B Cell Lymphoma

CHICAGO – Fewer than 7% of patients newly diagnosed with cancer are tested for germline genetic mutations, and the percentage tested was even lower among racial and ethnic minorities, a huge study has found.

Information from germline genetic testing could affect a patient’s cancer care. For example, such testing could indicate that targeted therapies would be beneficial, and it would have implications for close relatives who may carry the same genes.

The finding that so few patients with newly diagnosed cancer were tested comes from an analysis of data on more than 1.3 million individuals across two U.S. states. The data were taken from the Surveillance, Epidemiology, and End Results (SEER) registry.

The rate is “well below guideline recommendations,” said study presenter Allison W. Kurian, MD, department of medicine, Stanford (Calif.) University.

“Innovative care delivery” is needed to tackle the problem, including the streamlining of pretest counseling, making posttest counseling more widely available, and employing long-term follow-up to track patient outcomes, she suggested.

“I do think this is a time for creative solutions of a number of different kinds,” she said. She suggested that lessons could be learned from the use of telemedicine during the COVID-19 pandemic. She also noted that “there have been some interesting studies on embedding genetic counselors in oncology clinics.”

Dr. Kurian presented the study at the annual meeting of the American Society of Clinical Oncology (ASCO). The study was simultaneously published in the Journal of the American Medical Association.

The current results represent a “missed opportunity for decrease the population-level burden of cancer,” experts noted in an accompanying editorial.

“Clinicians should recommend testing to their patients and provide them with the information necessary to make informed decisions about whether to undergo testing,” Zsofia K. Stadler, MD, and Deborah Schrag, MD, MPH, of Memorial Sloan Kettering Cancer Center, New York, wrote in their editorial.

They suggested novel approaches to widen access, such as use of point-of-care testing, telecounseling, and, in the future, chatbots to respond to patient questions.

“With greater emphasis on overcoming both health system and patient-level barriers to genetic cancer susceptibility testing for patients with cancer, treatment outcomes will improve and cancer diagnoses and related deaths in family members will be prevented,” they concluded.

At the meeting, invited discussant Erin Frances Cobain, MD, assistant professor of medical oncology, University of Michigan Health, Ann Arbor, referring to breast cancer as an example, said that progress has “stagnated” in recent years.

The study found a higher rate of gene testing among patients with newly diagnosed breast cancer, at just over 20%.

Dr. Cobain argued that this was still too low. She pointed out that “a recent study suggested that over 60% of individuals with an incident cancer diagnosis would meet criteria for genetic testing by National Comprehensive Cancer Network guidelines.

“This may be because testing is not offered, there may be poor access to genetic counseling resources, or patients may be offered testing but decline it,” she suggested.

One compelling reason to conduct genetic testing for patients newly diagnosed with breast cancer is that it may show that they are candidates for treatment with PARP (poly[ADP]-ribose polymerase) inhibitors, which “may have a direct impact on cancer-related mortality,” she pointed out.

“We need increased awareness and access to genetic testing resources for patients with breast cancer, particularly for racial and ethnic minorities,” she said.

Dr. Cobain also noted that finding variants of uncertain significance (VUS) was more likely among patients from racial and ethnic minorities than among White patients. She said such a finding “increases patient and physician anxiety,” and there may be “unclear optimal management recommendations for these patients.”
 

Details of the study

Germline genetic testing is “increasingly essential for cancer care,” Dr. Kurian said.

It is central to risk-adapted screening and secondary prevention, the use of targeted therapies, including PARP and checkpoint inhibitors, and cascade testing to identify at-risk relatives.

She pointed out that in clinical practice, testing has “evolved rapidly.” Panels include more and more genes. In addition, the cost of these tests is falling, and guidelines have become “more expansive.”

However, “little is known about genetic testing use and results,” Dr. Kurian noted.

The team therefore undertook the SEER-GeneLINK initiative, which involved patients aged ≥ 20 years who were diagnosed with cancer between Jan. 1, 2013, and March 31, 2019, and who were reported to statewide SEER registries in California and Georgia.

The team looked for patients for whom germline genetic test results had been reported by the four laboratories that performed the majority of patient testing in the two states. Results were categorized as pathogenic, benign, or VUS.

The results were classified on the basis of current guidelines for testing and/or management as related to breast/ovarian cancer, gastrointestinal cancer, other hereditary cancers, or those with no guidelines for testing or management.

Dr. Kurian reported that from an overall population of 1,412,388 patients diagnosed with cancer, 1,369,660 were eligible for inclusion. Of those, about half (51.9%) were women, and the majority (86.3%) were aged 50 years or older.

Many of these patients (61.4%) were non-Hispanic White persons, and slightly fewer than half (49.8%) were deemed to be in medium or high poverty, as determined using U.S. Census tract levels.

Overall, germline genetic testing was performed in 93,052 (6.8%) of patients over the study period.

Women were more likely to have undergone germline mutation testing than men, at 13.9% vs. 2.2%, as were patients aged 20-49 years, at 22.1% vs. 8.2% for those aged 50-69 years, and 3.3% for those aged 70 years and older.

The number of genes for which testing was conducted increased from a median of 2 in 2013 to 34 in 2019. Rates of VUS increased more than that for pathologic variants and substantially more so in non-White patients.

By 2019, the ratio of VUS to pathologic variants stood at 1.7 among White patients, vs. 3.9 among Asian patients, 3.6 among Black patients, and 2.2 among Hispanic patients.

The majority of identified pathologic variants that were related to the diagnosed cancer and genes with testing and/or management guidelines accounted for 67.5% to 94.9% of such variants.

Regarding specific cancer diagnoses, Dr. Kurian said that over the course of the study period, testing rates consistently exceeded 50% only among male breast cancer patients.

There were rapid increases in testing for ovarian cancer, from 28.0% of cases in 2013 to 54.0% in 2019. For pancreatic cancer, rates increased from 1.0% to 19.0% over the same period, and for prostate cancer, rates increased from 0.1% to 4.0%. She suggested that these increases in rates may be related to the approval of PARP inhibitors for use in these indications.

However, there was little change in the rates of germline mutation testing for lung cancer patients, from 01% in 2013 to 0.8% in 2019, and for other cancers, from 0.3% to 2.0%.

The results also revealed racial and ethnic differences in testing after controlling for age, cancer type, and year. Over the course of the study period, 8.0% of White patients underwent genetic testing, compared with 6.0% each for Asian, Black, and Hispanic patients and 5.0% for other patients (P < .001).

With regard specifically to male and female breast cancer and ovarian cancer, testing rates were 31% among White patients, 22% for Asian patients, 25% for Black patients, and 23% for Hispanic patients (P < .001).

Dr. Kurian acknowledged that the study is limited by a lack of testing from other laboratories and direct-to-consumer test data, although a recent survey suggested that this represents fewer than 5% of all germline genetic tests.

She also noted that the SEER registries do not collect data on family history or tumor sequencing.

The study was funded by the National Institutes of Health, and the Centers for Disease Control and Prevention. Dr. Kurian has relationships with Adela, Ambry Genetics, Color Genomics, GeneDx/BioReference, Genentech, InVitae, and Myriad Genetics. Other authors report numerous relationships with industry. Dr. Cobain has ties with AstraZeneca, Daiichi Sankyo, Athenex, Ayala Pharmaceuticals, bioTheranostics, and Immunomedics. Dr. Schrag has relationships with Merck, JAMA, AACR, and Grail. Dr. Stadler has ties with Adverum Biotechnologies, Genentech, Neurogene, Novartis, Optos Plc, Outlook Therapeutics, and Regeneron Pharmaceuticals.

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

CHICAGO – Fewer than 7% of patients newly diagnosed with cancer are tested for germline genetic mutations, and the percentage tested was even lower among racial and ethnic minorities, a huge study has found.

Information from germline genetic testing could affect a patient’s cancer care. For example, such testing could indicate that targeted therapies would be beneficial, and it would have implications for close relatives who may carry the same genes.

The finding that so few patients with newly diagnosed cancer were tested comes from an analysis of data on more than 1.3 million individuals across two U.S. states. The data were taken from the Surveillance, Epidemiology, and End Results (SEER) registry.

The rate is “well below guideline recommendations,” said study presenter Allison W. Kurian, MD, department of medicine, Stanford (Calif.) University.

“Innovative care delivery” is needed to tackle the problem, including the streamlining of pretest counseling, making posttest counseling more widely available, and employing long-term follow-up to track patient outcomes, she suggested.

“I do think this is a time for creative solutions of a number of different kinds,” she said. She suggested that lessons could be learned from the use of telemedicine during the COVID-19 pandemic. She also noted that “there have been some interesting studies on embedding genetic counselors in oncology clinics.”

Dr. Kurian presented the study at the annual meeting of the American Society of Clinical Oncology (ASCO). The study was simultaneously published in the Journal of the American Medical Association.

The current results represent a “missed opportunity for decrease the population-level burden of cancer,” experts noted in an accompanying editorial.

“Clinicians should recommend testing to their patients and provide them with the information necessary to make informed decisions about whether to undergo testing,” Zsofia K. Stadler, MD, and Deborah Schrag, MD, MPH, of Memorial Sloan Kettering Cancer Center, New York, wrote in their editorial.

They suggested novel approaches to widen access, such as use of point-of-care testing, telecounseling, and, in the future, chatbots to respond to patient questions.

“With greater emphasis on overcoming both health system and patient-level barriers to genetic cancer susceptibility testing for patients with cancer, treatment outcomes will improve and cancer diagnoses and related deaths in family members will be prevented,” they concluded.

At the meeting, invited discussant Erin Frances Cobain, MD, assistant professor of medical oncology, University of Michigan Health, Ann Arbor, referring to breast cancer as an example, said that progress has “stagnated” in recent years.

The study found a higher rate of gene testing among patients with newly diagnosed breast cancer, at just over 20%.

Dr. Cobain argued that this was still too low. She pointed out that “a recent study suggested that over 60% of individuals with an incident cancer diagnosis would meet criteria for genetic testing by National Comprehensive Cancer Network guidelines.

“This may be because testing is not offered, there may be poor access to genetic counseling resources, or patients may be offered testing but decline it,” she suggested.

One compelling reason to conduct genetic testing for patients newly diagnosed with breast cancer is that it may show that they are candidates for treatment with PARP (poly[ADP]-ribose polymerase) inhibitors, which “may have a direct impact on cancer-related mortality,” she pointed out.

“We need increased awareness and access to genetic testing resources for patients with breast cancer, particularly for racial and ethnic minorities,” she said.

Dr. Cobain also noted that finding variants of uncertain significance (VUS) was more likely among patients from racial and ethnic minorities than among White patients. She said such a finding “increases patient and physician anxiety,” and there may be “unclear optimal management recommendations for these patients.”
 

Details of the study

Germline genetic testing is “increasingly essential for cancer care,” Dr. Kurian said.

It is central to risk-adapted screening and secondary prevention, the use of targeted therapies, including PARP and checkpoint inhibitors, and cascade testing to identify at-risk relatives.

She pointed out that in clinical practice, testing has “evolved rapidly.” Panels include more and more genes. In addition, the cost of these tests is falling, and guidelines have become “more expansive.”

However, “little is known about genetic testing use and results,” Dr. Kurian noted.

The team therefore undertook the SEER-GeneLINK initiative, which involved patients aged ≥ 20 years who were diagnosed with cancer between Jan. 1, 2013, and March 31, 2019, and who were reported to statewide SEER registries in California and Georgia.

The team looked for patients for whom germline genetic test results had been reported by the four laboratories that performed the majority of patient testing in the two states. Results were categorized as pathogenic, benign, or VUS.

The results were classified on the basis of current guidelines for testing and/or management as related to breast/ovarian cancer, gastrointestinal cancer, other hereditary cancers, or those with no guidelines for testing or management.

Dr. Kurian reported that from an overall population of 1,412,388 patients diagnosed with cancer, 1,369,660 were eligible for inclusion. Of those, about half (51.9%) were women, and the majority (86.3%) were aged 50 years or older.

Many of these patients (61.4%) were non-Hispanic White persons, and slightly fewer than half (49.8%) were deemed to be in medium or high poverty, as determined using U.S. Census tract levels.

Overall, germline genetic testing was performed in 93,052 (6.8%) of patients over the study period.

Women were more likely to have undergone germline mutation testing than men, at 13.9% vs. 2.2%, as were patients aged 20-49 years, at 22.1% vs. 8.2% for those aged 50-69 years, and 3.3% for those aged 70 years and older.

The number of genes for which testing was conducted increased from a median of 2 in 2013 to 34 in 2019. Rates of VUS increased more than that for pathologic variants and substantially more so in non-White patients.

By 2019, the ratio of VUS to pathologic variants stood at 1.7 among White patients, vs. 3.9 among Asian patients, 3.6 among Black patients, and 2.2 among Hispanic patients.

The majority of identified pathologic variants that were related to the diagnosed cancer and genes with testing and/or management guidelines accounted for 67.5% to 94.9% of such variants.

Regarding specific cancer diagnoses, Dr. Kurian said that over the course of the study period, testing rates consistently exceeded 50% only among male breast cancer patients.

There were rapid increases in testing for ovarian cancer, from 28.0% of cases in 2013 to 54.0% in 2019. For pancreatic cancer, rates increased from 1.0% to 19.0% over the same period, and for prostate cancer, rates increased from 0.1% to 4.0%. She suggested that these increases in rates may be related to the approval of PARP inhibitors for use in these indications.

However, there was little change in the rates of germline mutation testing for lung cancer patients, from 01% in 2013 to 0.8% in 2019, and for other cancers, from 0.3% to 2.0%.

The results also revealed racial and ethnic differences in testing after controlling for age, cancer type, and year. Over the course of the study period, 8.0% of White patients underwent genetic testing, compared with 6.0% each for Asian, Black, and Hispanic patients and 5.0% for other patients (P < .001).

With regard specifically to male and female breast cancer and ovarian cancer, testing rates were 31% among White patients, 22% for Asian patients, 25% for Black patients, and 23% for Hispanic patients (P < .001).

Dr. Kurian acknowledged that the study is limited by a lack of testing from other laboratories and direct-to-consumer test data, although a recent survey suggested that this represents fewer than 5% of all germline genetic tests.

She also noted that the SEER registries do not collect data on family history or tumor sequencing.

The study was funded by the National Institutes of Health, and the Centers for Disease Control and Prevention. Dr. Kurian has relationships with Adela, Ambry Genetics, Color Genomics, GeneDx/BioReference, Genentech, InVitae, and Myriad Genetics. Other authors report numerous relationships with industry. Dr. Cobain has ties with AstraZeneca, Daiichi Sankyo, Athenex, Ayala Pharmaceuticals, bioTheranostics, and Immunomedics. Dr. Schrag has relationships with Merck, JAMA, AACR, and Grail. Dr. Stadler has ties with Adverum Biotechnologies, Genentech, Neurogene, Novartis, Optos Plc, Outlook Therapeutics, and Regeneron Pharmaceuticals.

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

CHICAGO – Fewer than 7% of patients newly diagnosed with cancer are tested for germline genetic mutations, and the percentage tested was even lower among racial and ethnic minorities, a huge study has found.

Information from germline genetic testing could affect a patient’s cancer care. For example, such testing could indicate that targeted therapies would be beneficial, and it would have implications for close relatives who may carry the same genes.

The finding that so few patients with newly diagnosed cancer were tested comes from an analysis of data on more than 1.3 million individuals across two U.S. states. The data were taken from the Surveillance, Epidemiology, and End Results (SEER) registry.

The rate is “well below guideline recommendations,” said study presenter Allison W. Kurian, MD, department of medicine, Stanford (Calif.) University.

“Innovative care delivery” is needed to tackle the problem, including the streamlining of pretest counseling, making posttest counseling more widely available, and employing long-term follow-up to track patient outcomes, she suggested.

“I do think this is a time for creative solutions of a number of different kinds,” she said. She suggested that lessons could be learned from the use of telemedicine during the COVID-19 pandemic. She also noted that “there have been some interesting studies on embedding genetic counselors in oncology clinics.”

Dr. Kurian presented the study at the annual meeting of the American Society of Clinical Oncology (ASCO). The study was simultaneously published in the Journal of the American Medical Association.

The current results represent a “missed opportunity for decrease the population-level burden of cancer,” experts noted in an accompanying editorial.

“Clinicians should recommend testing to their patients and provide them with the information necessary to make informed decisions about whether to undergo testing,” Zsofia K. Stadler, MD, and Deborah Schrag, MD, MPH, of Memorial Sloan Kettering Cancer Center, New York, wrote in their editorial.

They suggested novel approaches to widen access, such as use of point-of-care testing, telecounseling, and, in the future, chatbots to respond to patient questions.

“With greater emphasis on overcoming both health system and patient-level barriers to genetic cancer susceptibility testing for patients with cancer, treatment outcomes will improve and cancer diagnoses and related deaths in family members will be prevented,” they concluded.

At the meeting, invited discussant Erin Frances Cobain, MD, assistant professor of medical oncology, University of Michigan Health, Ann Arbor, referring to breast cancer as an example, said that progress has “stagnated” in recent years.

The study found a higher rate of gene testing among patients with newly diagnosed breast cancer, at just over 20%.

Dr. Cobain argued that this was still too low. She pointed out that “a recent study suggested that over 60% of individuals with an incident cancer diagnosis would meet criteria for genetic testing by National Comprehensive Cancer Network guidelines.

“This may be because testing is not offered, there may be poor access to genetic counseling resources, or patients may be offered testing but decline it,” she suggested.

One compelling reason to conduct genetic testing for patients newly diagnosed with breast cancer is that it may show that they are candidates for treatment with PARP (poly[ADP]-ribose polymerase) inhibitors, which “may have a direct impact on cancer-related mortality,” she pointed out.

“We need increased awareness and access to genetic testing resources for patients with breast cancer, particularly for racial and ethnic minorities,” she said.

Dr. Cobain also noted that finding variants of uncertain significance (VUS) was more likely among patients from racial and ethnic minorities than among White patients. She said such a finding “increases patient and physician anxiety,” and there may be “unclear optimal management recommendations for these patients.”
 

Details of the study

Germline genetic testing is “increasingly essential for cancer care,” Dr. Kurian said.

It is central to risk-adapted screening and secondary prevention, the use of targeted therapies, including PARP and checkpoint inhibitors, and cascade testing to identify at-risk relatives.

She pointed out that in clinical practice, testing has “evolved rapidly.” Panels include more and more genes. In addition, the cost of these tests is falling, and guidelines have become “more expansive.”

However, “little is known about genetic testing use and results,” Dr. Kurian noted.

The team therefore undertook the SEER-GeneLINK initiative, which involved patients aged ≥ 20 years who were diagnosed with cancer between Jan. 1, 2013, and March 31, 2019, and who were reported to statewide SEER registries in California and Georgia.

The team looked for patients for whom germline genetic test results had been reported by the four laboratories that performed the majority of patient testing in the two states. Results were categorized as pathogenic, benign, or VUS.

The results were classified on the basis of current guidelines for testing and/or management as related to breast/ovarian cancer, gastrointestinal cancer, other hereditary cancers, or those with no guidelines for testing or management.

Dr. Kurian reported that from an overall population of 1,412,388 patients diagnosed with cancer, 1,369,660 were eligible for inclusion. Of those, about half (51.9%) were women, and the majority (86.3%) were aged 50 years or older.

Many of these patients (61.4%) were non-Hispanic White persons, and slightly fewer than half (49.8%) were deemed to be in medium or high poverty, as determined using U.S. Census tract levels.

Overall, germline genetic testing was performed in 93,052 (6.8%) of patients over the study period.

Women were more likely to have undergone germline mutation testing than men, at 13.9% vs. 2.2%, as were patients aged 20-49 years, at 22.1% vs. 8.2% for those aged 50-69 years, and 3.3% for those aged 70 years and older.

The number of genes for which testing was conducted increased from a median of 2 in 2013 to 34 in 2019. Rates of VUS increased more than that for pathologic variants and substantially more so in non-White patients.

By 2019, the ratio of VUS to pathologic variants stood at 1.7 among White patients, vs. 3.9 among Asian patients, 3.6 among Black patients, and 2.2 among Hispanic patients.

The majority of identified pathologic variants that were related to the diagnosed cancer and genes with testing and/or management guidelines accounted for 67.5% to 94.9% of such variants.

Regarding specific cancer diagnoses, Dr. Kurian said that over the course of the study period, testing rates consistently exceeded 50% only among male breast cancer patients.

There were rapid increases in testing for ovarian cancer, from 28.0% of cases in 2013 to 54.0% in 2019. For pancreatic cancer, rates increased from 1.0% to 19.0% over the same period, and for prostate cancer, rates increased from 0.1% to 4.0%. She suggested that these increases in rates may be related to the approval of PARP inhibitors for use in these indications.

However, there was little change in the rates of germline mutation testing for lung cancer patients, from 01% in 2013 to 0.8% in 2019, and for other cancers, from 0.3% to 2.0%.

The results also revealed racial and ethnic differences in testing after controlling for age, cancer type, and year. Over the course of the study period, 8.0% of White patients underwent genetic testing, compared with 6.0% each for Asian, Black, and Hispanic patients and 5.0% for other patients (P < .001).

With regard specifically to male and female breast cancer and ovarian cancer, testing rates were 31% among White patients, 22% for Asian patients, 25% for Black patients, and 23% for Hispanic patients (P < .001).

Dr. Kurian acknowledged that the study is limited by a lack of testing from other laboratories and direct-to-consumer test data, although a recent survey suggested that this represents fewer than 5% of all germline genetic tests.

She also noted that the SEER registries do not collect data on family history or tumor sequencing.

The study was funded by the National Institutes of Health, and the Centers for Disease Control and Prevention. Dr. Kurian has relationships with Adela, Ambry Genetics, Color Genomics, GeneDx/BioReference, Genentech, InVitae, and Myriad Genetics. Other authors report numerous relationships with industry. Dr. Cobain has ties with AstraZeneca, Daiichi Sankyo, Athenex, Ayala Pharmaceuticals, bioTheranostics, and Immunomedics. Dr. Schrag has relationships with Merck, JAMA, AACR, and Grail. Dr. Stadler has ties with Adverum Biotechnologies, Genentech, Neurogene, Novartis, Optos Plc, Outlook Therapeutics, and Regeneron Pharmaceuticals.

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

Oncology fellows who completed diversity, equity, and inclusion (DEI) training report that they feel more confident about responding to different types of discrimination, both when directed at them personally and when directed at others.

The finding comes from a survey conducted after the introduction of DEI training within the Yale Medical Oncology-Hematology Fellowship Program. The study was reported by Norin Ansari, MD, MPH, of Yale Cancer Center, New Haven, Conn., at the annual meeting of the American Society of Clinical Oncology (ASCO).

Dr. Ansari emphasized the DEI curriculum in fellowship programs by highlighting the racial and gender disparities that exist among physicians.

“There is a significant representation problem – only 2%-3% of practicing oncologists are Black or Hispanic/Latino,” she said. “And that representation decreases with each stage in the pipeline of the workforce.”

Dr. Ansari also noted gender disparities in the oncologist workforce, reporting that about one-third of faculty positions are held by women.

The anonymous survey was sent to 29 fellows; 23 responded, including 8 first-year fellows and 13 senior fellows. Over 57% of respondents rated the importance of DEI education as 10 on a 10-point scale (mean, 8.6).

At the start of this year, the responses of senior fellows who had already received some DEI training during the previous year’s lecture series were compared with first-year fellows who had not had any fellowship DEI education.

First-year fellows reported a mean confidence score of 2.5/5 at navigating bias and microaggressions when experienced personally and a mean score of 2.9/5 when they were directed at others. Senior fellows reported mean confidence scores of 3 and 3.2, respectively.

Yale then compared longitudinal data on fellows’ comfort levels in navigating discrimination in 2021, 2022, and 2023 a month before the ASCO meeting.

Fellows were asked to rate their comfort level from 1 to 10 in navigating different types of discrimination, including racial inequality, sexual harassment, and gender discrimination. In these three categories, fellows rated comfortability as a 5 in 2021 and as 7 in 2023 after the DEI training.

“Our first goal is to normalize talking about DEI and to recognize that different people in our workforce have different experiences and how we can be allies for them and for our patients,” Dr. Ansari said. “And I think for long-term goals we want to take stock of who’s at the table, who’s making decisions, and how does that affect our field, our science, and our patients.”

Yale designed the 3-year longitudinal curriculum with two annual core topics: upstander training and journal club for discussion and reflection. An additional two to three training sessions per year will focus on either race, gender, LGBTQ+, disability, religion, or implicit bias training.

The most popular topics among fellows were upstander training, cancer treatment and outcomes disparities, recruitment and retention, and career promotion and pay disparities.

The preferred platforms of content delivery were lectures from experts in the field, affinity groups or mentorship links, small group discussions, and advocacy education.

Gerald Hsu, MD, PhD, with the San Francisco VA Medical Center, discussed the results of Yale’s DEI curriculum assessment, saying it represented “best practices” in the industry. However, he acknowledged that realistically, not everyone will be receptive to DEI training.

Dr. Hsu said that holding medical staff accountable is the only way to truly incorporate DEI into everyday practice.

“Collectively, we need to be holding ourselves to different standards or holding ourselves to some standard,” Dr. Hsu said. “Maybe we need to be setting goals to the degree to which we diversify our training programs and our faculty, and there needs to be consequences to not doing so.”

No funding for the study was reported.

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

Oncology fellows who completed diversity, equity, and inclusion (DEI) training report that they feel more confident about responding to different types of discrimination, both when directed at them personally and when directed at others.

The finding comes from a survey conducted after the introduction of DEI training within the Yale Medical Oncology-Hematology Fellowship Program. The study was reported by Norin Ansari, MD, MPH, of Yale Cancer Center, New Haven, Conn., at the annual meeting of the American Society of Clinical Oncology (ASCO).

Dr. Ansari emphasized the DEI curriculum in fellowship programs by highlighting the racial and gender disparities that exist among physicians.

“There is a significant representation problem – only 2%-3% of practicing oncologists are Black or Hispanic/Latino,” she said. “And that representation decreases with each stage in the pipeline of the workforce.”

Dr. Ansari also noted gender disparities in the oncologist workforce, reporting that about one-third of faculty positions are held by women.

The anonymous survey was sent to 29 fellows; 23 responded, including 8 first-year fellows and 13 senior fellows. Over 57% of respondents rated the importance of DEI education as 10 on a 10-point scale (mean, 8.6).

At the start of this year, the responses of senior fellows who had already received some DEI training during the previous year’s lecture series were compared with first-year fellows who had not had any fellowship DEI education.

First-year fellows reported a mean confidence score of 2.5/5 at navigating bias and microaggressions when experienced personally and a mean score of 2.9/5 when they were directed at others. Senior fellows reported mean confidence scores of 3 and 3.2, respectively.

Yale then compared longitudinal data on fellows’ comfort levels in navigating discrimination in 2021, 2022, and 2023 a month before the ASCO meeting.

Fellows were asked to rate their comfort level from 1 to 10 in navigating different types of discrimination, including racial inequality, sexual harassment, and gender discrimination. In these three categories, fellows rated comfortability as a 5 in 2021 and as 7 in 2023 after the DEI training.

“Our first goal is to normalize talking about DEI and to recognize that different people in our workforce have different experiences and how we can be allies for them and for our patients,” Dr. Ansari said. “And I think for long-term goals we want to take stock of who’s at the table, who’s making decisions, and how does that affect our field, our science, and our patients.”

Yale designed the 3-year longitudinal curriculum with two annual core topics: upstander training and journal club for discussion and reflection. An additional two to three training sessions per year will focus on either race, gender, LGBTQ+, disability, religion, or implicit bias training.

The most popular topics among fellows were upstander training, cancer treatment and outcomes disparities, recruitment and retention, and career promotion and pay disparities.

The preferred platforms of content delivery were lectures from experts in the field, affinity groups or mentorship links, small group discussions, and advocacy education.

Gerald Hsu, MD, PhD, with the San Francisco VA Medical Center, discussed the results of Yale’s DEI curriculum assessment, saying it represented “best practices” in the industry. However, he acknowledged that realistically, not everyone will be receptive to DEI training.

Dr. Hsu said that holding medical staff accountable is the only way to truly incorporate DEI into everyday practice.

“Collectively, we need to be holding ourselves to different standards or holding ourselves to some standard,” Dr. Hsu said. “Maybe we need to be setting goals to the degree to which we diversify our training programs and our faculty, and there needs to be consequences to not doing so.”

No funding for the study was reported.

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

Oncology fellows who completed diversity, equity, and inclusion (DEI) training report that they feel more confident about responding to different types of discrimination, both when directed at them personally and when directed at others.

The finding comes from a survey conducted after the introduction of DEI training within the Yale Medical Oncology-Hematology Fellowship Program. The study was reported by Norin Ansari, MD, MPH, of Yale Cancer Center, New Haven, Conn., at the annual meeting of the American Society of Clinical Oncology (ASCO).

Dr. Ansari emphasized the DEI curriculum in fellowship programs by highlighting the racial and gender disparities that exist among physicians.

“There is a significant representation problem – only 2%-3% of practicing oncologists are Black or Hispanic/Latino,” she said. “And that representation decreases with each stage in the pipeline of the workforce.”

Dr. Ansari also noted gender disparities in the oncologist workforce, reporting that about one-third of faculty positions are held by women.

The anonymous survey was sent to 29 fellows; 23 responded, including 8 first-year fellows and 13 senior fellows. Over 57% of respondents rated the importance of DEI education as 10 on a 10-point scale (mean, 8.6).

At the start of this year, the responses of senior fellows who had already received some DEI training during the previous year’s lecture series were compared with first-year fellows who had not had any fellowship DEI education.

First-year fellows reported a mean confidence score of 2.5/5 at navigating bias and microaggressions when experienced personally and a mean score of 2.9/5 when they were directed at others. Senior fellows reported mean confidence scores of 3 and 3.2, respectively.

Yale then compared longitudinal data on fellows’ comfort levels in navigating discrimination in 2021, 2022, and 2023 a month before the ASCO meeting.

Fellows were asked to rate their comfort level from 1 to 10 in navigating different types of discrimination, including racial inequality, sexual harassment, and gender discrimination. In these three categories, fellows rated comfortability as a 5 in 2021 and as 7 in 2023 after the DEI training.

“Our first goal is to normalize talking about DEI and to recognize that different people in our workforce have different experiences and how we can be allies for them and for our patients,” Dr. Ansari said. “And I think for long-term goals we want to take stock of who’s at the table, who’s making decisions, and how does that affect our field, our science, and our patients.”

Yale designed the 3-year longitudinal curriculum with two annual core topics: upstander training and journal club for discussion and reflection. An additional two to three training sessions per year will focus on either race, gender, LGBTQ+, disability, religion, or implicit bias training.

The most popular topics among fellows were upstander training, cancer treatment and outcomes disparities, recruitment and retention, and career promotion and pay disparities.

The preferred platforms of content delivery were lectures from experts in the field, affinity groups or mentorship links, small group discussions, and advocacy education.

Gerald Hsu, MD, PhD, with the San Francisco VA Medical Center, discussed the results of Yale’s DEI curriculum assessment, saying it represented “best practices” in the industry. However, he acknowledged that realistically, not everyone will be receptive to DEI training.

Dr. Hsu said that holding medical staff accountable is the only way to truly incorporate DEI into everyday practice.

“Collectively, we need to be holding ourselves to different standards or holding ourselves to some standard,” Dr. Hsu said. “Maybe we need to be setting goals to the degree to which we diversify our training programs and our faculty, and there needs to be consequences to not doing so.”

No funding for the study was reported.

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

On Nov. 22, three Food and Drug Administration inspectors arrived at the sprawling Intas Pharmaceuticals plant south of Ahmedabad, India, and found hundreds of trash bags full of shredded documents tossed into a garbage truck. Over the next 10 days, the inspectors assessed what looked like a systematic effort to conceal quality problems at the plant, which provided more than half of the U.S. supply of generic cisplatin and carboplatin, two cheap drugs used to treat as many as 500,000 new cancer cases every year.

Seven months later, doctors and their patients are facing the unimaginable: In California, Virginia, and everywhere in between, they are being forced into grim contemplation of untested rationing plans for breast, cervical, bladder, ovarian, lung, testicular, and other cancers. Their decisions are likely to result in preventable deaths.

Cisplatin and carboplatin are among scores of drugs in shortage, including 12 other cancer drugs, ADHD pills, blood thinners, and antibiotics. COVID-hangover supply chain issues and limited FDA oversight are part of the problem, but the main cause, experts agree, is the underlying weakness of the generic drug industry. Made mostly overseas, these old but crucial drugs are often sold at a loss or for little profit. Domestic manufacturers have little interest in making them, setting their sights instead on high-priced drugs with plump profit margins.

The problem isn’t new, and that’s particularly infuriating to many clinicians. President Joe Biden, whose son Beau died of an aggressive brain cancer, has focused his Cancer Moonshot on discovering cures – undoubtedly expensive ones. Indeed, existing brand-name cancer drugs often cost tens of thousands of dollars a year.

But what about the thousands of patients today who can’t get a drug like cisplatin, approved by the FDA in 1978 and costing as little as $6 a dose?

“It’s just insane,” said Mark Ratain, MD, a cancer doctor and pharmacologist at the University of Chicago. “Your roof is caving in, but you want to build a basketball court in the backyard because your wife is pregnant with twin boys and you want them to be NBA stars when they grow up?”

“It’s just a travesty that this is the level of health care in the United States of America right now,” said Stephen Divers, MD, an oncologist in Hot Springs, Ark., who in recent weeks has had to delay or change treatment for numerous bladder, breast, and ovarian cancer patients because his clinic cannot find enough cisplatin and carboplatin. Results from a survey of academic cancer centers released June 7 found 93% couldn’t find enough carboplatin and 70% had cisplatin shortages.

“All day, in between patients, we hold staff meetings trying to figure this out,” said Bonny Moore, MD, an oncologist in Fredericksburg, Virginia. “It’s the most nauseous I’ve ever felt. Our office stayed open during COVID; we never had to stop treating patients. We got them vaccinated, kept them safe, and now I can’t get them a $10 drug.”

The cancer clinicians KFF Health News interviewed for this story said that, given current shortages, they prioritize patients who can be cured over later-stage patients, in whom the drugs generally can only slow the disease, and for whom alternatives – though sometimes less effective and often with more side effects – are available. But some doctors are even rationing doses intended to cure.

Isabella McDonald, then a junior at Utah Valley University, was diagnosed in April with a rare, often fatal bone cancer, whose sole treatment for young adults includes the drug methotrexate. When Isabella’s second cycle of treatment began June 5, clinicians advised that she would be getting less than the full dose because of a methotrexate shortage, said her father, Brent.

“They don’t think it will have a negative impact on her treatment, but as far as I am aware, there isn’t any scientific basis to make that conclusion,” he said. “As you can imagine, when they gave us such low odds of her beating this cancer, it feels like we want to give it everything we can and not something short of the standard.”

Mr. McDonald stressed that he didn’t blame the staffers at Intermountain Health who take care of Isabella. The family – his other daughter, Cate, made a TikTok video about her sister’s plight – were simply stunned at such a basic flaw in the health care system.

At Dr. Moore’s practice, in Virginia, clinicians gave 60% of the optimal dose of carboplatin to some uterine cancer patients during the week of May 16, then shifted to 80% after a small shipment came in the following week. The doctors had to omit carboplatin from normal combination treatments for patients with recurrent disease, she said.

On June 2, Dr. Moore and colleagues were glued to their drug distributor’s website, anxious as teenagers waiting for Taylor Swift tickets to go on sale – only with mortal consequences at stake.

She later emailed KFF Health News: “Carboplatin did NOT come back in stock today. Neither did cisplatin.”

Doses remained at 80%, she said. Things hadn’t changed 10 days later.
 

Generics manufacturers are pulling out

The causes of shortages are well established. Everyone wants to pay less, and the middlemen who procure and distribute generics keep driving down wholesale prices. The average net price of generic drugs fell by more than half between 2016 and 2022, according to research by Anthony Sardella, a business professor at Washington University in St. Louis.

As generics manufacturers compete to win sales contracts with the big negotiators of such purchases, such as Vizient and Premier, their profits sink. Some are going out of business. Akorn, which made 75 common generics, went bankrupt and closed in February. Israeli generics giant Teva, which has a portfolio of 3,600 medicines, announced May 18 it was shifting to brand-name drugs and “high-value generics.” Lannett, with about 120 generics, announced a Chapter 11 reorganization amid declining revenue. Other companies are in trouble too, said David Gaugh, interim CEO of the Association for Accessible Medicines, the leading generics trade group.

The generics industry used to lose money on about a third of the drugs it produced, but now it’s more like half, Mr. Gaugh said. So when a company stops making a drug, others do not necessarily step up, he said. Officials at Fresenius Kabi and Pfizer said they have increased their carboplatin production since March, but not enough to end the shortage. On June 2, FDA Commissioner Robert Califf announced the agency had given emergency authorization for Chinese-made cisplatin to enter the U.S. market, but the impact of the move wasn’t immediately clear.

Cisplatin and carboplatin are made in special production lines under sterile conditions, and expanding or changing the lines requires FDA approval. Bargain-basement prices have pushed production overseas, where it’s harder for the FDA to track quality standards. The Intas plant inspection was a relative rarity in India, where the FDA in 2022 reportedly inspected only 3% of sites that make drugs for the U.S. market. Mr. Sardella testified in May that a quarter of all U.S. drug prescriptions are filled by companies that received FDA warning letters in the past 26 months. And pharmaceutical industry product recalls are at their highest level in 18 years, reflecting fragile supply conditions.

The FDA listed 137 drugs in shortage as of June 13, including many essential medicines made by few companies.

Intas voluntarily shut down its Ahmedabad plant after the FDA inspection, and the agency posted its shocking inspection report in January. Accord Healthcare, the U.S. subsidiary of Intas, said in mid-June it had no date for restarting production.

Asked why it waited 2 months after its inspection to announce the cisplatin shortage, given that Intas supplied more than half the U.S. market for the drug, the FDA said via email that it doesn’t list a drug in shortage until it has “confirmed that overall market demand is not being met.”

Prices for carboplatin, cisplatin, and other drugs have skyrocketed on the so-called gray market, where speculators sell medicines they snapped up in anticipation of shortages. A 600-mg bottle of carboplatin, normally available for $30, was going for $185 in early May and $345 a week later, said Richard Scanlon, the pharmacist at dr. Moore’s clinic.

“It’s hard to have these conversations with patients – ‘I have your dose for this cycle, but not sure about next cycle,’” said Mark Einstein, MD, chair of the department of obstetrics, gynecology and reproductive health at New Jersey Medical School, Newark.
 

Should government step in?

Despite a drug shortage task force and numerous congressional hearings, progress has been slow at best. The 2020 CARES Act gave the FDA the power to require companies to have contingency plans enabling them to respond to shortages, but the agency has not yet implemented guidance to enforce the provisions.

As a result, neither Accord nor other cisplatin makers had a response plan in place when Intas’ plant was shut down, said Soumi Saha, senior vice president of government affairs for Premier, which arranges wholesale drug purchases for more than 4,400 hospitals and health systems.

Premier understood in December that the shutdown endangered the U.S. supply of cisplatin and carboplatin, but it also didn’t issue an immediate alarm. “It’s a fine balance,” she said. “You don’t want to create panic-buying or hoarding.”

More lasting solutions are under discussion. Mr. Sardella and others have proposed government subsidies to get U.S. generics plants running full time. Their capacity is now half-idle. If federal agencies like the Centers for Medicare & Medicaid Services paid more for more safely and efficiently produced drugs, it would promote a more stable supply chain, he said.

“At a certain point the system needs to recognize there’s a high cost to low-cost drugs,” said Allan Coukell, senior vice president for public policy at Civica Rx, a nonprofit funded by health systems, foundations, and the federal government that provides about 80 drugs to hospitals in its network. Civica is building a $140 million factory near Petersburg, Va., that will produce dozens more, Mr. Coukell said.

Dr. Ratain and his University of Chicago colleague Satyajit Kosuri, MD, recently called for the creation of a strategic inventory buffer for generic medications, something like the Strategic Petroleum Reserve, set up in 1975 in response to the OPEC oil crisis.

In fact, Dr. Ratain reckons, selling a quarter-million barrels of oil would probably generate enough cash to make and store 2 years’ worth of carboplatin and cisplatin.

“It would almost literally be a drop in the bucket.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – an independent source of health policy research, polling, and journalism. Learn more about KFF.

On Nov. 22, three Food and Drug Administration inspectors arrived at the sprawling Intas Pharmaceuticals plant south of Ahmedabad, India, and found hundreds of trash bags full of shredded documents tossed into a garbage truck. Over the next 10 days, the inspectors assessed what looked like a systematic effort to conceal quality problems at the plant, which provided more than half of the U.S. supply of generic cisplatin and carboplatin, two cheap drugs used to treat as many as 500,000 new cancer cases every year.

Seven months later, doctors and their patients are facing the unimaginable: In California, Virginia, and everywhere in between, they are being forced into grim contemplation of untested rationing plans for breast, cervical, bladder, ovarian, lung, testicular, and other cancers. Their decisions are likely to result in preventable deaths.

Cisplatin and carboplatin are among scores of drugs in shortage, including 12 other cancer drugs, ADHD pills, blood thinners, and antibiotics. COVID-hangover supply chain issues and limited FDA oversight are part of the problem, but the main cause, experts agree, is the underlying weakness of the generic drug industry. Made mostly overseas, these old but crucial drugs are often sold at a loss or for little profit. Domestic manufacturers have little interest in making them, setting their sights instead on high-priced drugs with plump profit margins.

The problem isn’t new, and that’s particularly infuriating to many clinicians. President Joe Biden, whose son Beau died of an aggressive brain cancer, has focused his Cancer Moonshot on discovering cures – undoubtedly expensive ones. Indeed, existing brand-name cancer drugs often cost tens of thousands of dollars a year.

But what about the thousands of patients today who can’t get a drug like cisplatin, approved by the FDA in 1978 and costing as little as $6 a dose?

“It’s just insane,” said Mark Ratain, MD, a cancer doctor and pharmacologist at the University of Chicago. “Your roof is caving in, but you want to build a basketball court in the backyard because your wife is pregnant with twin boys and you want them to be NBA stars when they grow up?”

“It’s just a travesty that this is the level of health care in the United States of America right now,” said Stephen Divers, MD, an oncologist in Hot Springs, Ark., who in recent weeks has had to delay or change treatment for numerous bladder, breast, and ovarian cancer patients because his clinic cannot find enough cisplatin and carboplatin. Results from a survey of academic cancer centers released June 7 found 93% couldn’t find enough carboplatin and 70% had cisplatin shortages.

“All day, in between patients, we hold staff meetings trying to figure this out,” said Bonny Moore, MD, an oncologist in Fredericksburg, Virginia. “It’s the most nauseous I’ve ever felt. Our office stayed open during COVID; we never had to stop treating patients. We got them vaccinated, kept them safe, and now I can’t get them a $10 drug.”

The cancer clinicians KFF Health News interviewed for this story said that, given current shortages, they prioritize patients who can be cured over later-stage patients, in whom the drugs generally can only slow the disease, and for whom alternatives – though sometimes less effective and often with more side effects – are available. But some doctors are even rationing doses intended to cure.

Isabella McDonald, then a junior at Utah Valley University, was diagnosed in April with a rare, often fatal bone cancer, whose sole treatment for young adults includes the drug methotrexate. When Isabella’s second cycle of treatment began June 5, clinicians advised that she would be getting less than the full dose because of a methotrexate shortage, said her father, Brent.

“They don’t think it will have a negative impact on her treatment, but as far as I am aware, there isn’t any scientific basis to make that conclusion,” he said. “As you can imagine, when they gave us such low odds of her beating this cancer, it feels like we want to give it everything we can and not something short of the standard.”

Mr. McDonald stressed that he didn’t blame the staffers at Intermountain Health who take care of Isabella. The family – his other daughter, Cate, made a TikTok video about her sister’s plight – were simply stunned at such a basic flaw in the health care system.

At Dr. Moore’s practice, in Virginia, clinicians gave 60% of the optimal dose of carboplatin to some uterine cancer patients during the week of May 16, then shifted to 80% after a small shipment came in the following week. The doctors had to omit carboplatin from normal combination treatments for patients with recurrent disease, she said.

On June 2, Dr. Moore and colleagues were glued to their drug distributor’s website, anxious as teenagers waiting for Taylor Swift tickets to go on sale – only with mortal consequences at stake.

She later emailed KFF Health News: “Carboplatin did NOT come back in stock today. Neither did cisplatin.”

Doses remained at 80%, she said. Things hadn’t changed 10 days later.
 

Generics manufacturers are pulling out

The causes of shortages are well established. Everyone wants to pay less, and the middlemen who procure and distribute generics keep driving down wholesale prices. The average net price of generic drugs fell by more than half between 2016 and 2022, according to research by Anthony Sardella, a business professor at Washington University in St. Louis.

As generics manufacturers compete to win sales contracts with the big negotiators of such purchases, such as Vizient and Premier, their profits sink. Some are going out of business. Akorn, which made 75 common generics, went bankrupt and closed in February. Israeli generics giant Teva, which has a portfolio of 3,600 medicines, announced May 18 it was shifting to brand-name drugs and “high-value generics.” Lannett, with about 120 generics, announced a Chapter 11 reorganization amid declining revenue. Other companies are in trouble too, said David Gaugh, interim CEO of the Association for Accessible Medicines, the leading generics trade group.

The generics industry used to lose money on about a third of the drugs it produced, but now it’s more like half, Mr. Gaugh said. So when a company stops making a drug, others do not necessarily step up, he said. Officials at Fresenius Kabi and Pfizer said they have increased their carboplatin production since March, but not enough to end the shortage. On June 2, FDA Commissioner Robert Califf announced the agency had given emergency authorization for Chinese-made cisplatin to enter the U.S. market, but the impact of the move wasn’t immediately clear.

Cisplatin and carboplatin are made in special production lines under sterile conditions, and expanding or changing the lines requires FDA approval. Bargain-basement prices have pushed production overseas, where it’s harder for the FDA to track quality standards. The Intas plant inspection was a relative rarity in India, where the FDA in 2022 reportedly inspected only 3% of sites that make drugs for the U.S. market. Mr. Sardella testified in May that a quarter of all U.S. drug prescriptions are filled by companies that received FDA warning letters in the past 26 months. And pharmaceutical industry product recalls are at their highest level in 18 years, reflecting fragile supply conditions.

The FDA listed 137 drugs in shortage as of June 13, including many essential medicines made by few companies.

Intas voluntarily shut down its Ahmedabad plant after the FDA inspection, and the agency posted its shocking inspection report in January. Accord Healthcare, the U.S. subsidiary of Intas, said in mid-June it had no date for restarting production.

Asked why it waited 2 months after its inspection to announce the cisplatin shortage, given that Intas supplied more than half the U.S. market for the drug, the FDA said via email that it doesn’t list a drug in shortage until it has “confirmed that overall market demand is not being met.”

Prices for carboplatin, cisplatin, and other drugs have skyrocketed on the so-called gray market, where speculators sell medicines they snapped up in anticipation of shortages. A 600-mg bottle of carboplatin, normally available for $30, was going for $185 in early May and $345 a week later, said Richard Scanlon, the pharmacist at dr. Moore’s clinic.

“It’s hard to have these conversations with patients – ‘I have your dose for this cycle, but not sure about next cycle,’” said Mark Einstein, MD, chair of the department of obstetrics, gynecology and reproductive health at New Jersey Medical School, Newark.
 

Should government step in?

Despite a drug shortage task force and numerous congressional hearings, progress has been slow at best. The 2020 CARES Act gave the FDA the power to require companies to have contingency plans enabling them to respond to shortages, but the agency has not yet implemented guidance to enforce the provisions.

As a result, neither Accord nor other cisplatin makers had a response plan in place when Intas’ plant was shut down, said Soumi Saha, senior vice president of government affairs for Premier, which arranges wholesale drug purchases for more than 4,400 hospitals and health systems.

Premier understood in December that the shutdown endangered the U.S. supply of cisplatin and carboplatin, but it also didn’t issue an immediate alarm. “It’s a fine balance,” she said. “You don’t want to create panic-buying or hoarding.”

More lasting solutions are under discussion. Mr. Sardella and others have proposed government subsidies to get U.S. generics plants running full time. Their capacity is now half-idle. If federal agencies like the Centers for Medicare & Medicaid Services paid more for more safely and efficiently produced drugs, it would promote a more stable supply chain, he said.

“At a certain point the system needs to recognize there’s a high cost to low-cost drugs,” said Allan Coukell, senior vice president for public policy at Civica Rx, a nonprofit funded by health systems, foundations, and the federal government that provides about 80 drugs to hospitals in its network. Civica is building a $140 million factory near Petersburg, Va., that will produce dozens more, Mr. Coukell said.

Dr. Ratain and his University of Chicago colleague Satyajit Kosuri, MD, recently called for the creation of a strategic inventory buffer for generic medications, something like the Strategic Petroleum Reserve, set up in 1975 in response to the OPEC oil crisis.

In fact, Dr. Ratain reckons, selling a quarter-million barrels of oil would probably generate enough cash to make and store 2 years’ worth of carboplatin and cisplatin.

“It would almost literally be a drop in the bucket.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – an independent source of health policy research, polling, and journalism. Learn more about KFF.

On Nov. 22, three Food and Drug Administration inspectors arrived at the sprawling Intas Pharmaceuticals plant south of Ahmedabad, India, and found hundreds of trash bags full of shredded documents tossed into a garbage truck. Over the next 10 days, the inspectors assessed what looked like a systematic effort to conceal quality problems at the plant, which provided more than half of the U.S. supply of generic cisplatin and carboplatin, two cheap drugs used to treat as many as 500,000 new cancer cases every year.

Seven months later, doctors and their patients are facing the unimaginable: In California, Virginia, and everywhere in between, they are being forced into grim contemplation of untested rationing plans for breast, cervical, bladder, ovarian, lung, testicular, and other cancers. Their decisions are likely to result in preventable deaths.

Cisplatin and carboplatin are among scores of drugs in shortage, including 12 other cancer drugs, ADHD pills, blood thinners, and antibiotics. COVID-hangover supply chain issues and limited FDA oversight are part of the problem, but the main cause, experts agree, is the underlying weakness of the generic drug industry. Made mostly overseas, these old but crucial drugs are often sold at a loss or for little profit. Domestic manufacturers have little interest in making them, setting their sights instead on high-priced drugs with plump profit margins.

The problem isn’t new, and that’s particularly infuriating to many clinicians. President Joe Biden, whose son Beau died of an aggressive brain cancer, has focused his Cancer Moonshot on discovering cures – undoubtedly expensive ones. Indeed, existing brand-name cancer drugs often cost tens of thousands of dollars a year.

But what about the thousands of patients today who can’t get a drug like cisplatin, approved by the FDA in 1978 and costing as little as $6 a dose?

“It’s just insane,” said Mark Ratain, MD, a cancer doctor and pharmacologist at the University of Chicago. “Your roof is caving in, but you want to build a basketball court in the backyard because your wife is pregnant with twin boys and you want them to be NBA stars when they grow up?”

“It’s just a travesty that this is the level of health care in the United States of America right now,” said Stephen Divers, MD, an oncologist in Hot Springs, Ark., who in recent weeks has had to delay or change treatment for numerous bladder, breast, and ovarian cancer patients because his clinic cannot find enough cisplatin and carboplatin. Results from a survey of academic cancer centers released June 7 found 93% couldn’t find enough carboplatin and 70% had cisplatin shortages.

“All day, in between patients, we hold staff meetings trying to figure this out,” said Bonny Moore, MD, an oncologist in Fredericksburg, Virginia. “It’s the most nauseous I’ve ever felt. Our office stayed open during COVID; we never had to stop treating patients. We got them vaccinated, kept them safe, and now I can’t get them a $10 drug.”

The cancer clinicians KFF Health News interviewed for this story said that, given current shortages, they prioritize patients who can be cured over later-stage patients, in whom the drugs generally can only slow the disease, and for whom alternatives – though sometimes less effective and often with more side effects – are available. But some doctors are even rationing doses intended to cure.

Isabella McDonald, then a junior at Utah Valley University, was diagnosed in April with a rare, often fatal bone cancer, whose sole treatment for young adults includes the drug methotrexate. When Isabella’s second cycle of treatment began June 5, clinicians advised that she would be getting less than the full dose because of a methotrexate shortage, said her father, Brent.

“They don’t think it will have a negative impact on her treatment, but as far as I am aware, there isn’t any scientific basis to make that conclusion,” he said. “As you can imagine, when they gave us such low odds of her beating this cancer, it feels like we want to give it everything we can and not something short of the standard.”

Mr. McDonald stressed that he didn’t blame the staffers at Intermountain Health who take care of Isabella. The family – his other daughter, Cate, made a TikTok video about her sister’s plight – were simply stunned at such a basic flaw in the health care system.

At Dr. Moore’s practice, in Virginia, clinicians gave 60% of the optimal dose of carboplatin to some uterine cancer patients during the week of May 16, then shifted to 80% after a small shipment came in the following week. The doctors had to omit carboplatin from normal combination treatments for patients with recurrent disease, she said.

On June 2, Dr. Moore and colleagues were glued to their drug distributor’s website, anxious as teenagers waiting for Taylor Swift tickets to go on sale – only with mortal consequences at stake.

She later emailed KFF Health News: “Carboplatin did NOT come back in stock today. Neither did cisplatin.”

Doses remained at 80%, she said. Things hadn’t changed 10 days later.
 

Generics manufacturers are pulling out

The causes of shortages are well established. Everyone wants to pay less, and the middlemen who procure and distribute generics keep driving down wholesale prices. The average net price of generic drugs fell by more than half between 2016 and 2022, according to research by Anthony Sardella, a business professor at Washington University in St. Louis.

As generics manufacturers compete to win sales contracts with the big negotiators of such purchases, such as Vizient and Premier, their profits sink. Some are going out of business. Akorn, which made 75 common generics, went bankrupt and closed in February. Israeli generics giant Teva, which has a portfolio of 3,600 medicines, announced May 18 it was shifting to brand-name drugs and “high-value generics.” Lannett, with about 120 generics, announced a Chapter 11 reorganization amid declining revenue. Other companies are in trouble too, said David Gaugh, interim CEO of the Association for Accessible Medicines, the leading generics trade group.

The generics industry used to lose money on about a third of the drugs it produced, but now it’s more like half, Mr. Gaugh said. So when a company stops making a drug, others do not necessarily step up, he said. Officials at Fresenius Kabi and Pfizer said they have increased their carboplatin production since March, but not enough to end the shortage. On June 2, FDA Commissioner Robert Califf announced the agency had given emergency authorization for Chinese-made cisplatin to enter the U.S. market, but the impact of the move wasn’t immediately clear.

Cisplatin and carboplatin are made in special production lines under sterile conditions, and expanding or changing the lines requires FDA approval. Bargain-basement prices have pushed production overseas, where it’s harder for the FDA to track quality standards. The Intas plant inspection was a relative rarity in India, where the FDA in 2022 reportedly inspected only 3% of sites that make drugs for the U.S. market. Mr. Sardella testified in May that a quarter of all U.S. drug prescriptions are filled by companies that received FDA warning letters in the past 26 months. And pharmaceutical industry product recalls are at their highest level in 18 years, reflecting fragile supply conditions.

The FDA listed 137 drugs in shortage as of June 13, including many essential medicines made by few companies.

Intas voluntarily shut down its Ahmedabad plant after the FDA inspection, and the agency posted its shocking inspection report in January. Accord Healthcare, the U.S. subsidiary of Intas, said in mid-June it had no date for restarting production.

Asked why it waited 2 months after its inspection to announce the cisplatin shortage, given that Intas supplied more than half the U.S. market for the drug, the FDA said via email that it doesn’t list a drug in shortage until it has “confirmed that overall market demand is not being met.”

Prices for carboplatin, cisplatin, and other drugs have skyrocketed on the so-called gray market, where speculators sell medicines they snapped up in anticipation of shortages. A 600-mg bottle of carboplatin, normally available for $30, was going for $185 in early May and $345 a week later, said Richard Scanlon, the pharmacist at dr. Moore’s clinic.

“It’s hard to have these conversations with patients – ‘I have your dose for this cycle, but not sure about next cycle,’” said Mark Einstein, MD, chair of the department of obstetrics, gynecology and reproductive health at New Jersey Medical School, Newark.
 

Should government step in?

Despite a drug shortage task force and numerous congressional hearings, progress has been slow at best. The 2020 CARES Act gave the FDA the power to require companies to have contingency plans enabling them to respond to shortages, but the agency has not yet implemented guidance to enforce the provisions.

As a result, neither Accord nor other cisplatin makers had a response plan in place when Intas’ plant was shut down, said Soumi Saha, senior vice president of government affairs for Premier, which arranges wholesale drug purchases for more than 4,400 hospitals and health systems.

Premier understood in December that the shutdown endangered the U.S. supply of cisplatin and carboplatin, but it also didn’t issue an immediate alarm. “It’s a fine balance,” she said. “You don’t want to create panic-buying or hoarding.”

More lasting solutions are under discussion. Mr. Sardella and others have proposed government subsidies to get U.S. generics plants running full time. Their capacity is now half-idle. If federal agencies like the Centers for Medicare & Medicaid Services paid more for more safely and efficiently produced drugs, it would promote a more stable supply chain, he said.

“At a certain point the system needs to recognize there’s a high cost to low-cost drugs,” said Allan Coukell, senior vice president for public policy at Civica Rx, a nonprofit funded by health systems, foundations, and the federal government that provides about 80 drugs to hospitals in its network. Civica is building a $140 million factory near Petersburg, Va., that will produce dozens more, Mr. Coukell said.

Dr. Ratain and his University of Chicago colleague Satyajit Kosuri, MD, recently called for the creation of a strategic inventory buffer for generic medications, something like the Strategic Petroleum Reserve, set up in 1975 in response to the OPEC oil crisis.

In fact, Dr. Ratain reckons, selling a quarter-million barrels of oil would probably generate enough cash to make and store 2 years’ worth of carboplatin and cisplatin.

“It would almost literally be a drop in the bucket.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – an independent source of health policy research, polling, and journalism. Learn more about KFF.

Key clinical point: In transplant-ineligible patients with untreated mantle cell lymphoma (MCL), bendamustine, rituximab, ibrutinib, and rituximab maintenance (BR-Ibrutinib+R) and bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) should be the preferred immunotherapy regimens for improving progression-free survival (PFS) and overall survival (OS), respectively.

Major finding: BR-Ibrutinib+R resulted in the best PFS, with a surface under the cumulative ranking curve (SUCRA) of 0.89 and probability of being the best treatment (PbBT) of 69% followed by bendamustine, rituximab, and rituximab maintenance (SUCRA 0.76; PbBT 11%). VR-CAP provided the best OS, with a SUCRA of 0.89 and PbBT of 63% followed by bendamustine and rituximab regimen (SUCRA 0.74; PbBT 22%).

Study details: The data come from a network meta-analysis of nine randomized controlled trials involving 2897 transplant-ineligible patients who received first-line chemoimmunotherapy for MCL.

Disclosures: This study was funded by the Achievement Transformation Project and others. The authors declared no conflicts of interest.

Source: Jing C et al. Efficacy of front-line immunochemotherapy for transplant-ineligible mantle cell lymphoma: A network meta-analysis of randomized controlled trials. Cancer Med. 2023 (Jun 1). doi: 10.1002/cam4.6183

Key clinical point: In transplant-ineligible patients with untreated mantle cell lymphoma (MCL), bendamustine, rituximab, ibrutinib, and rituximab maintenance (BR-Ibrutinib+R) and bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) should be the preferred immunotherapy regimens for improving progression-free survival (PFS) and overall survival (OS), respectively.

Major finding: BR-Ibrutinib+R resulted in the best PFS, with a surface under the cumulative ranking curve (SUCRA) of 0.89 and probability of being the best treatment (PbBT) of 69% followed by bendamustine, rituximab, and rituximab maintenance (SUCRA 0.76; PbBT 11%). VR-CAP provided the best OS, with a SUCRA of 0.89 and PbBT of 63% followed by bendamustine and rituximab regimen (SUCRA 0.74; PbBT 22%).

Study details: The data come from a network meta-analysis of nine randomized controlled trials involving 2897 transplant-ineligible patients who received first-line chemoimmunotherapy for MCL.

Disclosures: This study was funded by the Achievement Transformation Project and others. The authors declared no conflicts of interest.

Source: Jing C et al. Efficacy of front-line immunochemotherapy for transplant-ineligible mantle cell lymphoma: A network meta-analysis of randomized controlled trials. Cancer Med. 2023 (Jun 1). doi: 10.1002/cam4.6183

Key clinical point: In transplant-ineligible patients with untreated mantle cell lymphoma (MCL), bendamustine, rituximab, ibrutinib, and rituximab maintenance (BR-Ibrutinib+R) and bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) should be the preferred immunotherapy regimens for improving progression-free survival (PFS) and overall survival (OS), respectively.

Major finding: BR-Ibrutinib+R resulted in the best PFS, with a surface under the cumulative ranking curve (SUCRA) of 0.89 and probability of being the best treatment (PbBT) of 69% followed by bendamustine, rituximab, and rituximab maintenance (SUCRA 0.76; PbBT 11%). VR-CAP provided the best OS, with a SUCRA of 0.89 and PbBT of 63% followed by bendamustine and rituximab regimen (SUCRA 0.74; PbBT 22%).

Study details: The data come from a network meta-analysis of nine randomized controlled trials involving 2897 transplant-ineligible patients who received first-line chemoimmunotherapy for MCL.

Disclosures: This study was funded by the Achievement Transformation Project and others. The authors declared no conflicts of interest.

Source: Jing C et al. Efficacy of front-line immunochemotherapy for transplant-ineligible mantle cell lymphoma: A network meta-analysis of randomized controlled trials. Cancer Med. 2023 (Jun 1). doi: 10.1002/cam4.6183

Key clinical point: The combination of obinutuzumab and bendamustine is a potent treatment option with a manageable safety profile for patients with relapsed or refractory chronic lymphocytic leukemia (CLL).

Major finding: At a median follow-up of 33.4 months, the median progression-free survival was 26.0 (95% CI 20.3-31.7) months and the median overall survival was not reached. The overall response rate was 78.6%, with 28.6% of patients achieving complete response. The grade ≥3 adverse event (AE) rate was 76.4%, with neutropenia (58.3%), thrombocytopenia (26.4%), and febrile neutropenia (11.1%) being the most common grade ≥3 AE.

Study details: Findings are from the multicenter, phase 2 GABRIELL study that included 72 adult patients with relapsed or refractory CLL who received ≤6 cycles of obinutuzumab plus bendamustine.

Disclosures: This study was funded by Roche Farma SA. Some authors declared serving as advisory board or speaker bureau members with or without honoraria and receiving research support or attendance fees and travel expenses from Roche or others.

Source: Bravo J et al on behalf of the GABRIELL Study Group/Investigators. Obinutuzumab plus bendamustine for relapsed/refractory chronic lymphocytic leukemia and predictive and prognostic impact of genetic alterations: The phase II GABRIELL study. Leuk Lymphoma. 2023;64(5):913-926 (May 31). doi: 10.1080/10428194.2023.2216327

Key clinical point: The combination of obinutuzumab and bendamustine is a potent treatment option with a manageable safety profile for patients with relapsed or refractory chronic lymphocytic leukemia (CLL).

Major finding: At a median follow-up of 33.4 months, the median progression-free survival was 26.0 (95% CI 20.3-31.7) months and the median overall survival was not reached. The overall response rate was 78.6%, with 28.6% of patients achieving complete response. The grade ≥3 adverse event (AE) rate was 76.4%, with neutropenia (58.3%), thrombocytopenia (26.4%), and febrile neutropenia (11.1%) being the most common grade ≥3 AE.

Study details: Findings are from the multicenter, phase 2 GABRIELL study that included 72 adult patients with relapsed or refractory CLL who received ≤6 cycles of obinutuzumab plus bendamustine.

Disclosures: This study was funded by Roche Farma SA. Some authors declared serving as advisory board or speaker bureau members with or without honoraria and receiving research support or attendance fees and travel expenses from Roche or others.

Source: Bravo J et al on behalf of the GABRIELL Study Group/Investigators. Obinutuzumab plus bendamustine for relapsed/refractory chronic lymphocytic leukemia and predictive and prognostic impact of genetic alterations: The phase II GABRIELL study. Leuk Lymphoma. 2023;64(5):913-926 (May 31). doi: 10.1080/10428194.2023.2216327

Key clinical point: The combination of obinutuzumab and bendamustine is a potent treatment option with a manageable safety profile for patients with relapsed or refractory chronic lymphocytic leukemia (CLL).

Major finding: At a median follow-up of 33.4 months, the median progression-free survival was 26.0 (95% CI 20.3-31.7) months and the median overall survival was not reached. The overall response rate was 78.6%, with 28.6% of patients achieving complete response. The grade ≥3 adverse event (AE) rate was 76.4%, with neutropenia (58.3%), thrombocytopenia (26.4%), and febrile neutropenia (11.1%) being the most common grade ≥3 AE.

Study details: Findings are from the multicenter, phase 2 GABRIELL study that included 72 adult patients with relapsed or refractory CLL who received ≤6 cycles of obinutuzumab plus bendamustine.

Disclosures: This study was funded by Roche Farma SA. Some authors declared serving as advisory board or speaker bureau members with or without honoraria and receiving research support or attendance fees and travel expenses from Roche or others.

Source: Bravo J et al on behalf of the GABRIELL Study Group/Investigators. Obinutuzumab plus bendamustine for relapsed/refractory chronic lymphocytic leukemia and predictive and prognostic impact of genetic alterations: The phase II GABRIELL study. Leuk Lymphoma. 2023;64(5):913-926 (May 31). doi: 10.1080/10428194.2023.2216327

Key clinical point: Compared with chemoimmunotherapy (CIT), Bruton tyrosine kinase inhibitor (BTKi) therapy combined with anti-CD20 antibody therapy improves clinical outcomes in patients with treatment-naive chronic lymphocytic leukemia (CLL) without causing increased toxicity.

Major finding: Patients receiving BTKi+anti-CD20 antibody vs CIT had significantly prolonged progression-free survival (hazard ratio 0.25; 95% CI 0.15-0.42) and higher objective response rates (risk ratio [RR] 1.16; 95% CI 1.13-1.20) and a comparable risk for grade ≥3 adverse events (RR 1.04; 95% CI 0.92-1.17).

Study details: The data come from a meta-analysis of four randomized controlled trials involving 1479 patients with treatment-naive CLL who had been randomized to receive CIT or BTKi+anti-CD20 antibody therapy.

Disclosures: This study was partly supported by the Ministry of Science and Technology, Taiwan, and Taipei Medical University, Taiwan. The authors declared no conflicts of interest.

Source: Nguyen TT et al. Efficacy and safety of Bruton tyrosine kinase inhibitor plus anti-CD20 antibody therapy compared with chemoimmunotherapy as front-line treatment for chronic lymphocytic leukemia: A systematic review and meta-analysis of randomized controlled trials. J Immunother. 2023 (May 23). doi: 10.1097/CJI.0000000000000471

Key clinical point: Compared with chemoimmunotherapy (CIT), Bruton tyrosine kinase inhibitor (BTKi) therapy combined with anti-CD20 antibody therapy improves clinical outcomes in patients with treatment-naive chronic lymphocytic leukemia (CLL) without causing increased toxicity.

Major finding: Patients receiving BTKi+anti-CD20 antibody vs CIT had significantly prolonged progression-free survival (hazard ratio 0.25; 95% CI 0.15-0.42) and higher objective response rates (risk ratio [RR] 1.16; 95% CI 1.13-1.20) and a comparable risk for grade ≥3 adverse events (RR 1.04; 95% CI 0.92-1.17).

Study details: The data come from a meta-analysis of four randomized controlled trials involving 1479 patients with treatment-naive CLL who had been randomized to receive CIT or BTKi+anti-CD20 antibody therapy.

Disclosures: This study was partly supported by the Ministry of Science and Technology, Taiwan, and Taipei Medical University, Taiwan. The authors declared no conflicts of interest.

Source: Nguyen TT et al. Efficacy and safety of Bruton tyrosine kinase inhibitor plus anti-CD20 antibody therapy compared with chemoimmunotherapy as front-line treatment for chronic lymphocytic leukemia: A systematic review and meta-analysis of randomized controlled trials. J Immunother. 2023 (May 23). doi: 10.1097/CJI.0000000000000471

Key clinical point: Compared with chemoimmunotherapy (CIT), Bruton tyrosine kinase inhibitor (BTKi) therapy combined with anti-CD20 antibody therapy improves clinical outcomes in patients with treatment-naive chronic lymphocytic leukemia (CLL) without causing increased toxicity.

Major finding: Patients receiving BTKi+anti-CD20 antibody vs CIT had significantly prolonged progression-free survival (hazard ratio 0.25; 95% CI 0.15-0.42) and higher objective response rates (risk ratio [RR] 1.16; 95% CI 1.13-1.20) and a comparable risk for grade ≥3 adverse events (RR 1.04; 95% CI 0.92-1.17).

Study details: The data come from a meta-analysis of four randomized controlled trials involving 1479 patients with treatment-naive CLL who had been randomized to receive CIT or BTKi+anti-CD20 antibody therapy.

Disclosures: This study was partly supported by the Ministry of Science and Technology, Taiwan, and Taipei Medical University, Taiwan. The authors declared no conflicts of interest.

Source: Nguyen TT et al. Efficacy and safety of Bruton tyrosine kinase inhibitor plus anti-CD20 antibody therapy compared with chemoimmunotherapy as front-line treatment for chronic lymphocytic leukemia: A systematic review and meta-analysis of randomized controlled trials. J Immunother. 2023 (May 23). doi: 10.1097/CJI.0000000000000471

Key clinical point: High-dose rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-High-CHOP)/cyclophosphamide, high-dose cytarabine, dexamethasone, etoposide, and rituximab (CHASER) followed by high-dose chemotherapy (HDC) with melphalan, cyclophosphamide, etoposide, and dexamethasone (LEED), and autologous peripheral blood stem cell transplantation (auto-PBSCT) provided favorable long-term survival outcomes in younger patients with untreated advanced mantle cell lymphoma (MCL).

Major finding: At 6-year median follow-up, the 5- and 8-year progression-free survival rates were 52.3% (95% CI 36.7%-65.7%) and 17.1% (95% CI 5.2%-34.7%), respectively, and the overall survival rates were 75.0% (95% CI 59.4%-85.3%) and 69.0% (95% CI 52.3%-80.9%), respectively. The incidence of secondary malignancies (11.1%) and continuous relapses was high.

Study details: This final analysis of the JCOG0406 study included 45 patients age ≤ 65 years with untreated advanced MCL who received R-High-CHOP/CHASER followed by HDC with LEED and auto-PBSCT.

Disclosures: This study was supported by Health and Labour Sciences Research Grants (Japan) and others. S Nakamura declared being an Editorial Board Member of Cancer Science. Some authors reported ties with various organizations.

Source: Ogura M et al. Long-term follow-up after R-High CHOP/CHASER/LEED with Auto-PBSCT in untreated mantle cell lymphoma-Final analysis of JCOG0406. Cancer Sci. 2023 (May 26). doi: 10.1111/cas.15849

Key clinical point: High-dose rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-High-CHOP)/cyclophosphamide, high-dose cytarabine, dexamethasone, etoposide, and rituximab (CHASER) followed by high-dose chemotherapy (HDC) with melphalan, cyclophosphamide, etoposide, and dexamethasone (LEED), and autologous peripheral blood stem cell transplantation (auto-PBSCT) provided favorable long-term survival outcomes in younger patients with untreated advanced mantle cell lymphoma (MCL).

Major finding: At 6-year median follow-up, the 5- and 8-year progression-free survival rates were 52.3% (95% CI 36.7%-65.7%) and 17.1% (95% CI 5.2%-34.7%), respectively, and the overall survival rates were 75.0% (95% CI 59.4%-85.3%) and 69.0% (95% CI 52.3%-80.9%), respectively. The incidence of secondary malignancies (11.1%) and continuous relapses was high.

Study details: This final analysis of the JCOG0406 study included 45 patients age ≤ 65 years with untreated advanced MCL who received R-High-CHOP/CHASER followed by HDC with LEED and auto-PBSCT.

Disclosures: This study was supported by Health and Labour Sciences Research Grants (Japan) and others. S Nakamura declared being an Editorial Board Member of Cancer Science. Some authors reported ties with various organizations.

Source: Ogura M et al. Long-term follow-up after R-High CHOP/CHASER/LEED with Auto-PBSCT in untreated mantle cell lymphoma-Final analysis of JCOG0406. Cancer Sci. 2023 (May 26). doi: 10.1111/cas.15849

Key clinical point: High-dose rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-High-CHOP)/cyclophosphamide, high-dose cytarabine, dexamethasone, etoposide, and rituximab (CHASER) followed by high-dose chemotherapy (HDC) with melphalan, cyclophosphamide, etoposide, and dexamethasone (LEED), and autologous peripheral blood stem cell transplantation (auto-PBSCT) provided favorable long-term survival outcomes in younger patients with untreated advanced mantle cell lymphoma (MCL).

Major finding: At 6-year median follow-up, the 5- and 8-year progression-free survival rates were 52.3% (95% CI 36.7%-65.7%) and 17.1% (95% CI 5.2%-34.7%), respectively, and the overall survival rates were 75.0% (95% CI 59.4%-85.3%) and 69.0% (95% CI 52.3%-80.9%), respectively. The incidence of secondary malignancies (11.1%) and continuous relapses was high.

Study details: This final analysis of the JCOG0406 study included 45 patients age ≤ 65 years with untreated advanced MCL who received R-High-CHOP/CHASER followed by HDC with LEED and auto-PBSCT.

Disclosures: This study was supported by Health and Labour Sciences Research Grants (Japan) and others. S Nakamura declared being an Editorial Board Member of Cancer Science. Some authors reported ties with various organizations.

Source: Ogura M et al. Long-term follow-up after R-High CHOP/CHASER/LEED with Auto-PBSCT in untreated mantle cell lymphoma-Final analysis of JCOG0406. Cancer Sci. 2023 (May 26). doi: 10.1111/cas.15849

Key clinical point: Compared with polatuzumab vedotin+bendamustine+rituximab (pola-BR) and rituximab+lenalidomide (R2), tafasitamab+lenalidomide provided a significant survival benefit in patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL).

Major finding: A significant overall survival (OS) benefit was observed with tafasitamab+lenalidomide vs pola-BR (hazard ratio [HR] 0.441; P = .034) and R2 (HR 0.435; P = .012). However, the OS was similar between the tafasitamab+lenalidomide and CD19-chimeric antigen receptor T-cell groups (CAR-T; HR 0.953; P = .892).

Study details: This expanded analysis of the RE-MIND2 study of propensity score-matched transplant-ineligible patients with R/R DLBCL treated with ≥2 systemic therapies who received tafasitamab+lenalidomide in the L-MIND trial and those who received pola-BR (24 pairs), R2 (33 pairs), or CAR-T (37 pairs) from an observational cohort.

Disclosures: This study was sponsored by MorphoSys AG. Some authors declared serving as consultants, advisory board members, or speakers and receiving research funding, honoraria, or travel support from MorphoSys and others. Four authors declared being employees of or holding equities in MorphoSys.

Source: Nowakowski GS et al. RE-MIND2: Comparative effectiveness of tafasitamab plus lenalidomide versus polatuzumab vedotin/bendamustine/rituximab (pola‑BR), CAR‑T therapies, and lenalidomide/rituximab (R2) based on real‑world data in patients with relapsed/refractory diffuse large B‑cell lymphoma. Ann Hematol. 2023;102:1773-1787 (May 12). doi: 10.1007/s00277-023-05196-4

Key clinical point: Compared with polatuzumab vedotin+bendamustine+rituximab (pola-BR) and rituximab+lenalidomide (R2), tafasitamab+lenalidomide provided a significant survival benefit in patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL).

Major finding: A significant overall survival (OS) benefit was observed with tafasitamab+lenalidomide vs pola-BR (hazard ratio [HR] 0.441; P = .034) and R2 (HR 0.435; P = .012). However, the OS was similar between the tafasitamab+lenalidomide and CD19-chimeric antigen receptor T-cell groups (CAR-T; HR 0.953; P = .892).

Study details: This expanded analysis of the RE-MIND2 study of propensity score-matched transplant-ineligible patients with R/R DLBCL treated with ≥2 systemic therapies who received tafasitamab+lenalidomide in the L-MIND trial and those who received pola-BR (24 pairs), R2 (33 pairs), or CAR-T (37 pairs) from an observational cohort.

Disclosures: This study was sponsored by MorphoSys AG. Some authors declared serving as consultants, advisory board members, or speakers and receiving research funding, honoraria, or travel support from MorphoSys and others. Four authors declared being employees of or holding equities in MorphoSys.

Source: Nowakowski GS et al. RE-MIND2: Comparative effectiveness of tafasitamab plus lenalidomide versus polatuzumab vedotin/bendamustine/rituximab (pola‑BR), CAR‑T therapies, and lenalidomide/rituximab (R2) based on real‑world data in patients with relapsed/refractory diffuse large B‑cell lymphoma. Ann Hematol. 2023;102:1773-1787 (May 12). doi: 10.1007/s00277-023-05196-4

Key clinical point: Compared with polatuzumab vedotin+bendamustine+rituximab (pola-BR) and rituximab+lenalidomide (R2), tafasitamab+lenalidomide provided a significant survival benefit in patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL).

Major finding: A significant overall survival (OS) benefit was observed with tafasitamab+lenalidomide vs pola-BR (hazard ratio [HR] 0.441; P = .034) and R2 (HR 0.435; P = .012). However, the OS was similar between the tafasitamab+lenalidomide and CD19-chimeric antigen receptor T-cell groups (CAR-T; HR 0.953; P = .892).

Study details: This expanded analysis of the RE-MIND2 study of propensity score-matched transplant-ineligible patients with R/R DLBCL treated with ≥2 systemic therapies who received tafasitamab+lenalidomide in the L-MIND trial and those who received pola-BR (24 pairs), R2 (33 pairs), or CAR-T (37 pairs) from an observational cohort.

Disclosures: This study was sponsored by MorphoSys AG. Some authors declared serving as consultants, advisory board members, or speakers and receiving research funding, honoraria, or travel support from MorphoSys and others. Four authors declared being employees of or holding equities in MorphoSys.

Source: Nowakowski GS et al. RE-MIND2: Comparative effectiveness of tafasitamab plus lenalidomide versus polatuzumab vedotin/bendamustine/rituximab (pola‑BR), CAR‑T therapies, and lenalidomide/rituximab (R2) based on real‑world data in patients with relapsed/refractory diffuse large B‑cell lymphoma. Ann Hematol. 2023;102:1773-1787 (May 12). doi: 10.1007/s00277-023-05196-4

Key clinical point: The rituximab, bendamustine, and low-dose cytarabine (R-BAC) regimen, not succeeded by maintenance therapy, induces long-term responses in previously untreated elderly patients with mantle cell lymphoma (MCL).

Major finding: After a median follow-up of 86 months, the median overall survival (OS) and progression-free survival (PFS) were not reached; the 7-year PFS and OS rates were 55% (95% CI 41%-67%) and 63% (95% CI 49%-74%), respectively. The 7-year duration of response rate among the 52 responding patients was 59% (95% CI 44%-71%). No signal of late toxicity was reported.

Study details: Findings are from a long-term analysis of the FIL-RBAC500 trial that included 57 previously untreated elderly patients with MCL who received the R-BAC regimen.

Disclosures: This study was supported by Progetto di Ricerca Sanitaria Finalizzata (Italy) grants and other sources. Some authors declared serving as advisory board members or consultants and receiving research funding, speaker honoraria, or travel expenses and accommodations from various sources.

Source: Tisi MC et al. Long term follow-up of rituximab plus bendamustine and cytarabine (R-BAC) in elderly patients with newly diagnosed MCL. Blood Adv. 2023 (May 12). doi: 10.1182/bloodadvances.2023009744

Key clinical point: The rituximab, bendamustine, and low-dose cytarabine (R-BAC) regimen, not succeeded by maintenance therapy, induces long-term responses in previously untreated elderly patients with mantle cell lymphoma (MCL).

Major finding: After a median follow-up of 86 months, the median overall survival (OS) and progression-free survival (PFS) were not reached; the 7-year PFS and OS rates were 55% (95% CI 41%-67%) and 63% (95% CI 49%-74%), respectively. The 7-year duration of response rate among the 52 responding patients was 59% (95% CI 44%-71%). No signal of late toxicity was reported.

Study details: Findings are from a long-term analysis of the FIL-RBAC500 trial that included 57 previously untreated elderly patients with MCL who received the R-BAC regimen.

Disclosures: This study was supported by Progetto di Ricerca Sanitaria Finalizzata (Italy) grants and other sources. Some authors declared serving as advisory board members or consultants and receiving research funding, speaker honoraria, or travel expenses and accommodations from various sources.

Source: Tisi MC et al. Long term follow-up of rituximab plus bendamustine and cytarabine (R-BAC) in elderly patients with newly diagnosed MCL. Blood Adv. 2023 (May 12). doi: 10.1182/bloodadvances.2023009744

Key clinical point: The rituximab, bendamustine, and low-dose cytarabine (R-BAC) regimen, not succeeded by maintenance therapy, induces long-term responses in previously untreated elderly patients with mantle cell lymphoma (MCL).

Major finding: After a median follow-up of 86 months, the median overall survival (OS) and progression-free survival (PFS) were not reached; the 7-year PFS and OS rates were 55% (95% CI 41%-67%) and 63% (95% CI 49%-74%), respectively. The 7-year duration of response rate among the 52 responding patients was 59% (95% CI 44%-71%). No signal of late toxicity was reported.

Study details: Findings are from a long-term analysis of the FIL-RBAC500 trial that included 57 previously untreated elderly patients with MCL who received the R-BAC regimen.

Disclosures: This study was supported by Progetto di Ricerca Sanitaria Finalizzata (Italy) grants and other sources. Some authors declared serving as advisory board members or consultants and receiving research funding, speaker honoraria, or travel expenses and accommodations from various sources.

Source: Tisi MC et al. Long term follow-up of rituximab plus bendamustine and cytarabine (R-BAC) in elderly patients with newly diagnosed MCL. Blood Adv. 2023 (May 12). doi: 10.1182/bloodadvances.2023009744

Key clinical point: First-line ibrutinib+venetoclax led to high response and survival rates in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) regardless of high-risk genomic features generally associated with poor outcomes.

Major finding: Overall response and 36-month overall survival rates were >95% regardless of high-risk features. Patients with and without high-risk features had similar complete response (61% [95% CI 53%-70%] and 53% [95% CI 41%-65%], respectively) and 36-month progression-free survival (88% [95% CI 81%-93%] and 92% [95% CI 82%-97%], respectively) rates.

Study details: This post hoc analysis of the CAPTIVATE trial analyzed the pooled data of 195 patients with previously untreated CLL/SLL and known status of high-risk features [del(17p), TP53 mutation, and unmutated immunoglobulin heavy chain] treated with fixed-duration ibrutinib+venetoclax, of which 129 had ≥1 high-risk feature.

Disclosures: This study was funded by Pharmacyclics LLC, an AbbVie Company. Some authors declared receiving grants, personal fees, or other support from Pharmacyclics, AbbVie, or others. Two authors declared being employees of Pharmacyclics or AbbVie or having stock or other ownership interests in AbbVie.

Source: Allan JN et al. Outcomes in patients with high-risk features after fixed-duration ibrutinib plus venetoclax: Phase II CAPTIVATE study in first-line chronic lymphocytic leukemia. Clin Cancer Res. 2023 (Jun 7). doi: 10.1158/1078-0432.CCR-22-2779

Key clinical point: First-line ibrutinib+venetoclax led to high response and survival rates in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) regardless of high-risk genomic features generally associated with poor outcomes.

Major finding: Overall response and 36-month overall survival rates were >95% regardless of high-risk features. Patients with and without high-risk features had similar complete response (61% [95% CI 53%-70%] and 53% [95% CI 41%-65%], respectively) and 36-month progression-free survival (88% [95% CI 81%-93%] and 92% [95% CI 82%-97%], respectively) rates.

Study details: This post hoc analysis of the CAPTIVATE trial analyzed the pooled data of 195 patients with previously untreated CLL/SLL and known status of high-risk features [del(17p), TP53 mutation, and unmutated immunoglobulin heavy chain] treated with fixed-duration ibrutinib+venetoclax, of which 129 had ≥1 high-risk feature.

Disclosures: This study was funded by Pharmacyclics LLC, an AbbVie Company. Some authors declared receiving grants, personal fees, or other support from Pharmacyclics, AbbVie, or others. Two authors declared being employees of Pharmacyclics or AbbVie or having stock or other ownership interests in AbbVie.

Source: Allan JN et al. Outcomes in patients with high-risk features after fixed-duration ibrutinib plus venetoclax: Phase II CAPTIVATE study in first-line chronic lymphocytic leukemia. Clin Cancer Res. 2023 (Jun 7). doi: 10.1158/1078-0432.CCR-22-2779

Key clinical point: First-line ibrutinib+venetoclax led to high response and survival rates in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) regardless of high-risk genomic features generally associated with poor outcomes.

Major finding: Overall response and 36-month overall survival rates were >95% regardless of high-risk features. Patients with and without high-risk features had similar complete response (61% [95% CI 53%-70%] and 53% [95% CI 41%-65%], respectively) and 36-month progression-free survival (88% [95% CI 81%-93%] and 92% [95% CI 82%-97%], respectively) rates.

Study details: This post hoc analysis of the CAPTIVATE trial analyzed the pooled data of 195 patients with previously untreated CLL/SLL and known status of high-risk features [del(17p), TP53 mutation, and unmutated immunoglobulin heavy chain] treated with fixed-duration ibrutinib+venetoclax, of which 129 had ≥1 high-risk feature.

Disclosures: This study was funded by Pharmacyclics LLC, an AbbVie Company. Some authors declared receiving grants, personal fees, or other support from Pharmacyclics, AbbVie, or others. Two authors declared being employees of Pharmacyclics or AbbVie or having stock or other ownership interests in AbbVie.

Source: Allan JN et al. Outcomes in patients with high-risk features after fixed-duration ibrutinib plus venetoclax: Phase II CAPTIVATE study in first-line chronic lymphocytic leukemia. Clin Cancer Res. 2023 (Jun 7). doi: 10.1158/1078-0432.CCR-22-2779