University in Atlanta, said the study is “important.”
However, Dr. Lonial, who is familiar with the findings but didn’t take part in the study, said it’s difficult to understand the impact of the treatment on frail patients. It appears that the combination treatment may be good for frail patients, he said, “but I need to better understand the magnitude of the benefit in that subset a little more.”
As for adverse events, he said “they are what would be expected for a trial like this.”
Pneumonia and COVID-19 infections were higher in the VRd-isatuximab group, he said, and “we know in general that vaccine responses are blocked by CD38 antibodies.” This can be managed, he said, via intravenous immunoglobulin support.
Manni Mohyuddin, MD, assistant professor at Huntsman Cancer Institute in Utah, said in an interview that the findings suggest that in older, fit patients, “you can get fairly good outcomes without use of transplant.”
In the United States, many more patients in the cohort would have been considered transplant-eligible, he said, and not eliminated from consideration for transplant due to age over 65. However, as patients age, “you get more diminishing returns for transplants,” said Dr. Mohyuddin, who is familiar with the study findings but didn’t take part in the research.
All the drugs in the new combination are FDA approved, he said, although the combination isn’t. “I suspect this will make it to our guidelines very soon and then be reimbursed by insurance companies and Medicare.”
The study was funded by Sanofi and an M.D. Anderson Cancer Center support grant. Dr. Facon has no disclosures. Other study authors report multiple ties relationships with various drug makers. Dr. Lonial disclosed ties with Takeda, Amgen, Novartis, BMS, GSK, AbbVie, Genentech, Pfizer, Regeneron, Janssen, AstraZeneca, and TG Therapeutics). Dr. Mohyuddin disclosed a relationship with Janssen.
FROM ASCO 2024
MCL: Dual Therapy ‘Promising’ in Patients With TP53 mutations
In first-line patients (n = 29) and relapsed/refractory patients (n = 45) with TP53 mutations, complete response rates were 55% and 58%, respectively, reported hematologist-oncologist Michael Wang, MD, of the University of Texas MD Anderson Cancer Center, and colleagues, at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago.
“These results are encouraging in light of the poor responses and shorter survival outcomes with standard chemotherapy,” Dr. Wang said in an ASCO presentation.
The current standard of care for relapsed/refractory MCL includes Bruton tyrosine kinase inhibitors for first relapse and CAR T-cell therapy (CAR-T) for second relapse in eligible patients or pirtobrutinib (Jaypirca) in patients ineligible for CAR T-cell therapy, Ohio State University Comprehensive Cancer Center hematology specialist Narendranath Epperla, MD, MS, said in an interview. Dr. Epperla is familiar with the new study findings but didn’t take part in the research.
Options for third relapse and beyond include clinical trial, rituximab [Rituxan] and lenalidomide [Revlimid], and bortezomib [Velcade],” Dr. Epperla said. “Venetoclax is not currently FDA-approved but can also be considered at third relapse.”
Better therapies are needed for a number of reasons, including poor outcomes in high-risk patients, such as those with TP53 mutations and those who progress following CAR T, Dr. Epperla said. Also, “as the novel agents are being moved into earlier lines of therapy, there remains an unmet need in those who progress on these agents with fewer options in the relapsed setting.”
At last December’s American Society of Hematology annual meeting, Dr. Wang and colleagues reported on the primary analysis results from the Sympatico study. Patients with relapsed/refractory MCL after 1-5 prior therapies were randomly assigned to receive 560 mg of ibrutinib once daily with either placebo (n = 133) or 400 mg daily of venetoclax after ramp-up (n = 134) for 2 years. Then subjects continued taking ibrutinib alone until their disease progressed or they reached unacceptable toxicity.
At a median follow-up of 51.2 months, median progression-free survival was longer in the ibrutinib-venetoclax group vs. ibrutinib alone (hazard ratio [HR] = 0.65, 95% CI, P = .0052).
The new analysis pools several cohorts of patients with TP53 mutations who all took the combination therapy: 5 from a safety run-in phase, 40 from the randomized phase, and 29 from a first-line cohort (median age at baseline = 67).
Median overall survival was not reached in the first-line group and 35.0 months in the relapsed/refractory group (total = 47.1 months). Median progress-free survival in the groups was 22.0 months and 20.9 months, respectively, and median duration of response was 20.5 months and 26.5 months, respectively.
With regard to the new findings, “it is good to see the responses with ibrutinib and venetoclax were deep and durable,” Dr. Epperla said. The combination treatment “provides a good alternative option for TP53-mutated MCL patients who are ineligible for CAR-T.”
Dr. Epperla added that the findings about the addition of ibrutinib could apply to newer-generation Bruton tyrosine kinase inhibitors that have relatively better safety profiles.
However, Dr. Epperla cautioned that the treatment needs to be weighed against the toxicity and cost of the regimen of ibrutinib and venetoclax for 2 years then single-agent ibrutinib until progression or unacceptable toxicity.
This news organization reported in 2023 that estimated net spending on ibrutinib per Medicare data increased by nearly half from 2014-2020, reaching $11,980 in 2020 vs. $7,787 for venetoclax.
Dr. Epperla also noted that “there are newer therapies that are emerging, such as T-cell-engaging bispecific antibodies, and they have shown promising results.”
In an interview, Brad S. Kahl, MD, a hematologist-oncologist at Washington University, St. Louis, said the improvement in outcomes are “modestly significant.”
Dr. Kahl, who is familiar with the study findings but didn’t take part in the research, said it is “worth adding the venetoclax, particularly in these biologically high risk patients with p53 mutations. Venetoclax is not FDA-approved, so insurance approval will need to be determined on a case-by-case basis. The combination is very expensive.”
Dr. Kahl agreed with Dr. Epperla that the findings could be extrapolated to other Bruton tyrosine kinase inhibitors.
The study was funded by Pharmacyclics, an AbbVie Company. Dr. Epperla disclosed relationships with BeiGene and Eli Lilly. Dr. Kahl reported ties with AstraZeneca, BeiGene, Abbvie, and Genentech.
In first-line patients (n = 29) and relapsed/refractory patients (n = 45) with TP53 mutations, complete response rates were 55% and 58%, respectively, reported hematologist-oncologist Michael Wang, MD, of the University of Texas MD Anderson Cancer Center, and colleagues, at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago.
“These results are encouraging in light of the poor responses and shorter survival outcomes with standard chemotherapy,” Dr. Wang said in an ASCO presentation.
The current standard of care for relapsed/refractory MCL includes Bruton tyrosine kinase inhibitors for first relapse and CAR T-cell therapy (CAR-T) for second relapse in eligible patients or pirtobrutinib (Jaypirca) in patients ineligible for CAR T-cell therapy, Ohio State University Comprehensive Cancer Center hematology specialist Narendranath Epperla, MD, MS, said in an interview. Dr. Epperla is familiar with the new study findings but didn’t take part in the research.
Options for third relapse and beyond include clinical trial, rituximab [Rituxan] and lenalidomide [Revlimid], and bortezomib [Velcade],” Dr. Epperla said. “Venetoclax is not currently FDA-approved but can also be considered at third relapse.”
Better therapies are needed for a number of reasons, including poor outcomes in high-risk patients, such as those with TP53 mutations and those who progress following CAR T, Dr. Epperla said. Also, “as the novel agents are being moved into earlier lines of therapy, there remains an unmet need in those who progress on these agents with fewer options in the relapsed setting.”
At last December’s American Society of Hematology annual meeting, Dr. Wang and colleagues reported on the primary analysis results from the Sympatico study. Patients with relapsed/refractory MCL after 1-5 prior therapies were randomly assigned to receive 560 mg of ibrutinib once daily with either placebo (n = 133) or 400 mg daily of venetoclax after ramp-up (n = 134) for 2 years. Then subjects continued taking ibrutinib alone until their disease progressed or they reached unacceptable toxicity.
At a median follow-up of 51.2 months, median progression-free survival was longer in the ibrutinib-venetoclax group vs. ibrutinib alone (hazard ratio [HR] = 0.65, 95% CI, P = .0052).
The new analysis pools several cohorts of patients with TP53 mutations who all took the combination therapy: 5 from a safety run-in phase, 40 from the randomized phase, and 29 from a first-line cohort (median age at baseline = 67).
Median overall survival was not reached in the first-line group and 35.0 months in the relapsed/refractory group (total = 47.1 months). Median progress-free survival in the groups was 22.0 months and 20.9 months, respectively, and median duration of response was 20.5 months and 26.5 months, respectively.
With regard to the new findings, “it is good to see the responses with ibrutinib and venetoclax were deep and durable,” Dr. Epperla said. The combination treatment “provides a good alternative option for TP53-mutated MCL patients who are ineligible for CAR-T.”
Dr. Epperla added that the findings about the addition of ibrutinib could apply to newer-generation Bruton tyrosine kinase inhibitors that have relatively better safety profiles.
However, Dr. Epperla cautioned that the treatment needs to be weighed against the toxicity and cost of the regimen of ibrutinib and venetoclax for 2 years then single-agent ibrutinib until progression or unacceptable toxicity.
This news organization reported in 2023 that estimated net spending on ibrutinib per Medicare data increased by nearly half from 2014-2020, reaching $11,980 in 2020 vs. $7,787 for venetoclax.
Dr. Epperla also noted that “there are newer therapies that are emerging, such as T-cell-engaging bispecific antibodies, and they have shown promising results.”
In an interview, Brad S. Kahl, MD, a hematologist-oncologist at Washington University, St. Louis, said the improvement in outcomes are “modestly significant.”
Dr. Kahl, who is familiar with the study findings but didn’t take part in the research, said it is “worth adding the venetoclax, particularly in these biologically high risk patients with p53 mutations. Venetoclax is not FDA-approved, so insurance approval will need to be determined on a case-by-case basis. The combination is very expensive.”
Dr. Kahl agreed with Dr. Epperla that the findings could be extrapolated to other Bruton tyrosine kinase inhibitors.
The study was funded by Pharmacyclics, an AbbVie Company. Dr. Epperla disclosed relationships with BeiGene and Eli Lilly. Dr. Kahl reported ties with AstraZeneca, BeiGene, Abbvie, and Genentech.
In first-line patients (n = 29) and relapsed/refractory patients (n = 45) with TP53 mutations, complete response rates were 55% and 58%, respectively, reported hematologist-oncologist Michael Wang, MD, of the University of Texas MD Anderson Cancer Center, and colleagues, at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago.
“These results are encouraging in light of the poor responses and shorter survival outcomes with standard chemotherapy,” Dr. Wang said in an ASCO presentation.
The current standard of care for relapsed/refractory MCL includes Bruton tyrosine kinase inhibitors for first relapse and CAR T-cell therapy (CAR-T) for second relapse in eligible patients or pirtobrutinib (Jaypirca) in patients ineligible for CAR T-cell therapy, Ohio State University Comprehensive Cancer Center hematology specialist Narendranath Epperla, MD, MS, said in an interview. Dr. Epperla is familiar with the new study findings but didn’t take part in the research.
Options for third relapse and beyond include clinical trial, rituximab [Rituxan] and lenalidomide [Revlimid], and bortezomib [Velcade],” Dr. Epperla said. “Venetoclax is not currently FDA-approved but can also be considered at third relapse.”
Better therapies are needed for a number of reasons, including poor outcomes in high-risk patients, such as those with TP53 mutations and those who progress following CAR T, Dr. Epperla said. Also, “as the novel agents are being moved into earlier lines of therapy, there remains an unmet need in those who progress on these agents with fewer options in the relapsed setting.”
At last December’s American Society of Hematology annual meeting, Dr. Wang and colleagues reported on the primary analysis results from the Sympatico study. Patients with relapsed/refractory MCL after 1-5 prior therapies were randomly assigned to receive 560 mg of ibrutinib once daily with either placebo (n = 133) or 400 mg daily of venetoclax after ramp-up (n = 134) for 2 years. Then subjects continued taking ibrutinib alone until their disease progressed or they reached unacceptable toxicity.
At a median follow-up of 51.2 months, median progression-free survival was longer in the ibrutinib-venetoclax group vs. ibrutinib alone (hazard ratio [HR] = 0.65, 95% CI, P = .0052).
The new analysis pools several cohorts of patients with TP53 mutations who all took the combination therapy: 5 from a safety run-in phase, 40 from the randomized phase, and 29 from a first-line cohort (median age at baseline = 67).
Median overall survival was not reached in the first-line group and 35.0 months in the relapsed/refractory group (total = 47.1 months). Median progress-free survival in the groups was 22.0 months and 20.9 months, respectively, and median duration of response was 20.5 months and 26.5 months, respectively.
With regard to the new findings, “it is good to see the responses with ibrutinib and venetoclax were deep and durable,” Dr. Epperla said. The combination treatment “provides a good alternative option for TP53-mutated MCL patients who are ineligible for CAR-T.”
Dr. Epperla added that the findings about the addition of ibrutinib could apply to newer-generation Bruton tyrosine kinase inhibitors that have relatively better safety profiles.
However, Dr. Epperla cautioned that the treatment needs to be weighed against the toxicity and cost of the regimen of ibrutinib and venetoclax for 2 years then single-agent ibrutinib until progression or unacceptable toxicity.
This news organization reported in 2023 that estimated net spending on ibrutinib per Medicare data increased by nearly half from 2014-2020, reaching $11,980 in 2020 vs. $7,787 for venetoclax.
Dr. Epperla also noted that “there are newer therapies that are emerging, such as T-cell-engaging bispecific antibodies, and they have shown promising results.”
In an interview, Brad S. Kahl, MD, a hematologist-oncologist at Washington University, St. Louis, said the improvement in outcomes are “modestly significant.”
Dr. Kahl, who is familiar with the study findings but didn’t take part in the research, said it is “worth adding the venetoclax, particularly in these biologically high risk patients with p53 mutations. Venetoclax is not FDA-approved, so insurance approval will need to be determined on a case-by-case basis. The combination is very expensive.”
Dr. Kahl agreed with Dr. Epperla that the findings could be extrapolated to other Bruton tyrosine kinase inhibitors.
The study was funded by Pharmacyclics, an AbbVie Company. Dr. Epperla disclosed relationships with BeiGene and Eli Lilly. Dr. Kahl reported ties with AstraZeneca, BeiGene, Abbvie, and Genentech.
FROM ASCO 2024