Non-Hodgkin Lymphoma

Shortages of carboplatin and cisplatin have become widespread among major cancer centers, according to a survey released this week from the National Comprehensive Cancer Network.

The survey, which included responses from 27 NCCN member institutions, revealed that 93% are experiencing a shortage of carboplatin and that 70% have reported a shortage of cisplatin.

“This is an unacceptable situation,” Robert W. Carlson, MD, NCCN’s chief executive offer, said in the statement released by the network.

“We are hearing from oncologists and pharmacists across the country who have to scramble to find appropriate alternatives for treating their patients with cancer right now,” Dr. Carlson said. And while the survey results show patients are still able to get lifesaving care, “it comes at a burden to our overtaxed medical facilities.”

The NCCN called on the federal government, the pharmaceutical industry, providers, and payers to take steps to “help mitigate any impacts” from this cancer drug shortage.

“We need to work together to improve the current situation and prevent it from happening again in the future,” Dr. Carlson stressed.

Carboplatin and cisplatin, which are frequently used together for systemic treatment, are highly effective therapies prescribed to treat many cancer types, including lung, breast, and prostate cancers, as well as leukemias and lymphomas. An estimated 500,000 new patients with cancer receive these agents each year.

The current survey, conducted over the last week of May, found that 100% of responding centers are able to continue to treat patients who need cisplatin without delays.

The same cannot be said for carboplatin: only 64% of centers said they are still able to continue treating all current patients receiving the platinum-based therapy. Among 19 responding centers, 20% reported that they were continuing carboplatin regimens for some but not all patients. And 16% reported treatment delays from having to obtain prior authorization for modified treatment plans, though none reported denials.

“Carboplatin has been in short supply for months but in the last 4 weeks has reached a critical stage,” according to one survey comment. “Without additional inventory many of our sites will be out of drug by early next week.”

In response to the survey question, “Is your center experiencing a shortage of carboplatin,” others made similar comments:

• “Current shipments from established manufacturers have been paused.”
• “The supply of carboplatin available is not meeting our demands.”
• “Without additional supply in early June, we will have to implement several shortage mitigation strategies.”

Survey respondents also addressed whether manufacturers or suppliers have provided any indication of when these drugs will become readily available again. For both drugs, about 60% of respondents said no. And for those who do receive updates, many noted that the “information is tentative and variable.”

Respondents indicated that other cancer agents, including methotrexate (67%) and 5FU (26%), are also in short supply at their centers.

The shortage and the uncertainty as to when it will end are forcing some centers to develop conservation and mitigation strategies.

The NCCN has broadly outlined how the federal government, the pharmaceutical industry, providers, and payers can help with prevention and mitigation. The NCCN has called on the federal government and the pharmaceutical industry to work to secure a steady supply of core anticancer drugs and has asked payers to “put patients first and provide flexible and efficient systems of providing coverage for alternative therapies replacing anti-cancer drugs that are unavailable or in shortage.”

Overall, the survey results “demonstrate the widespread impact of the chemotherapy shortage,” said Alyssa Schatz, MSW, senior director of policy and advocacy for NCCN. “We hope that by sharing this survey and calling for united action across the oncology community, we can come together to prevent future drug shortages and ensure quality, effective, equitable, and accessible cancer care for all.”

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

Shortages of carboplatin and cisplatin have become widespread among major cancer centers, according to a survey released this week from the National Comprehensive Cancer Network.

The survey, which included responses from 27 NCCN member institutions, revealed that 93% are experiencing a shortage of carboplatin and that 70% have reported a shortage of cisplatin.

“This is an unacceptable situation,” Robert W. Carlson, MD, NCCN’s chief executive offer, said in the statement released by the network.

“We are hearing from oncologists and pharmacists across the country who have to scramble to find appropriate alternatives for treating their patients with cancer right now,” Dr. Carlson said. And while the survey results show patients are still able to get lifesaving care, “it comes at a burden to our overtaxed medical facilities.”

The NCCN called on the federal government, the pharmaceutical industry, providers, and payers to take steps to “help mitigate any impacts” from this cancer drug shortage.

“We need to work together to improve the current situation and prevent it from happening again in the future,” Dr. Carlson stressed.

Carboplatin and cisplatin, which are frequently used together for systemic treatment, are highly effective therapies prescribed to treat many cancer types, including lung, breast, and prostate cancers, as well as leukemias and lymphomas. An estimated 500,000 new patients with cancer receive these agents each year.

The current survey, conducted over the last week of May, found that 100% of responding centers are able to continue to treat patients who need cisplatin without delays.

The same cannot be said for carboplatin: only 64% of centers said they are still able to continue treating all current patients receiving the platinum-based therapy. Among 19 responding centers, 20% reported that they were continuing carboplatin regimens for some but not all patients. And 16% reported treatment delays from having to obtain prior authorization for modified treatment plans, though none reported denials.

“Carboplatin has been in short supply for months but in the last 4 weeks has reached a critical stage,” according to one survey comment. “Without additional inventory many of our sites will be out of drug by early next week.”

In response to the survey question, “Is your center experiencing a shortage of carboplatin,” others made similar comments:

• “Current shipments from established manufacturers have been paused.”
• “The supply of carboplatin available is not meeting our demands.”
• “Without additional supply in early June, we will have to implement several shortage mitigation strategies.”

Survey respondents also addressed whether manufacturers or suppliers have provided any indication of when these drugs will become readily available again. For both drugs, about 60% of respondents said no. And for those who do receive updates, many noted that the “information is tentative and variable.”

Respondents indicated that other cancer agents, including methotrexate (67%) and 5FU (26%), are also in short supply at their centers.

The shortage and the uncertainty as to when it will end are forcing some centers to develop conservation and mitigation strategies.

The NCCN has broadly outlined how the federal government, the pharmaceutical industry, providers, and payers can help with prevention and mitigation. The NCCN has called on the federal government and the pharmaceutical industry to work to secure a steady supply of core anticancer drugs and has asked payers to “put patients first and provide flexible and efficient systems of providing coverage for alternative therapies replacing anti-cancer drugs that are unavailable or in shortage.”

Overall, the survey results “demonstrate the widespread impact of the chemotherapy shortage,” said Alyssa Schatz, MSW, senior director of policy and advocacy for NCCN. “We hope that by sharing this survey and calling for united action across the oncology community, we can come together to prevent future drug shortages and ensure quality, effective, equitable, and accessible cancer care for all.”

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

Shortages of carboplatin and cisplatin have become widespread among major cancer centers, according to a survey released this week from the National Comprehensive Cancer Network.

The survey, which included responses from 27 NCCN member institutions, revealed that 93% are experiencing a shortage of carboplatin and that 70% have reported a shortage of cisplatin.

“This is an unacceptable situation,” Robert W. Carlson, MD, NCCN’s chief executive offer, said in the statement released by the network.

“We are hearing from oncologists and pharmacists across the country who have to scramble to find appropriate alternatives for treating their patients with cancer right now,” Dr. Carlson said. And while the survey results show patients are still able to get lifesaving care, “it comes at a burden to our overtaxed medical facilities.”

The NCCN called on the federal government, the pharmaceutical industry, providers, and payers to take steps to “help mitigate any impacts” from this cancer drug shortage.

“We need to work together to improve the current situation and prevent it from happening again in the future,” Dr. Carlson stressed.

Carboplatin and cisplatin, which are frequently used together for systemic treatment, are highly effective therapies prescribed to treat many cancer types, including lung, breast, and prostate cancers, as well as leukemias and lymphomas. An estimated 500,000 new patients with cancer receive these agents each year.

The current survey, conducted over the last week of May, found that 100% of responding centers are able to continue to treat patients who need cisplatin without delays.

The same cannot be said for carboplatin: only 64% of centers said they are still able to continue treating all current patients receiving the platinum-based therapy. Among 19 responding centers, 20% reported that they were continuing carboplatin regimens for some but not all patients. And 16% reported treatment delays from having to obtain prior authorization for modified treatment plans, though none reported denials.

“Carboplatin has been in short supply for months but in the last 4 weeks has reached a critical stage,” according to one survey comment. “Without additional inventory many of our sites will be out of drug by early next week.”

In response to the survey question, “Is your center experiencing a shortage of carboplatin,” others made similar comments:

• “Current shipments from established manufacturers have been paused.”
• “The supply of carboplatin available is not meeting our demands.”
• “Without additional supply in early June, we will have to implement several shortage mitigation strategies.”

Survey respondents also addressed whether manufacturers or suppliers have provided any indication of when these drugs will become readily available again. For both drugs, about 60% of respondents said no. And for those who do receive updates, many noted that the “information is tentative and variable.”

Respondents indicated that other cancer agents, including methotrexate (67%) and 5FU (26%), are also in short supply at their centers.

The shortage and the uncertainty as to when it will end are forcing some centers to develop conservation and mitigation strategies.

The NCCN has broadly outlined how the federal government, the pharmaceutical industry, providers, and payers can help with prevention and mitigation. The NCCN has called on the federal government and the pharmaceutical industry to work to secure a steady supply of core anticancer drugs and has asked payers to “put patients first and provide flexible and efficient systems of providing coverage for alternative therapies replacing anti-cancer drugs that are unavailable or in shortage.”

Overall, the survey results “demonstrate the widespread impact of the chemotherapy shortage,” said Alyssa Schatz, MSW, senior director of policy and advocacy for NCCN. “We hope that by sharing this survey and calling for united action across the oncology community, we can come together to prevent future drug shortages and ensure quality, effective, equitable, and accessible cancer care for all.”

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

The CD19-directed chimeric antigen receptor (CAR) T-cell therapy lisocabtagene maraleucel (liso-cel, Bristol-Myers Squibb), showed efficacy in achieving complete responses among patients with relapsed or refractory chronic lymphocytic leukemia (r/r CLL) or small lymphocytic lymphoma (SLL), after treatment with a Bruton kinase inhibitor (BTKi) and BCL2 inhibitor.

The phase 1/2 TRANSCEND CLL 004 trial represents “the first pivotal multicenter trial to evaluate a CAR T-cell therapy in heavily pretreated patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma,” first author Tanya Siddiqi, MD, associate professor in the division of lymphoma, City of Hope National Medical Center, Duarte, Calif., said in a press statement in connection with her presentation at the annual meeting of the American Society of Clinical Oncology.

“The durable complete responses observed with liso-cel in the TRANSCEND CLL 004 trial are remarkable and represent a major step in bringing a personalized, T cell–based treatment approach delivered as a one-time infusion into clinical practice for a complex and historically incurable disease,” she said.

Real-world evidence shows that patients with CLL or SLL who have relapsed or are refractory to treatment with BTKi therapy can have progressively worse outcomes. Moreover, with few other treatment options, research shows that the median time from dual discontinuation of BTKi and venetoclax to subsequent treatment failure or death is just 5.6 months.

“We are seeing a subset of patients now who are progressing on BTK inhibitors and venetoclax, and there is a high, unmet medical need for new, more effective treatments in this patient population,” Dr. Siddiqi said.

With liso-cel showing efficacy in the treatment of large B-cell lymphoma and receiving approval from the Food and Drug Administration for the indication, the multicenter TRANSCEND CLL 004 trial was launched to investigate the therapy’s effects in r/r CLL/SLL.

In a safety set of 117 patients with r/r CLL or SLL who received at least two prior lines of therapy, including a BTKi, patients received a single target dose of either 50 (n=9) or 100 × 106 (n = 87) CAR-positive T cells.

The primary efficacy analysis set included 49 patients who were treated with the target dose of 100 x 10⁶ CAR-positive viable T cells of liso-cel.

With a median on-study follow-up of 21.1 months, the primary endpoint of a complete response (CR) and complete response was achieved among 18.4% (n = 9; P = .0006).

Among patients achieving a complete response, no disease progression or deaths were reported, with a median duration of response that was not reached.

The undetectable minimal residual disease (MRD) rate was 63.3% in blood and 59.2% in bone marrow, which was associated with progression-free survival.

The overall response rate was 42.9%, which was not statistically significant, and the median duration of an objective response was 35.3 months (95% confidence interval, 11.01 to not reached).

The median time to first response was 1.2 months, and the median time to first complete response was 3.0 months.

The results were consistent in the broader safety set of 117 patients, including those who were heavily pretreated with a median of five prior lines of therapy (range, 2-12) and high-risk disease, with a CR rate of 18.4%.

In terms of safety, no new safety signals were observed, and the treatment’s safety profile was manageable, the authors noted.

Cytokine release syndrome (CRS), common with CAR T-cell therapy, occurred in 85% of patients; however, most cases were low grade; 9% of cases were grade 3, and there were no grade 4 or 5 cases.

Neurologic events occurred among 45%, including grade 3 in 17.9% and grade 4 in 0.9%, with no cases of grade 5.

For treatment of the CRS, 69.2% of patients received tocilizumab and/or corticosteroids for the cases of CRS and neurological events.

Of 51 deaths that occurred while on the study, 43 occurred following liso-cel infusion, including 5 caused by treatment-emergent adverse events occurring within 90 days of liso-cel infusion.

One death was determined to be related to liso-cel, involving macrophage activation syndrome–hemophagocytic lymphohistiocytosis.

“The safety profile was manageable, with low rates of grade 3 or higher CRS and neurotoxicity,” Dr. Siddiqi said.

She noted that, as encouraging as the results are, work should continue regarding further improving survival for patients.

“We need to look at this population more closely to see how we can make it even better for them,” she said in her talk.

For instance, “do we need to add maintenance, or do we need to do something else with CAR T therapy? Because one shot of CAR T is buying them a lot of time – 6 or 12 months of progression-free survival, but maybe we can make it even better.”

Dr. Siddiqi noted that she has “a lot of patients” who received CAR T-cell therapy who have not progressed or relapsed after as long as 4 years.

“I also have some patients who did relapse at 3 or 3 and 1/2 years, but everybody is so thankful for having that time of several years without any treatment; without the need for continuous therapy or continuous doctors’ visits. It is actually priceless,” she said.
 

Largest data set to date

Commenting on the study, Jakub Svoboda, MD, agreed that the findings suggest an important role of liso-cel among the growing numbers of patients who progress despite standard therapies.

“This is an important study and the [results] are very relevant as there is a growing population of patients with CLL/SLL who stopped responding to both BTKi and venetoclax and have limited options,” Dr. Svoboda, a medical oncologist at Penn Medicine, and associate professor of medicine at the Hospital of the University of Pennsylvania, both in Philadelphia, said in an interview.

“Many of my CLL/SLL patients benefited from BTK inhibitors and venetoclax for years, but it is clear that these are not curative agents, and ultimately our patients need other effective therapeutic options,” he said. “We have seen reports of smaller single-site studies with different anti-CD19 CAR T-cell products used in CLL/SLL in the past, but this multisite study using liso-cel represents the largest data set in over 100 patients with median follow-up of 21 months.”

Liso-cel, like other CAR T-cell treatments – which are derived from patients’ own cells that are then reengineered and delivered via a one-time infusion – has a 4-1BB costimulatory domain. This has the effect of enhancing the expansion and persistence of the CAR T cells.

Significantly, the study establishes that CAR T-cell manufacturing in CLL/SLL patients is feasible on a large scale, “which is important, considering the unique T-lymphocyte biology in CLL/SLL,” Dr. Svoboda remarked.

In terms of efficacy, “I have been mostly impressed by the high degree of undetectable minimal residual disease and the duration of response in the cohort of patients who previously failed both BTKi and venetoclax,” he added. “While there are a few agents used or being developed for patients failing both BTKi and venetoclax, it appears that CAR T-cell therapy has the unique potential to achieve long-term remissions in a subset of these patients.”

Discussant Carolyn Owen, MD, an associate professor in the division of hematology and hematological malignancies, University of Calgary (Alta.), and hematologist at the Tom Baker Cancer Centre, also in Calgary, also expressed enthusiasm over the encouraging results.

“The results of this study are very exciting,” she said during her discussion in the session.

“What is really important is that, even though this may be a small proportion of all of the patients, if we start offering this therapy a little bit earlier, and don’t wait for people to become completely refractory, we could increase the proportion of patients who are [not relapsing].”

Furthermore, “what’s most groundbreaking about this study is that patients could indeed have a really durable remission,” Dr. Owen added. “Hopefully not relapsing even beyond this 20-month follow up, which we haven’t seen with any of our other therapies.”

The results were also published in The Lancet.

The study was sponsored by Juno Therapeutics. Dr. Siddiqi disclosed relationships with Acerta Pharma, Ascentage Pharma, AstraZeneca, BeiGene, Bristol-Myers Squibb/Sanofi, Celgene, Juno Therapeutics, Kite, Oncternal Therapeutics, Pharmacyclics, and TG Therapeutics. Dr. Svoboda reported ties with Bristol-Myers Squibb. Dr. Owen disclosed relationships with Janssen, AstraZeneca, Roche Canada, AbbVie, Novartis Canada Pharmaceuticals, BeiGene, Merck, Incyte, and Seagen.

The CD19-directed chimeric antigen receptor (CAR) T-cell therapy lisocabtagene maraleucel (liso-cel, Bristol-Myers Squibb), showed efficacy in achieving complete responses among patients with relapsed or refractory chronic lymphocytic leukemia (r/r CLL) or small lymphocytic lymphoma (SLL), after treatment with a Bruton kinase inhibitor (BTKi) and BCL2 inhibitor.

The phase 1/2 TRANSCEND CLL 004 trial represents “the first pivotal multicenter trial to evaluate a CAR T-cell therapy in heavily pretreated patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma,” first author Tanya Siddiqi, MD, associate professor in the division of lymphoma, City of Hope National Medical Center, Duarte, Calif., said in a press statement in connection with her presentation at the annual meeting of the American Society of Clinical Oncology.

“The durable complete responses observed with liso-cel in the TRANSCEND CLL 004 trial are remarkable and represent a major step in bringing a personalized, T cell–based treatment approach delivered as a one-time infusion into clinical practice for a complex and historically incurable disease,” she said.

Real-world evidence shows that patients with CLL or SLL who have relapsed or are refractory to treatment with BTKi therapy can have progressively worse outcomes. Moreover, with few other treatment options, research shows that the median time from dual discontinuation of BTKi and venetoclax to subsequent treatment failure or death is just 5.6 months.

“We are seeing a subset of patients now who are progressing on BTK inhibitors and venetoclax, and there is a high, unmet medical need for new, more effective treatments in this patient population,” Dr. Siddiqi said.

With liso-cel showing efficacy in the treatment of large B-cell lymphoma and receiving approval from the Food and Drug Administration for the indication, the multicenter TRANSCEND CLL 004 trial was launched to investigate the therapy’s effects in r/r CLL/SLL.

In a safety set of 117 patients with r/r CLL or SLL who received at least two prior lines of therapy, including a BTKi, patients received a single target dose of either 50 (n=9) or 100 × 106 (n = 87) CAR-positive T cells.

The primary efficacy analysis set included 49 patients who were treated with the target dose of 100 x 10⁶ CAR-positive viable T cells of liso-cel.

With a median on-study follow-up of 21.1 months, the primary endpoint of a complete response (CR) and complete response was achieved among 18.4% (n = 9; P = .0006).

Among patients achieving a complete response, no disease progression or deaths were reported, with a median duration of response that was not reached.

The undetectable minimal residual disease (MRD) rate was 63.3% in blood and 59.2% in bone marrow, which was associated with progression-free survival.

The overall response rate was 42.9%, which was not statistically significant, and the median duration of an objective response was 35.3 months (95% confidence interval, 11.01 to not reached).

The median time to first response was 1.2 months, and the median time to first complete response was 3.0 months.

The results were consistent in the broader safety set of 117 patients, including those who were heavily pretreated with a median of five prior lines of therapy (range, 2-12) and high-risk disease, with a CR rate of 18.4%.

In terms of safety, no new safety signals were observed, and the treatment’s safety profile was manageable, the authors noted.

Cytokine release syndrome (CRS), common with CAR T-cell therapy, occurred in 85% of patients; however, most cases were low grade; 9% of cases were grade 3, and there were no grade 4 or 5 cases.

Neurologic events occurred among 45%, including grade 3 in 17.9% and grade 4 in 0.9%, with no cases of grade 5.

For treatment of the CRS, 69.2% of patients received tocilizumab and/or corticosteroids for the cases of CRS and neurological events.

Of 51 deaths that occurred while on the study, 43 occurred following liso-cel infusion, including 5 caused by treatment-emergent adverse events occurring within 90 days of liso-cel infusion.

One death was determined to be related to liso-cel, involving macrophage activation syndrome–hemophagocytic lymphohistiocytosis.

“The safety profile was manageable, with low rates of grade 3 or higher CRS and neurotoxicity,” Dr. Siddiqi said.

She noted that, as encouraging as the results are, work should continue regarding further improving survival for patients.

“We need to look at this population more closely to see how we can make it even better for them,” she said in her talk.

For instance, “do we need to add maintenance, or do we need to do something else with CAR T therapy? Because one shot of CAR T is buying them a lot of time – 6 or 12 months of progression-free survival, but maybe we can make it even better.”

Dr. Siddiqi noted that she has “a lot of patients” who received CAR T-cell therapy who have not progressed or relapsed after as long as 4 years.

“I also have some patients who did relapse at 3 or 3 and 1/2 years, but everybody is so thankful for having that time of several years without any treatment; without the need for continuous therapy or continuous doctors’ visits. It is actually priceless,” she said.
 

Largest data set to date

Commenting on the study, Jakub Svoboda, MD, agreed that the findings suggest an important role of liso-cel among the growing numbers of patients who progress despite standard therapies.

“This is an important study and the [results] are very relevant as there is a growing population of patients with CLL/SLL who stopped responding to both BTKi and venetoclax and have limited options,” Dr. Svoboda, a medical oncologist at Penn Medicine, and associate professor of medicine at the Hospital of the University of Pennsylvania, both in Philadelphia, said in an interview.

“Many of my CLL/SLL patients benefited from BTK inhibitors and venetoclax for years, but it is clear that these are not curative agents, and ultimately our patients need other effective therapeutic options,” he said. “We have seen reports of smaller single-site studies with different anti-CD19 CAR T-cell products used in CLL/SLL in the past, but this multisite study using liso-cel represents the largest data set in over 100 patients with median follow-up of 21 months.”

Liso-cel, like other CAR T-cell treatments – which are derived from patients’ own cells that are then reengineered and delivered via a one-time infusion – has a 4-1BB costimulatory domain. This has the effect of enhancing the expansion and persistence of the CAR T cells.

Significantly, the study establishes that CAR T-cell manufacturing in CLL/SLL patients is feasible on a large scale, “which is important, considering the unique T-lymphocyte biology in CLL/SLL,” Dr. Svoboda remarked.

In terms of efficacy, “I have been mostly impressed by the high degree of undetectable minimal residual disease and the duration of response in the cohort of patients who previously failed both BTKi and venetoclax,” he added. “While there are a few agents used or being developed for patients failing both BTKi and venetoclax, it appears that CAR T-cell therapy has the unique potential to achieve long-term remissions in a subset of these patients.”

Discussant Carolyn Owen, MD, an associate professor in the division of hematology and hematological malignancies, University of Calgary (Alta.), and hematologist at the Tom Baker Cancer Centre, also in Calgary, also expressed enthusiasm over the encouraging results.

“The results of this study are very exciting,” she said during her discussion in the session.

“What is really important is that, even though this may be a small proportion of all of the patients, if we start offering this therapy a little bit earlier, and don’t wait for people to become completely refractory, we could increase the proportion of patients who are [not relapsing].”

Furthermore, “what’s most groundbreaking about this study is that patients could indeed have a really durable remission,” Dr. Owen added. “Hopefully not relapsing even beyond this 20-month follow up, which we haven’t seen with any of our other therapies.”

The results were also published in The Lancet.

The study was sponsored by Juno Therapeutics. Dr. Siddiqi disclosed relationships with Acerta Pharma, Ascentage Pharma, AstraZeneca, BeiGene, Bristol-Myers Squibb/Sanofi, Celgene, Juno Therapeutics, Kite, Oncternal Therapeutics, Pharmacyclics, and TG Therapeutics. Dr. Svoboda reported ties with Bristol-Myers Squibb. Dr. Owen disclosed relationships with Janssen, AstraZeneca, Roche Canada, AbbVie, Novartis Canada Pharmaceuticals, BeiGene, Merck, Incyte, and Seagen.

The CD19-directed chimeric antigen receptor (CAR) T-cell therapy lisocabtagene maraleucel (liso-cel, Bristol-Myers Squibb), showed efficacy in achieving complete responses among patients with relapsed or refractory chronic lymphocytic leukemia (r/r CLL) or small lymphocytic lymphoma (SLL), after treatment with a Bruton kinase inhibitor (BTKi) and BCL2 inhibitor.

The phase 1/2 TRANSCEND CLL 004 trial represents “the first pivotal multicenter trial to evaluate a CAR T-cell therapy in heavily pretreated patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma,” first author Tanya Siddiqi, MD, associate professor in the division of lymphoma, City of Hope National Medical Center, Duarte, Calif., said in a press statement in connection with her presentation at the annual meeting of the American Society of Clinical Oncology.

“The durable complete responses observed with liso-cel in the TRANSCEND CLL 004 trial are remarkable and represent a major step in bringing a personalized, T cell–based treatment approach delivered as a one-time infusion into clinical practice for a complex and historically incurable disease,” she said.

Real-world evidence shows that patients with CLL or SLL who have relapsed or are refractory to treatment with BTKi therapy can have progressively worse outcomes. Moreover, with few other treatment options, research shows that the median time from dual discontinuation of BTKi and venetoclax to subsequent treatment failure or death is just 5.6 months.

“We are seeing a subset of patients now who are progressing on BTK inhibitors and venetoclax, and there is a high, unmet medical need for new, more effective treatments in this patient population,” Dr. Siddiqi said.

With liso-cel showing efficacy in the treatment of large B-cell lymphoma and receiving approval from the Food and Drug Administration for the indication, the multicenter TRANSCEND CLL 004 trial was launched to investigate the therapy’s effects in r/r CLL/SLL.

In a safety set of 117 patients with r/r CLL or SLL who received at least two prior lines of therapy, including a BTKi, patients received a single target dose of either 50 (n=9) or 100 × 106 (n = 87) CAR-positive T cells.

The primary efficacy analysis set included 49 patients who were treated with the target dose of 100 x 10⁶ CAR-positive viable T cells of liso-cel.

With a median on-study follow-up of 21.1 months, the primary endpoint of a complete response (CR) and complete response was achieved among 18.4% (n = 9; P = .0006).

Among patients achieving a complete response, no disease progression or deaths were reported, with a median duration of response that was not reached.

The undetectable minimal residual disease (MRD) rate was 63.3% in blood and 59.2% in bone marrow, which was associated with progression-free survival.

The overall response rate was 42.9%, which was not statistically significant, and the median duration of an objective response was 35.3 months (95% confidence interval, 11.01 to not reached).

The median time to first response was 1.2 months, and the median time to first complete response was 3.0 months.

The results were consistent in the broader safety set of 117 patients, including those who were heavily pretreated with a median of five prior lines of therapy (range, 2-12) and high-risk disease, with a CR rate of 18.4%.

In terms of safety, no new safety signals were observed, and the treatment’s safety profile was manageable, the authors noted.

Cytokine release syndrome (CRS), common with CAR T-cell therapy, occurred in 85% of patients; however, most cases were low grade; 9% of cases were grade 3, and there were no grade 4 or 5 cases.

Neurologic events occurred among 45%, including grade 3 in 17.9% and grade 4 in 0.9%, with no cases of grade 5.

For treatment of the CRS, 69.2% of patients received tocilizumab and/or corticosteroids for the cases of CRS and neurological events.

Of 51 deaths that occurred while on the study, 43 occurred following liso-cel infusion, including 5 caused by treatment-emergent adverse events occurring within 90 days of liso-cel infusion.

One death was determined to be related to liso-cel, involving macrophage activation syndrome–hemophagocytic lymphohistiocytosis.

“The safety profile was manageable, with low rates of grade 3 or higher CRS and neurotoxicity,” Dr. Siddiqi said.

She noted that, as encouraging as the results are, work should continue regarding further improving survival for patients.

“We need to look at this population more closely to see how we can make it even better for them,” she said in her talk.

For instance, “do we need to add maintenance, or do we need to do something else with CAR T therapy? Because one shot of CAR T is buying them a lot of time – 6 or 12 months of progression-free survival, but maybe we can make it even better.”

Dr. Siddiqi noted that she has “a lot of patients” who received CAR T-cell therapy who have not progressed or relapsed after as long as 4 years.

“I also have some patients who did relapse at 3 or 3 and 1/2 years, but everybody is so thankful for having that time of several years without any treatment; without the need for continuous therapy or continuous doctors’ visits. It is actually priceless,” she said.
 

Largest data set to date

Commenting on the study, Jakub Svoboda, MD, agreed that the findings suggest an important role of liso-cel among the growing numbers of patients who progress despite standard therapies.

“This is an important study and the [results] are very relevant as there is a growing population of patients with CLL/SLL who stopped responding to both BTKi and venetoclax and have limited options,” Dr. Svoboda, a medical oncologist at Penn Medicine, and associate professor of medicine at the Hospital of the University of Pennsylvania, both in Philadelphia, said in an interview.

“Many of my CLL/SLL patients benefited from BTK inhibitors and venetoclax for years, but it is clear that these are not curative agents, and ultimately our patients need other effective therapeutic options,” he said. “We have seen reports of smaller single-site studies with different anti-CD19 CAR T-cell products used in CLL/SLL in the past, but this multisite study using liso-cel represents the largest data set in over 100 patients with median follow-up of 21 months.”

Liso-cel, like other CAR T-cell treatments – which are derived from patients’ own cells that are then reengineered and delivered via a one-time infusion – has a 4-1BB costimulatory domain. This has the effect of enhancing the expansion and persistence of the CAR T cells.

Significantly, the study establishes that CAR T-cell manufacturing in CLL/SLL patients is feasible on a large scale, “which is important, considering the unique T-lymphocyte biology in CLL/SLL,” Dr. Svoboda remarked.

In terms of efficacy, “I have been mostly impressed by the high degree of undetectable minimal residual disease and the duration of response in the cohort of patients who previously failed both BTKi and venetoclax,” he added. “While there are a few agents used or being developed for patients failing both BTKi and venetoclax, it appears that CAR T-cell therapy has the unique potential to achieve long-term remissions in a subset of these patients.”

Discussant Carolyn Owen, MD, an associate professor in the division of hematology and hematological malignancies, University of Calgary (Alta.), and hematologist at the Tom Baker Cancer Centre, also in Calgary, also expressed enthusiasm over the encouraging results.

“The results of this study are very exciting,” she said during her discussion in the session.

“What is really important is that, even though this may be a small proportion of all of the patients, if we start offering this therapy a little bit earlier, and don’t wait for people to become completely refractory, we could increase the proportion of patients who are [not relapsing].”

Furthermore, “what’s most groundbreaking about this study is that patients could indeed have a really durable remission,” Dr. Owen added. “Hopefully not relapsing even beyond this 20-month follow up, which we haven’t seen with any of our other therapies.”

The results were also published in The Lancet.

The study was sponsored by Juno Therapeutics. Dr. Siddiqi disclosed relationships with Acerta Pharma, Ascentage Pharma, AstraZeneca, BeiGene, Bristol-Myers Squibb/Sanofi, Celgene, Juno Therapeutics, Kite, Oncternal Therapeutics, Pharmacyclics, and TG Therapeutics. Dr. Svoboda reported ties with Bristol-Myers Squibb. Dr. Owen disclosed relationships with Janssen, AstraZeneca, Roche Canada, AbbVie, Novartis Canada Pharmaceuticals, BeiGene, Merck, Incyte, and Seagen.

For patients with primary mediastinal B-cell lymphoma (PMBCL) who achieved a complete metabolic response after immunochemotherapy, radiation therapy may be safely omitted without heightening their risks of relapse or disease progression – thereby sparing them the toxicity and costs of this additional treatment.

“This study is the largest prospective study of PMBCL ever conducted,” said first author Emanuele Zucca, MD, consultant and head of the lymphoma unit at the Oncology Institute of Southern Switzerland in Bellinzona. Dr. Zucca presented the findings at the annual meeting of the American Society of Clinical Oncology (ASCO).

The results of the research underscore that “mediastinal radiation therapy in patients with complete remission after frontline immunochemotherapy can be safely omitted,” he said.

While PMBCL has a relatively low incidence, representing fewer than 5% of cases of non-Hodgkin lymphoma, the cancer is over-represented in young White women between approximately 30 and 40 years of age, and is a notably aggressive form of diffuse large B-cell lymphoma.

However, in patients who rapidly achieve remission with dose-intensive immunochemotherapy, the prognosis is good.

In such cases, the use of mediastinal radiation therapy has been seen as a measure to further consolidate the immunochemotherapy response, but the additional treatment comes at the cost of an increased risk of second malignancies, as well as coronary or valvular heart disease.

Meanwhile, in recent decades promising data has shown that aggressive chemoimmunotherapy regimens alone, such as DA-EPOCH-R (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) can be enough for patients achieving a complete remission, while novel approaches such as checkpoint inhibitors and CAR T-cell therapy further show benefits in patients with lymphoma that relapses after treatment.

With ongoing controversy over whether to include the added radiation therapy among patients with a complete metabolic response, Dr. Zucca and his colleagues conducted the IELSG37 international study, enrolling 545 patients from 74 centers in 13 countries, including 336 women, with newly diagnosed PMBCL.

The patients were treated with induction chemoimmunotherapy with rituximab and anthracycline-based therapy based on local practice, and response assessed among of 530 of the 545 patients showed that 268 (50.6%) achieved a complete metabolic response.

Those patients were then randomized to either observation (n = 132) or consolidation radiation therapy (30 Gy; n = 136). The characteristics between the two groups were similar, with a mean age of 35.5, and about 65% female.

With a median follow-up of 63 months (range, 48-60 months), the primary endpoint of progression-free survival at 30 months was not significantly different between the observation arm (98.5%) and radiation therapy arm (96.2%; P = .278).

After adjustment for factors including sex, chemotherapy, country, and positron emission tomography (PET) response score, the estimated relative effect of radiotherapy versus observation was a hazard ratio of 0.68, and the absolute risk reduction associated with radiotherapy at 30 months was 1.2% after adjustment.

The number needed to treat is high, at 126.3 after stratification, and the 5-year overall survival was excellent in both arms, at 99%.

“What this tells us is that treatment with radiation therapy in well over 100 patients is needed just to avoid a single recurrence,” Dr. Zucca explained.

Overall survival after 3 years was excellent and identical in both arms, at about 99%.

To date, three severe cardiac events and three second cancers have been recorded in the study, all occurring among patients randomized to receive radiation therapy.

Dr. Zucca noted that longer follow-up is needed to better examine late toxicities.

“The long-term toxicities of mediastinal radiotherapy are well documented, particularly second breast, thyroid, and lung cancers and increased risk of coronary or valvular heart disease, in a patient group dominated by young adults,” Dr. Zucca said in a press statement.

“This study shows chemoimmunotherapy alone is an effective treatment for primary mediastinal B-cell lymphoma and strongly supports omitting radiotherapy without impacting chances of cure.”

Commenting on the study, Corey W. Speers, MD, PhD, assistant professor, radiation oncology, department of surgery, University of Michigan Hospital, Ann Arbor, said the findings have important clinical implications.

“We all should be encouraged by the low rates in this trial, which are lower than expected,” Dr. Speers said in a press briefing.

In further comments, he added that “these results will inform and likely change clinical practice.”

Dr. Speers said the study is notable for being the first of its kind.

“This clinical question has not previously been directly addressed, and this is the first study to do so,” he said.

“With more effective systemic therapies, many patients have their lymphoma disappear with early aggressive treatment, and although radiation is very effective at treating lymphoma, it has not been clear if it is needed in these patients that have an early rapid response to systemic therapy before starting radiation,” Dr. Speers explained.

“We have struggled as oncologists to know whether omitting this effective radiotherapy would compromise outcomes, and thus many were inclined to continue offering it to patients, even with the great early response. This study helps answer this critical question,” he said.

The results add reassuring evidence, buttressing efforts to avoid unnecessary interventions that may provide little or no benefit, Dr. Speers added.

“We are now in an era of ‘less being more’ as we seek ways to provide optimal quality and quantity of life to patients with cancer and their families, and this is just another example of the tremendous progress being made.”

Further commenting on the study at the press briefing, Julie R. Gralow, MD, ASCO chief medical officer and executive vice president, said the research supports ASCO’s ongoing efforts to reduce the toxicities of cancer treatment.

“Our ASCO vision is a world where cancer is either prevented or cured, and every patient is cured – and every survivor is healthy, and that part about every survivor being healthy is what we’re working on here [in this study],” Dr. Gralow said.

The study was funded by the Swiss Cancer League and Cancer Research UK, with partial support from the Swiss National Science Foundation. Dr. Zucca reported relationships with AstraZeneca, Beigene, Celgene, Incyte, Janssen, Merck, Roche, Celltrion Healthcare, Kite, and Abbvie. Dr. Speers disclosed his coinvention of technology that assesses radiosensitivity and predicts benefits from adjutant radiotherapy.

For patients with primary mediastinal B-cell lymphoma (PMBCL) who achieved a complete metabolic response after immunochemotherapy, radiation therapy may be safely omitted without heightening their risks of relapse or disease progression – thereby sparing them the toxicity and costs of this additional treatment.

“This study is the largest prospective study of PMBCL ever conducted,” said first author Emanuele Zucca, MD, consultant and head of the lymphoma unit at the Oncology Institute of Southern Switzerland in Bellinzona. Dr. Zucca presented the findings at the annual meeting of the American Society of Clinical Oncology (ASCO).

The results of the research underscore that “mediastinal radiation therapy in patients with complete remission after frontline immunochemotherapy can be safely omitted,” he said.

While PMBCL has a relatively low incidence, representing fewer than 5% of cases of non-Hodgkin lymphoma, the cancer is over-represented in young White women between approximately 30 and 40 years of age, and is a notably aggressive form of diffuse large B-cell lymphoma.

However, in patients who rapidly achieve remission with dose-intensive immunochemotherapy, the prognosis is good.

In such cases, the use of mediastinal radiation therapy has been seen as a measure to further consolidate the immunochemotherapy response, but the additional treatment comes at the cost of an increased risk of second malignancies, as well as coronary or valvular heart disease.

Meanwhile, in recent decades promising data has shown that aggressive chemoimmunotherapy regimens alone, such as DA-EPOCH-R (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) can be enough for patients achieving a complete remission, while novel approaches such as checkpoint inhibitors and CAR T-cell therapy further show benefits in patients with lymphoma that relapses after treatment.

With ongoing controversy over whether to include the added radiation therapy among patients with a complete metabolic response, Dr. Zucca and his colleagues conducted the IELSG37 international study, enrolling 545 patients from 74 centers in 13 countries, including 336 women, with newly diagnosed PMBCL.

The patients were treated with induction chemoimmunotherapy with rituximab and anthracycline-based therapy based on local practice, and response assessed among of 530 of the 545 patients showed that 268 (50.6%) achieved a complete metabolic response.

Those patients were then randomized to either observation (n = 132) or consolidation radiation therapy (30 Gy; n = 136). The characteristics between the two groups were similar, with a mean age of 35.5, and about 65% female.

With a median follow-up of 63 months (range, 48-60 months), the primary endpoint of progression-free survival at 30 months was not significantly different between the observation arm (98.5%) and radiation therapy arm (96.2%; P = .278).

After adjustment for factors including sex, chemotherapy, country, and positron emission tomography (PET) response score, the estimated relative effect of radiotherapy versus observation was a hazard ratio of 0.68, and the absolute risk reduction associated with radiotherapy at 30 months was 1.2% after adjustment.

The number needed to treat is high, at 126.3 after stratification, and the 5-year overall survival was excellent in both arms, at 99%.

“What this tells us is that treatment with radiation therapy in well over 100 patients is needed just to avoid a single recurrence,” Dr. Zucca explained.

Overall survival after 3 years was excellent and identical in both arms, at about 99%.

To date, three severe cardiac events and three second cancers have been recorded in the study, all occurring among patients randomized to receive radiation therapy.

Dr. Zucca noted that longer follow-up is needed to better examine late toxicities.

“The long-term toxicities of mediastinal radiotherapy are well documented, particularly second breast, thyroid, and lung cancers and increased risk of coronary or valvular heart disease, in a patient group dominated by young adults,” Dr. Zucca said in a press statement.

“This study shows chemoimmunotherapy alone is an effective treatment for primary mediastinal B-cell lymphoma and strongly supports omitting radiotherapy without impacting chances of cure.”

Commenting on the study, Corey W. Speers, MD, PhD, assistant professor, radiation oncology, department of surgery, University of Michigan Hospital, Ann Arbor, said the findings have important clinical implications.

“We all should be encouraged by the low rates in this trial, which are lower than expected,” Dr. Speers said in a press briefing.

In further comments, he added that “these results will inform and likely change clinical practice.”

Dr. Speers said the study is notable for being the first of its kind.

“This clinical question has not previously been directly addressed, and this is the first study to do so,” he said.

“With more effective systemic therapies, many patients have their lymphoma disappear with early aggressive treatment, and although radiation is very effective at treating lymphoma, it has not been clear if it is needed in these patients that have an early rapid response to systemic therapy before starting radiation,” Dr. Speers explained.

“We have struggled as oncologists to know whether omitting this effective radiotherapy would compromise outcomes, and thus many were inclined to continue offering it to patients, even with the great early response. This study helps answer this critical question,” he said.

The results add reassuring evidence, buttressing efforts to avoid unnecessary interventions that may provide little or no benefit, Dr. Speers added.

“We are now in an era of ‘less being more’ as we seek ways to provide optimal quality and quantity of life to patients with cancer and their families, and this is just another example of the tremendous progress being made.”

Further commenting on the study at the press briefing, Julie R. Gralow, MD, ASCO chief medical officer and executive vice president, said the research supports ASCO’s ongoing efforts to reduce the toxicities of cancer treatment.

“Our ASCO vision is a world where cancer is either prevented or cured, and every patient is cured – and every survivor is healthy, and that part about every survivor being healthy is what we’re working on here [in this study],” Dr. Gralow said.

The study was funded by the Swiss Cancer League and Cancer Research UK, with partial support from the Swiss National Science Foundation. Dr. Zucca reported relationships with AstraZeneca, Beigene, Celgene, Incyte, Janssen, Merck, Roche, Celltrion Healthcare, Kite, and Abbvie. Dr. Speers disclosed his coinvention of technology that assesses radiosensitivity and predicts benefits from adjutant radiotherapy.

For patients with primary mediastinal B-cell lymphoma (PMBCL) who achieved a complete metabolic response after immunochemotherapy, radiation therapy may be safely omitted without heightening their risks of relapse or disease progression – thereby sparing them the toxicity and costs of this additional treatment.

“This study is the largest prospective study of PMBCL ever conducted,” said first author Emanuele Zucca, MD, consultant and head of the lymphoma unit at the Oncology Institute of Southern Switzerland in Bellinzona. Dr. Zucca presented the findings at the annual meeting of the American Society of Clinical Oncology (ASCO).

The results of the research underscore that “mediastinal radiation therapy in patients with complete remission after frontline immunochemotherapy can be safely omitted,” he said.

While PMBCL has a relatively low incidence, representing fewer than 5% of cases of non-Hodgkin lymphoma, the cancer is over-represented in young White women between approximately 30 and 40 years of age, and is a notably aggressive form of diffuse large B-cell lymphoma.

However, in patients who rapidly achieve remission with dose-intensive immunochemotherapy, the prognosis is good.

In such cases, the use of mediastinal radiation therapy has been seen as a measure to further consolidate the immunochemotherapy response, but the additional treatment comes at the cost of an increased risk of second malignancies, as well as coronary or valvular heart disease.

Meanwhile, in recent decades promising data has shown that aggressive chemoimmunotherapy regimens alone, such as DA-EPOCH-R (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) can be enough for patients achieving a complete remission, while novel approaches such as checkpoint inhibitors and CAR T-cell therapy further show benefits in patients with lymphoma that relapses after treatment.

With ongoing controversy over whether to include the added radiation therapy among patients with a complete metabolic response, Dr. Zucca and his colleagues conducted the IELSG37 international study, enrolling 545 patients from 74 centers in 13 countries, including 336 women, with newly diagnosed PMBCL.

The patients were treated with induction chemoimmunotherapy with rituximab and anthracycline-based therapy based on local practice, and response assessed among of 530 of the 545 patients showed that 268 (50.6%) achieved a complete metabolic response.

Those patients were then randomized to either observation (n = 132) or consolidation radiation therapy (30 Gy; n = 136). The characteristics between the two groups were similar, with a mean age of 35.5, and about 65% female.

With a median follow-up of 63 months (range, 48-60 months), the primary endpoint of progression-free survival at 30 months was not significantly different between the observation arm (98.5%) and radiation therapy arm (96.2%; P = .278).

After adjustment for factors including sex, chemotherapy, country, and positron emission tomography (PET) response score, the estimated relative effect of radiotherapy versus observation was a hazard ratio of 0.68, and the absolute risk reduction associated with radiotherapy at 30 months was 1.2% after adjustment.

The number needed to treat is high, at 126.3 after stratification, and the 5-year overall survival was excellent in both arms, at 99%.

“What this tells us is that treatment with radiation therapy in well over 100 patients is needed just to avoid a single recurrence,” Dr. Zucca explained.

Overall survival after 3 years was excellent and identical in both arms, at about 99%.

To date, three severe cardiac events and three second cancers have been recorded in the study, all occurring among patients randomized to receive radiation therapy.

Dr. Zucca noted that longer follow-up is needed to better examine late toxicities.

“The long-term toxicities of mediastinal radiotherapy are well documented, particularly second breast, thyroid, and lung cancers and increased risk of coronary or valvular heart disease, in a patient group dominated by young adults,” Dr. Zucca said in a press statement.

“This study shows chemoimmunotherapy alone is an effective treatment for primary mediastinal B-cell lymphoma and strongly supports omitting radiotherapy without impacting chances of cure.”

Commenting on the study, Corey W. Speers, MD, PhD, assistant professor, radiation oncology, department of surgery, University of Michigan Hospital, Ann Arbor, said the findings have important clinical implications.

“We all should be encouraged by the low rates in this trial, which are lower than expected,” Dr. Speers said in a press briefing.

In further comments, he added that “these results will inform and likely change clinical practice.”

Dr. Speers said the study is notable for being the first of its kind.

“This clinical question has not previously been directly addressed, and this is the first study to do so,” he said.

“With more effective systemic therapies, many patients have their lymphoma disappear with early aggressive treatment, and although radiation is very effective at treating lymphoma, it has not been clear if it is needed in these patients that have an early rapid response to systemic therapy before starting radiation,” Dr. Speers explained.

“We have struggled as oncologists to know whether omitting this effective radiotherapy would compromise outcomes, and thus many were inclined to continue offering it to patients, even with the great early response. This study helps answer this critical question,” he said.

The results add reassuring evidence, buttressing efforts to avoid unnecessary interventions that may provide little or no benefit, Dr. Speers added.

“We are now in an era of ‘less being more’ as we seek ways to provide optimal quality and quantity of life to patients with cancer and their families, and this is just another example of the tremendous progress being made.”

Further commenting on the study at the press briefing, Julie R. Gralow, MD, ASCO chief medical officer and executive vice president, said the research supports ASCO’s ongoing efforts to reduce the toxicities of cancer treatment.

“Our ASCO vision is a world where cancer is either prevented or cured, and every patient is cured – and every survivor is healthy, and that part about every survivor being healthy is what we’re working on here [in this study],” Dr. Gralow said.

The study was funded by the Swiss Cancer League and Cancer Research UK, with partial support from the Swiss National Science Foundation. Dr. Zucca reported relationships with AstraZeneca, Beigene, Celgene, Incyte, Janssen, Merck, Roche, Celltrion Healthcare, Kite, and Abbvie. Dr. Speers disclosed his coinvention of technology that assesses radiosensitivity and predicts benefits from adjutant radiotherapy.

The number of cancer survivors who report functional limitation has more than doubled in 20 years, according to a research letter published in JAMA Oncology.

Vishal Patel, BS, a student at the Dell Medical School at The University of Texas at Austin, and colleagues identified 51,258 cancer survivors from the National Health Interview Survey, representing a weighted population of approximately 178.8 million from 1999 to 2018.

Most survivors were women (60.2%) and were at least 65 years old (55.4%). In 1999, 3.6 million weighted survivors reported functional limitation. In 2018, the number increased to 8.2 million, a 2.25-fold increase.

The number of survivors who reported no limitations also increased, but not by as much. That group grew 1.34-fold during the study period.

For context, “the 70% prevalence of functional limitation among survivors in 2018 is nearly twice that of the general population,” the authors wrote.
 

Patients surveyed on function

Functional limitation was defined as “self-reported difficulty performing any of 12 routine physical or social activities without assistance.” Examples of the activities included difficulty sitting for more than 2 hours, difficulty participating in social activities or difficulty pushing or pulling an object the size of a living room chair.

Over the 2 decades analyzed, the adjusted prevalence of functional limitation was highest among survivors of pancreatic cancer (80.3%) and lung cancer (76.5%). Prevalence was lowest for survivors of melanoma (62.2%), breast (61.8%) and prostate (59.5%) cancers.
 

Not just a result of living longer

Mr. Patel told this publication that one assumption people might make when they read these results is that people are just living longer with cancer and losing functional ability accordingly.

“But, in fact, we found that the youngest [– those less than 65 years–] actually contributed to this trend more than the oldest people, which means it’s not just [happening], because people are getting older,” he said.

Hispanic and Black individuals had disproportionately higher increases in functional limitation; percentage point increases over the 2 decades were 19.5 for Black people, 25.1 for Hispanic people and 12.5 for White people. There may be a couple of reasons for that, Mr. Patel noted.

Those who are Black or Hispanic tend to have less access to cancer survivorship care for reasons including insurance status and historic health care inequities, he noted.

“The other potential reason is that they have had less access to cancer care historically. And if, 20 years ago Black and Hispanic individuals didn’t have access to some chemotherapies, and now they do, maybe it’s the increased access to care that’s causing these functional limitations. Because chemotherapy can sometimes be very toxic. It may be sort of a catch-up toxicity,” he said.
 

Quality of life beyond survivorship

Mr. Patel said the results seem to call for building on improved survival rates by tracking and improving function.

“It’s good to celebrate that there are more survivors. But now that we can keep people alive longer, maybe we can shift gears to improving their quality of life,” he said.

The more-than-doubling of functional limitations over 2 decades “is a very sobering trend,” he noted, while pointing out that the functional limitations applied to 8 million people in the United States – people whose needs are not being met.

There’s no sign of the trend stopping, he continued. “We saw no downward trend, only an upward trend.”

Increasingly, including functionality as an endpoint in cancer trials, in addition to improvements in mortality, is one place to start, he added.

“Our findings suggest an urgent need for care teams to understand and address function, for researchers to evaluate function as a core outcome in trials, and for health systems and policy makers to reimagine survivorship care, recognizing the burden of cancer and its treatment on physical, psychosocial, and cognitive function,” the authors wrote in their paper. Limitations of the study include the potential for recall bias, lack of cancer staging or treatment information, and the subjective perception of function.

A coauthor reported personal fees from Astellas, AstraZeneca, AAA, Blue Earth, Janssen, Lantheus, Myovant, Myriad Genetics, Novartis, Telix, and Sanofi, as well as grants from Pfizer and Bayer during the conduct of the study. No other disclosures were reported.

The number of cancer survivors who report functional limitation has more than doubled in 20 years, according to a research letter published in JAMA Oncology.

Vishal Patel, BS, a student at the Dell Medical School at The University of Texas at Austin, and colleagues identified 51,258 cancer survivors from the National Health Interview Survey, representing a weighted population of approximately 178.8 million from 1999 to 2018.

Most survivors were women (60.2%) and were at least 65 years old (55.4%). In 1999, 3.6 million weighted survivors reported functional limitation. In 2018, the number increased to 8.2 million, a 2.25-fold increase.

The number of survivors who reported no limitations also increased, but not by as much. That group grew 1.34-fold during the study period.

For context, “the 70% prevalence of functional limitation among survivors in 2018 is nearly twice that of the general population,” the authors wrote.
 

Patients surveyed on function

Functional limitation was defined as “self-reported difficulty performing any of 12 routine physical or social activities without assistance.” Examples of the activities included difficulty sitting for more than 2 hours, difficulty participating in social activities or difficulty pushing or pulling an object the size of a living room chair.

Over the 2 decades analyzed, the adjusted prevalence of functional limitation was highest among survivors of pancreatic cancer (80.3%) and lung cancer (76.5%). Prevalence was lowest for survivors of melanoma (62.2%), breast (61.8%) and prostate (59.5%) cancers.
 

Not just a result of living longer

Mr. Patel told this publication that one assumption people might make when they read these results is that people are just living longer with cancer and losing functional ability accordingly.

“But, in fact, we found that the youngest [– those less than 65 years–] actually contributed to this trend more than the oldest people, which means it’s not just [happening], because people are getting older,” he said.

Hispanic and Black individuals had disproportionately higher increases in functional limitation; percentage point increases over the 2 decades were 19.5 for Black people, 25.1 for Hispanic people and 12.5 for White people. There may be a couple of reasons for that, Mr. Patel noted.

Those who are Black or Hispanic tend to have less access to cancer survivorship care for reasons including insurance status and historic health care inequities, he noted.

“The other potential reason is that they have had less access to cancer care historically. And if, 20 years ago Black and Hispanic individuals didn’t have access to some chemotherapies, and now they do, maybe it’s the increased access to care that’s causing these functional limitations. Because chemotherapy can sometimes be very toxic. It may be sort of a catch-up toxicity,” he said.
 

Quality of life beyond survivorship

Mr. Patel said the results seem to call for building on improved survival rates by tracking and improving function.

“It’s good to celebrate that there are more survivors. But now that we can keep people alive longer, maybe we can shift gears to improving their quality of life,” he said.

The more-than-doubling of functional limitations over 2 decades “is a very sobering trend,” he noted, while pointing out that the functional limitations applied to 8 million people in the United States – people whose needs are not being met.

There’s no sign of the trend stopping, he continued. “We saw no downward trend, only an upward trend.”

Increasingly, including functionality as an endpoint in cancer trials, in addition to improvements in mortality, is one place to start, he added.

“Our findings suggest an urgent need for care teams to understand and address function, for researchers to evaluate function as a core outcome in trials, and for health systems and policy makers to reimagine survivorship care, recognizing the burden of cancer and its treatment on physical, psychosocial, and cognitive function,” the authors wrote in their paper. Limitations of the study include the potential for recall bias, lack of cancer staging or treatment information, and the subjective perception of function.

A coauthor reported personal fees from Astellas, AstraZeneca, AAA, Blue Earth, Janssen, Lantheus, Myovant, Myriad Genetics, Novartis, Telix, and Sanofi, as well as grants from Pfizer and Bayer during the conduct of the study. No other disclosures were reported.

The number of cancer survivors who report functional limitation has more than doubled in 20 years, according to a research letter published in JAMA Oncology.

Vishal Patel, BS, a student at the Dell Medical School at The University of Texas at Austin, and colleagues identified 51,258 cancer survivors from the National Health Interview Survey, representing a weighted population of approximately 178.8 million from 1999 to 2018.

Most survivors were women (60.2%) and were at least 65 years old (55.4%). In 1999, 3.6 million weighted survivors reported functional limitation. In 2018, the number increased to 8.2 million, a 2.25-fold increase.

The number of survivors who reported no limitations also increased, but not by as much. That group grew 1.34-fold during the study period.

For context, “the 70% prevalence of functional limitation among survivors in 2018 is nearly twice that of the general population,” the authors wrote.
 

Patients surveyed on function

Functional limitation was defined as “self-reported difficulty performing any of 12 routine physical or social activities without assistance.” Examples of the activities included difficulty sitting for more than 2 hours, difficulty participating in social activities or difficulty pushing or pulling an object the size of a living room chair.

Over the 2 decades analyzed, the adjusted prevalence of functional limitation was highest among survivors of pancreatic cancer (80.3%) and lung cancer (76.5%). Prevalence was lowest for survivors of melanoma (62.2%), breast (61.8%) and prostate (59.5%) cancers.
 

Not just a result of living longer

Mr. Patel told this publication that one assumption people might make when they read these results is that people are just living longer with cancer and losing functional ability accordingly.

“But, in fact, we found that the youngest [– those less than 65 years–] actually contributed to this trend more than the oldest people, which means it’s not just [happening], because people are getting older,” he said.

Hispanic and Black individuals had disproportionately higher increases in functional limitation; percentage point increases over the 2 decades were 19.5 for Black people, 25.1 for Hispanic people and 12.5 for White people. There may be a couple of reasons for that, Mr. Patel noted.

Those who are Black or Hispanic tend to have less access to cancer survivorship care for reasons including insurance status and historic health care inequities, he noted.

“The other potential reason is that they have had less access to cancer care historically. And if, 20 years ago Black and Hispanic individuals didn’t have access to some chemotherapies, and now they do, maybe it’s the increased access to care that’s causing these functional limitations. Because chemotherapy can sometimes be very toxic. It may be sort of a catch-up toxicity,” he said.
 

Quality of life beyond survivorship

Mr. Patel said the results seem to call for building on improved survival rates by tracking and improving function.

“It’s good to celebrate that there are more survivors. But now that we can keep people alive longer, maybe we can shift gears to improving their quality of life,” he said.

The more-than-doubling of functional limitations over 2 decades “is a very sobering trend,” he noted, while pointing out that the functional limitations applied to 8 million people in the United States – people whose needs are not being met.

There’s no sign of the trend stopping, he continued. “We saw no downward trend, only an upward trend.”

Increasingly, including functionality as an endpoint in cancer trials, in addition to improvements in mortality, is one place to start, he added.

“Our findings suggest an urgent need for care teams to understand and address function, for researchers to evaluate function as a core outcome in trials, and for health systems and policy makers to reimagine survivorship care, recognizing the burden of cancer and its treatment on physical, psychosocial, and cognitive function,” the authors wrote in their paper. Limitations of the study include the potential for recall bias, lack of cancer staging or treatment information, and the subjective perception of function.

A coauthor reported personal fees from Astellas, AstraZeneca, AAA, Blue Earth, Janssen, Lantheus, Myovant, Myriad Genetics, Novartis, Telix, and Sanofi, as well as grants from Pfizer and Bayer during the conduct of the study. No other disclosures were reported.

Atrial fibrillation (AFib) is a known and serious side effect of some cancer treatments, but it is underreported in cancer drug trials, French investigators said in a new report.

As a result, oncologists likely underestimate the risk of atrial fibrillation when new cancer drugs come to market, they said.

The team came to these conclusions after conducting a meta-analysis of 191 phase 2 or 3 clinical trials that included 26,604 patients. The trials investigated 15 anticancer drugs used as monotherapy.

The meta-analysis showed that the annualized incidence rate of AFib ranged from 0.26 cases per 100 person-years – about the same as placebo – to 4.92 cases, a nearly 20 times’ higher risk.

Rates were the highest for ibrutinib, clofarabine, and ponatinib.

The study was published in JACC: CardioOncology, a journal of the American College of Cardiology.

Actual rates of AFib are probably higher than what they found in this meta-analysis, the authors suspect, because most oncology trials only identify and report severe cases of AFib that require immediate medical attention. Less severe cases can also lead to serious complications, including strokes, but they go unreported, said the investigators, led by Joachim Alexandre, MD, PhD, a member of the cardio-oncology program at the University of Caen Normandie Hospital Center, France.

“These findings suggest a global and systemic underreporting and/or underidentification of cardiotoxicity among cancer clinical trial participants,” and AFib reporting is “particularly affected,” they said.
 

Call for routine monitoring

The root of the problem is the lack of routine rhythm monitoring in cancer trials. This in turn “leads to a significant underestimation of AFib incidence” and rates “markedly lower than those observed among real-life” patients, the authors pointed out.

To address the issue, Dr. Alexandre and his team called for routine cardiac monitoring in trials to capture the true incidence of AFib and to “clearly define which anticancer drugs are significantly associated” with the condition.

Approached for comment, Michael G. Fradley, MD, medical director of cardio-oncology at the University of Pennsylvania, Philadelphia, agreed.

“It’s incredibly important” to “identify the drugs most likely to cause arrhythmias and determine the best prevention and treatment strategies. Unfortunately, systematic evaluation of arrhythmias in cancer clinical trials has often been lacking,” Dr. Fradley told this news organization.

The investigators said the issue is particularly pressing for drugs known to be associated with AFib. For Bruton’s tyrosine kinase inhibitors such as ibrutinib, for instance, they call for standardize AFib detection in trials “not only on 12-lead ECGs” for symptomatic AFib but also with “longer-term ambulatory monitoring or insertable cardiac monitors to detect subclinical AFib.”

Dr. Fradley said there might also be a role for newer wearable technologies that can detect arrhythmias through a skin patch or by other means.
 

Details of the meta-analysis

The investigators pulled the 191 studies they used in their meta-analysis from the ClinicalTrials.gov database.

The trials covered anticancer drugs used as monotherapy up to Sept. 18, 2020. Almost half were randomized trials, but only seven had placebo arms. Trials involving hematologic cancers outnumbered those involving solid tumors.

The 15 drugs examined were dacarbazine, abiraterone, clofarabine, azacitidine, ibrutinib, nilotinib, ponatinib, midostaurin, ipilimumab, aldesleukin, lenalidomide, pomalidomide, rituximab, bortezomib, and docetaxel.

The annualized incidence AFib rates per 100 person-years were 4.92 cases for ibrutinib, 2.38 cases for clofarabine, and 2.35 cases for ponatinib.

The lowest AFib rates were for ipilimumab (0.26 cases), rituximab (0.27), and nilotinib (0.29).

For placebo, the annualized rate was 0.25 cases per 100 person-years.

The team said caution is warranted regarding their estimations for clofarabine and midostaurin (0.65 cases) because no trials were registered after September 2009, when adverse event reporting became mandatory. As a result, estimates may be artificially low.

One of the limits of the study is that it focused on monotherapy in an age when combination treatment is generally the rule for cancer, the authors noted.

No external funding was reported for the study. Dr. Alexandre has received honoraria for presentations and consulting fees from Bayer, BMS, Pfizer, Amgen, and Bioserenity.
 

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

Atrial fibrillation (AFib) is a known and serious side effect of some cancer treatments, but it is underreported in cancer drug trials, French investigators said in a new report.

As a result, oncologists likely underestimate the risk of atrial fibrillation when new cancer drugs come to market, they said.

The team came to these conclusions after conducting a meta-analysis of 191 phase 2 or 3 clinical trials that included 26,604 patients. The trials investigated 15 anticancer drugs used as monotherapy.

The meta-analysis showed that the annualized incidence rate of AFib ranged from 0.26 cases per 100 person-years – about the same as placebo – to 4.92 cases, a nearly 20 times’ higher risk.

Rates were the highest for ibrutinib, clofarabine, and ponatinib.

The study was published in JACC: CardioOncology, a journal of the American College of Cardiology.

Actual rates of AFib are probably higher than what they found in this meta-analysis, the authors suspect, because most oncology trials only identify and report severe cases of AFib that require immediate medical attention. Less severe cases can also lead to serious complications, including strokes, but they go unreported, said the investigators, led by Joachim Alexandre, MD, PhD, a member of the cardio-oncology program at the University of Caen Normandie Hospital Center, France.

“These findings suggest a global and systemic underreporting and/or underidentification of cardiotoxicity among cancer clinical trial participants,” and AFib reporting is “particularly affected,” they said.
 

Call for routine monitoring

The root of the problem is the lack of routine rhythm monitoring in cancer trials. This in turn “leads to a significant underestimation of AFib incidence” and rates “markedly lower than those observed among real-life” patients, the authors pointed out.

To address the issue, Dr. Alexandre and his team called for routine cardiac monitoring in trials to capture the true incidence of AFib and to “clearly define which anticancer drugs are significantly associated” with the condition.

Approached for comment, Michael G. Fradley, MD, medical director of cardio-oncology at the University of Pennsylvania, Philadelphia, agreed.

“It’s incredibly important” to “identify the drugs most likely to cause arrhythmias and determine the best prevention and treatment strategies. Unfortunately, systematic evaluation of arrhythmias in cancer clinical trials has often been lacking,” Dr. Fradley told this news organization.

The investigators said the issue is particularly pressing for drugs known to be associated with AFib. For Bruton’s tyrosine kinase inhibitors such as ibrutinib, for instance, they call for standardize AFib detection in trials “not only on 12-lead ECGs” for symptomatic AFib but also with “longer-term ambulatory monitoring or insertable cardiac monitors to detect subclinical AFib.”

Dr. Fradley said there might also be a role for newer wearable technologies that can detect arrhythmias through a skin patch or by other means.
 

Details of the meta-analysis

The investigators pulled the 191 studies they used in their meta-analysis from the ClinicalTrials.gov database.

The trials covered anticancer drugs used as monotherapy up to Sept. 18, 2020. Almost half were randomized trials, but only seven had placebo arms. Trials involving hematologic cancers outnumbered those involving solid tumors.

The 15 drugs examined were dacarbazine, abiraterone, clofarabine, azacitidine, ibrutinib, nilotinib, ponatinib, midostaurin, ipilimumab, aldesleukin, lenalidomide, pomalidomide, rituximab, bortezomib, and docetaxel.

The annualized incidence AFib rates per 100 person-years were 4.92 cases for ibrutinib, 2.38 cases for clofarabine, and 2.35 cases for ponatinib.

The lowest AFib rates were for ipilimumab (0.26 cases), rituximab (0.27), and nilotinib (0.29).

For placebo, the annualized rate was 0.25 cases per 100 person-years.

The team said caution is warranted regarding their estimations for clofarabine and midostaurin (0.65 cases) because no trials were registered after September 2009, when adverse event reporting became mandatory. As a result, estimates may be artificially low.

One of the limits of the study is that it focused on monotherapy in an age when combination treatment is generally the rule for cancer, the authors noted.

No external funding was reported for the study. Dr. Alexandre has received honoraria for presentations and consulting fees from Bayer, BMS, Pfizer, Amgen, and Bioserenity.
 

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

Atrial fibrillation (AFib) is a known and serious side effect of some cancer treatments, but it is underreported in cancer drug trials, French investigators said in a new report.

As a result, oncologists likely underestimate the risk of atrial fibrillation when new cancer drugs come to market, they said.

The team came to these conclusions after conducting a meta-analysis of 191 phase 2 or 3 clinical trials that included 26,604 patients. The trials investigated 15 anticancer drugs used as monotherapy.

The meta-analysis showed that the annualized incidence rate of AFib ranged from 0.26 cases per 100 person-years – about the same as placebo – to 4.92 cases, a nearly 20 times’ higher risk.

Rates were the highest for ibrutinib, clofarabine, and ponatinib.

The study was published in JACC: CardioOncology, a journal of the American College of Cardiology.

Actual rates of AFib are probably higher than what they found in this meta-analysis, the authors suspect, because most oncology trials only identify and report severe cases of AFib that require immediate medical attention. Less severe cases can also lead to serious complications, including strokes, but they go unreported, said the investigators, led by Joachim Alexandre, MD, PhD, a member of the cardio-oncology program at the University of Caen Normandie Hospital Center, France.

“These findings suggest a global and systemic underreporting and/or underidentification of cardiotoxicity among cancer clinical trial participants,” and AFib reporting is “particularly affected,” they said.
 

Call for routine monitoring

The root of the problem is the lack of routine rhythm monitoring in cancer trials. This in turn “leads to a significant underestimation of AFib incidence” and rates “markedly lower than those observed among real-life” patients, the authors pointed out.

To address the issue, Dr. Alexandre and his team called for routine cardiac monitoring in trials to capture the true incidence of AFib and to “clearly define which anticancer drugs are significantly associated” with the condition.

Approached for comment, Michael G. Fradley, MD, medical director of cardio-oncology at the University of Pennsylvania, Philadelphia, agreed.

“It’s incredibly important” to “identify the drugs most likely to cause arrhythmias and determine the best prevention and treatment strategies. Unfortunately, systematic evaluation of arrhythmias in cancer clinical trials has often been lacking,” Dr. Fradley told this news organization.

The investigators said the issue is particularly pressing for drugs known to be associated with AFib. For Bruton’s tyrosine kinase inhibitors such as ibrutinib, for instance, they call for standardize AFib detection in trials “not only on 12-lead ECGs” for symptomatic AFib but also with “longer-term ambulatory monitoring or insertable cardiac monitors to detect subclinical AFib.”

Dr. Fradley said there might also be a role for newer wearable technologies that can detect arrhythmias through a skin patch or by other means.
 

Details of the meta-analysis

The investigators pulled the 191 studies they used in their meta-analysis from the ClinicalTrials.gov database.

The trials covered anticancer drugs used as monotherapy up to Sept. 18, 2020. Almost half were randomized trials, but only seven had placebo arms. Trials involving hematologic cancers outnumbered those involving solid tumors.

The 15 drugs examined were dacarbazine, abiraterone, clofarabine, azacitidine, ibrutinib, nilotinib, ponatinib, midostaurin, ipilimumab, aldesleukin, lenalidomide, pomalidomide, rituximab, bortezomib, and docetaxel.

The annualized incidence AFib rates per 100 person-years were 4.92 cases for ibrutinib, 2.38 cases for clofarabine, and 2.35 cases for ponatinib.

The lowest AFib rates were for ipilimumab (0.26 cases), rituximab (0.27), and nilotinib (0.29).

For placebo, the annualized rate was 0.25 cases per 100 person-years.

The team said caution is warranted regarding their estimations for clofarabine and midostaurin (0.65 cases) because no trials were registered after September 2009, when adverse event reporting became mandatory. As a result, estimates may be artificially low.

One of the limits of the study is that it focused on monotherapy in an age when combination treatment is generally the rule for cancer, the authors noted.

No external funding was reported for the study. Dr. Alexandre has received honoraria for presentations and consulting fees from Bayer, BMS, Pfizer, Amgen, and Bioserenity.
 

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

NEW ORLEANS – Atorvastatin treatment of patients with lymphoma undergoing treatment with an anthracycline significantly cut the incidence of incident cardiac dysfunction by about two-thirds during 12 months of treatment, in a multicenter, randomized trial with 300 enrolled patients.

“These data support the use of atorvastatin among patients with lymphoma being treated with anthracyclines where prevention of cardiac systolic dysfunction is important,” concluded Tomas G. Neilan, MD, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Mitchel L. Zoler/MDedge News

He highlighted that an important difference between the new study, STOP-CA, and a major prior study with a neutral effect published in 2022, was that STOP-CA “was powered for a major change” in cardiac function as the study’s primary outcome, a decline from baseline in left ventricular ejection fraction (LVEF) of at least 10% that also reduced ejection fraction to less than 55%.

“We can consider these medications [atorvastatin] for patients at higher risk for cardiac toxicity from anthracyclines, such as patients who receive a higher dose of an anthracycline, older patients, people with obesity, and women, commented Anita Deswal, MD, professor and chair of the department of cardiology at the University of Texas MD Anderson Cancer Center, Houston, who was not involved with the study.
 

A basis for an ‘important discussion’ with patients

“For patients receiving higher doses of anthracyclines, the STOP-CA trial says that whether to start a statin for cardiac protection is now an important discussion” for these patients to have with their treating clinicians. ”That was not the case before today,” commented Ronald M. Witteles, MD, a cardiologist and professor who specializes in cardio-oncology at Stanford (Calif.) University.

“For a patient being treated for lymphoma or for another cancer and treated with equal or higher anthracycline doses, such as patients with a sarcoma, this trial’s results at the very least warrant a discussion between physicians and patients to make the decision,” Dr. Witteles, who was not involved in the study, said in an interview. But he also cautioned that “whether an individual patient should take a statin in this scenario is still not a no-brainer. While the trial was positive, it was for an imaging rather than for a clinical endpoint.”

Experts noted that a similar study with the clinical endpoint of heart failure would require both many more randomized patients as well as much longer follow-up. STOP-CA was not powered for this endpoint. During its 12-month duration, a total of 11 patients developed heart failure, with no between group difference.

STOP-CA enrolled adults with lymphoma (Hodgkin or non-Hodgkin) and scheduled to undergo anthracycline treatment at eight U.S. centers and one in Canada, and excluded patients already on statin treatment or those for whom a statin was already indicated. Of the 300 enrolled patients, 286 had 12-month follow-up. Randomization assigned patients to receive either 40 mg daily of atorvastatin or placebo.

Their cumulative, median anthracycline dose was 300 mg/m², which is typical for treating lymphoma, but higher than the typical dose use for patients with breast cancer. At baseline, average LVEF was 63%, and after 12 months this had declined to 59%. Forty-six of the 286 patients assessed after 12 months fulfilled the primary outcome of at least a 10–percentage point reduction from baseline in their LVEF and a decline in LVEF to less than 55%. Researchers used cardiac MR to assess LVEF at baseline, and in most patients at follow-up, but a minority of patients had their follow-up assessments by echocardiography because of logistical issues. Greater than 90% of patients were adherent to their assigned regimen.

Tripled incidence of cardiac dysfunction in placebo patients

The incidence of this outcome was 9% among the patients who received atorvastatin, and 22% among those on placebo, a significant difference. The calculated odds of the primary outcome was 2.9-fold more likely among the patients treated with placebo, compared with those who received atorvastatin, also a significant difference.

The study’s secondary outcome was patients who had at least a 5% drop from baseline in their LVEF and with a LVEF of less than 55% after 12 months. This outcome occurred in 13% of patients treated with atorvastatin and in 29% of those who received placebo, a significant difference.

The atorvastatin and placebo arms showed no significant differences in adverse events during the study, with roughly similar incidence rates for muscle pain, elevated liver enzymes, and renal failure. None of the enrolled patients developed myositis.

Atorvastatin treatment also produced an expected average 37% decline from baseline in levels of LDL cholesterol.

“This was a well-designed and important trial,” said Dr. Witteles. “Anthracyclines remain a mainstay of cancer therapies for a number of malignancies, such as lymphoma and sarcoma, and the cardiac side effects of development of cardiac dysfunction are unequivocally real.”
 

The importance of a clinically meaningful effect

The results especially contrast with the findings from the PREVENT study, published in 2022, which compared a daily, 40-mg atorvastatin treatment with placebo in 279 randomized patients with breast cancer and treated for 24 months. However, patients in PREVENT had a cumulative, median anthracycline dose of 240 mg/m², and the study’s primary outcome was the average change from baseline in LVEF after 24 months of treatment, which was a reduction of 0.08 percentage points in the placebo arm, a nonsignificant difference.

In STOP-CA, the average change in LVEF from baseline was a 1–percentage point reduction in the placebo arm, compared with the atorvastatin-treated patients, a difference that was statistically significant, but “not clinically significant,” said Dr. Neilan, director of the cardio-oncology program at Massachusetts General Hospital, Boston. He cited the good fortune of the STOP-CA investigators when they received a recommendation from reviewers early on to design their study to track a clinically meaningful change in LVEF rather than just looking at the average overall change.

Mitchel L. Zoler/MDedge News

Dr. Deswal also noted that it is unlikely that future studies will examine the efficacy of a statin for preventing LVEF in patients across the range of cancers that are eligible for anthracycline treatment. As a result, she predicted that “we may have to extrapolate” the results from STOP-CA to patients with other cancer types.

STOP-CA received no commercial funding. Dr. Neilan has been a consultant for and received fees from Abbvie, Amgen, Bristol-Myers Squibb, CRC Oncology, Genentech, Roche, and Sanofi, and has received grant funding from AstraZeneca and Bristol Myers Squib. Dr. Deswal and Dr. Witteles had no relevant disclosures.

NEW ORLEANS – Atorvastatin treatment of patients with lymphoma undergoing treatment with an anthracycline significantly cut the incidence of incident cardiac dysfunction by about two-thirds during 12 months of treatment, in a multicenter, randomized trial with 300 enrolled patients.

“These data support the use of atorvastatin among patients with lymphoma being treated with anthracyclines where prevention of cardiac systolic dysfunction is important,” concluded Tomas G. Neilan, MD, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Mitchel L. Zoler/MDedge News

He highlighted that an important difference between the new study, STOP-CA, and a major prior study with a neutral effect published in 2022, was that STOP-CA “was powered for a major change” in cardiac function as the study’s primary outcome, a decline from baseline in left ventricular ejection fraction (LVEF) of at least 10% that also reduced ejection fraction to less than 55%.

“We can consider these medications [atorvastatin] for patients at higher risk for cardiac toxicity from anthracyclines, such as patients who receive a higher dose of an anthracycline, older patients, people with obesity, and women, commented Anita Deswal, MD, professor and chair of the department of cardiology at the University of Texas MD Anderson Cancer Center, Houston, who was not involved with the study.
 

A basis for an ‘important discussion’ with patients

“For patients receiving higher doses of anthracyclines, the STOP-CA trial says that whether to start a statin for cardiac protection is now an important discussion” for these patients to have with their treating clinicians. ”That was not the case before today,” commented Ronald M. Witteles, MD, a cardiologist and professor who specializes in cardio-oncology at Stanford (Calif.) University.

“For a patient being treated for lymphoma or for another cancer and treated with equal or higher anthracycline doses, such as patients with a sarcoma, this trial’s results at the very least warrant a discussion between physicians and patients to make the decision,” Dr. Witteles, who was not involved in the study, said in an interview. But he also cautioned that “whether an individual patient should take a statin in this scenario is still not a no-brainer. While the trial was positive, it was for an imaging rather than for a clinical endpoint.”

Experts noted that a similar study with the clinical endpoint of heart failure would require both many more randomized patients as well as much longer follow-up. STOP-CA was not powered for this endpoint. During its 12-month duration, a total of 11 patients developed heart failure, with no between group difference.

STOP-CA enrolled adults with lymphoma (Hodgkin or non-Hodgkin) and scheduled to undergo anthracycline treatment at eight U.S. centers and one in Canada, and excluded patients already on statin treatment or those for whom a statin was already indicated. Of the 300 enrolled patients, 286 had 12-month follow-up. Randomization assigned patients to receive either 40 mg daily of atorvastatin or placebo.

Their cumulative, median anthracycline dose was 300 mg/m², which is typical for treating lymphoma, but higher than the typical dose use for patients with breast cancer. At baseline, average LVEF was 63%, and after 12 months this had declined to 59%. Forty-six of the 286 patients assessed after 12 months fulfilled the primary outcome of at least a 10–percentage point reduction from baseline in their LVEF and a decline in LVEF to less than 55%. Researchers used cardiac MR to assess LVEF at baseline, and in most patients at follow-up, but a minority of patients had their follow-up assessments by echocardiography because of logistical issues. Greater than 90% of patients were adherent to their assigned regimen.

Tripled incidence of cardiac dysfunction in placebo patients

The incidence of this outcome was 9% among the patients who received atorvastatin, and 22% among those on placebo, a significant difference. The calculated odds of the primary outcome was 2.9-fold more likely among the patients treated with placebo, compared with those who received atorvastatin, also a significant difference.

The study’s secondary outcome was patients who had at least a 5% drop from baseline in their LVEF and with a LVEF of less than 55% after 12 months. This outcome occurred in 13% of patients treated with atorvastatin and in 29% of those who received placebo, a significant difference.

The atorvastatin and placebo arms showed no significant differences in adverse events during the study, with roughly similar incidence rates for muscle pain, elevated liver enzymes, and renal failure. None of the enrolled patients developed myositis.

Atorvastatin treatment also produced an expected average 37% decline from baseline in levels of LDL cholesterol.

“This was a well-designed and important trial,” said Dr. Witteles. “Anthracyclines remain a mainstay of cancer therapies for a number of malignancies, such as lymphoma and sarcoma, and the cardiac side effects of development of cardiac dysfunction are unequivocally real.”
 

The importance of a clinically meaningful effect

The results especially contrast with the findings from the PREVENT study, published in 2022, which compared a daily, 40-mg atorvastatin treatment with placebo in 279 randomized patients with breast cancer and treated for 24 months. However, patients in PREVENT had a cumulative, median anthracycline dose of 240 mg/m², and the study’s primary outcome was the average change from baseline in LVEF after 24 months of treatment, which was a reduction of 0.08 percentage points in the placebo arm, a nonsignificant difference.

In STOP-CA, the average change in LVEF from baseline was a 1–percentage point reduction in the placebo arm, compared with the atorvastatin-treated patients, a difference that was statistically significant, but “not clinically significant,” said Dr. Neilan, director of the cardio-oncology program at Massachusetts General Hospital, Boston. He cited the good fortune of the STOP-CA investigators when they received a recommendation from reviewers early on to design their study to track a clinically meaningful change in LVEF rather than just looking at the average overall change.

Mitchel L. Zoler/MDedge News

Dr. Deswal also noted that it is unlikely that future studies will examine the efficacy of a statin for preventing LVEF in patients across the range of cancers that are eligible for anthracycline treatment. As a result, she predicted that “we may have to extrapolate” the results from STOP-CA to patients with other cancer types.

STOP-CA received no commercial funding. Dr. Neilan has been a consultant for and received fees from Abbvie, Amgen, Bristol-Myers Squibb, CRC Oncology, Genentech, Roche, and Sanofi, and has received grant funding from AstraZeneca and Bristol Myers Squib. Dr. Deswal and Dr. Witteles had no relevant disclosures.

NEW ORLEANS – Atorvastatin treatment of patients with lymphoma undergoing treatment with an anthracycline significantly cut the incidence of incident cardiac dysfunction by about two-thirds during 12 months of treatment, in a multicenter, randomized trial with 300 enrolled patients.

“These data support the use of atorvastatin among patients with lymphoma being treated with anthracyclines where prevention of cardiac systolic dysfunction is important,” concluded Tomas G. Neilan, MD, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Mitchel L. Zoler/MDedge News

He highlighted that an important difference between the new study, STOP-CA, and a major prior study with a neutral effect published in 2022, was that STOP-CA “was powered for a major change” in cardiac function as the study’s primary outcome, a decline from baseline in left ventricular ejection fraction (LVEF) of at least 10% that also reduced ejection fraction to less than 55%.

“We can consider these medications [atorvastatin] for patients at higher risk for cardiac toxicity from anthracyclines, such as patients who receive a higher dose of an anthracycline, older patients, people with obesity, and women, commented Anita Deswal, MD, professor and chair of the department of cardiology at the University of Texas MD Anderson Cancer Center, Houston, who was not involved with the study.
 

A basis for an ‘important discussion’ with patients

“For patients receiving higher doses of anthracyclines, the STOP-CA trial says that whether to start a statin for cardiac protection is now an important discussion” for these patients to have with their treating clinicians. ”That was not the case before today,” commented Ronald M. Witteles, MD, a cardiologist and professor who specializes in cardio-oncology at Stanford (Calif.) University.

“For a patient being treated for lymphoma or for another cancer and treated with equal or higher anthracycline doses, such as patients with a sarcoma, this trial’s results at the very least warrant a discussion between physicians and patients to make the decision,” Dr. Witteles, who was not involved in the study, said in an interview. But he also cautioned that “whether an individual patient should take a statin in this scenario is still not a no-brainer. While the trial was positive, it was for an imaging rather than for a clinical endpoint.”

Experts noted that a similar study with the clinical endpoint of heart failure would require both many more randomized patients as well as much longer follow-up. STOP-CA was not powered for this endpoint. During its 12-month duration, a total of 11 patients developed heart failure, with no between group difference.

STOP-CA enrolled adults with lymphoma (Hodgkin or non-Hodgkin) and scheduled to undergo anthracycline treatment at eight U.S. centers and one in Canada, and excluded patients already on statin treatment or those for whom a statin was already indicated. Of the 300 enrolled patients, 286 had 12-month follow-up. Randomization assigned patients to receive either 40 mg daily of atorvastatin or placebo.

Their cumulative, median anthracycline dose was 300 mg/m², which is typical for treating lymphoma, but higher than the typical dose use for patients with breast cancer. At baseline, average LVEF was 63%, and after 12 months this had declined to 59%. Forty-six of the 286 patients assessed after 12 months fulfilled the primary outcome of at least a 10–percentage point reduction from baseline in their LVEF and a decline in LVEF to less than 55%. Researchers used cardiac MR to assess LVEF at baseline, and in most patients at follow-up, but a minority of patients had their follow-up assessments by echocardiography because of logistical issues. Greater than 90% of patients were adherent to their assigned regimen.

Tripled incidence of cardiac dysfunction in placebo patients

The incidence of this outcome was 9% among the patients who received atorvastatin, and 22% among those on placebo, a significant difference. The calculated odds of the primary outcome was 2.9-fold more likely among the patients treated with placebo, compared with those who received atorvastatin, also a significant difference.

The study’s secondary outcome was patients who had at least a 5% drop from baseline in their LVEF and with a LVEF of less than 55% after 12 months. This outcome occurred in 13% of patients treated with atorvastatin and in 29% of those who received placebo, a significant difference.

The atorvastatin and placebo arms showed no significant differences in adverse events during the study, with roughly similar incidence rates for muscle pain, elevated liver enzymes, and renal failure. None of the enrolled patients developed myositis.

Atorvastatin treatment also produced an expected average 37% decline from baseline in levels of LDL cholesterol.

“This was a well-designed and important trial,” said Dr. Witteles. “Anthracyclines remain a mainstay of cancer therapies for a number of malignancies, such as lymphoma and sarcoma, and the cardiac side effects of development of cardiac dysfunction are unequivocally real.”
 

The importance of a clinically meaningful effect

The results especially contrast with the findings from the PREVENT study, published in 2022, which compared a daily, 40-mg atorvastatin treatment with placebo in 279 randomized patients with breast cancer and treated for 24 months. However, patients in PREVENT had a cumulative, median anthracycline dose of 240 mg/m², and the study’s primary outcome was the average change from baseline in LVEF after 24 months of treatment, which was a reduction of 0.08 percentage points in the placebo arm, a nonsignificant difference.

In STOP-CA, the average change in LVEF from baseline was a 1–percentage point reduction in the placebo arm, compared with the atorvastatin-treated patients, a difference that was statistically significant, but “not clinically significant,” said Dr. Neilan, director of the cardio-oncology program at Massachusetts General Hospital, Boston. He cited the good fortune of the STOP-CA investigators when they received a recommendation from reviewers early on to design their study to track a clinically meaningful change in LVEF rather than just looking at the average overall change.

Mitchel L. Zoler/MDedge News

Dr. Deswal also noted that it is unlikely that future studies will examine the efficacy of a statin for preventing LVEF in patients across the range of cancers that are eligible for anthracycline treatment. As a result, she predicted that “we may have to extrapolate” the results from STOP-CA to patients with other cancer types.

STOP-CA received no commercial funding. Dr. Neilan has been a consultant for and received fees from Abbvie, Amgen, Bristol-Myers Squibb, CRC Oncology, Genentech, Roche, and Sanofi, and has received grant funding from AstraZeneca and Bristol Myers Squib. Dr. Deswal and Dr. Witteles had no relevant disclosures.

Patients with hematologic disease who develop COVID-19 may experience substantial morbidity and mortality related to SARS-CoV-2 infection, according to recent registry data reported at the all-virtual annual meeting of the American Society of Hematology.

Overall mortality was 28% for the first 250 patients entered into the ASH Research Collaborative COVID-19 Registry for Hematology, researchers reported in an abstract of their study findings.

However, the burden of death and moderate-to-severe COVID-19 outcomes was highest in patients with poorer prognosis and those with relapsed/refractory hematological disease, they added.

The most commonly represented malignancies were acute leukemia, non-Hodgkin lymphoma, and myeloma or amyloidosis, according to the report.

Taken together, the findings do support an “emerging consensus” that COVID-19 related morbidity and mortality is significant in these patients, authors said – however, the current findings may not be reason enough to support a change in treatment course for the underlying disease.

“We see no reason, based on our data, to withhold intensive therapies from patients with underlying hematologic malignancies and favorable prognoses, if aggressive supportive care is consistent with patient preferences,” wrote the researchers.

ASH President Stephanie Lee, MD, MPH, said these registry findings are important to better understand how SARS-CoV-2 is affecting not only patients with hematologic diseases, but also individuals who experience COVID-19-related hematologic complications.

However, the findings are limited due to the heterogeneity of diseases, symptoms, and treatments represented in the registry, said Dr. Lee, associate director of the clinical research division at Fred Hutchinson Cancer Center in Seattle.

“More data will be coming in, but I think this is an example of trying to harness real-world information to try to learn things until we get more controlled studies,” Dr. Lee said in a media briefing held in advance of the ASH meeting.
 

Comorbidities and more

Patients with blood cancers are often older and may have comorbidities such as diabetes or hypertension that have been linked to poor COVID-19 outcomes, according to the authors of the report, led by William A. Wood, MD, MPH, associate professor of medicine with the UNC Lineberger Comprehensive Cancer Center in Chapel Hill, N.C.

Moreover, these patients may have underlying immune dysfunction and may receive chemotherapy or immunotherapy that is “profoundly immunosuppressive,” Dr. Wood and coauthors said in their report.

To date, however, risks of morbidity and mortality related to SARS-CoV-2 infection have not been well defined in this patient population, authors said.

More data is emerging now from the ASH Research Collaborative COVID-19 Registry for Hematology, which includes data on patients positive for COVID-19 who have a past or present hematologic condition or have experienced a hematologic complication related to COVID-19.

All data from the registry is being made available through a dashboard on the ASH Research Collaborative website, which as of Dec. 1, 2020, included 693 complete cases.

The data cut in the ASH abstract includes the first 250 patients enrolled at 74 sites around the world, the authors said. The most common malignancies included acute leukemia in 33%, non-Hodgkin lymphoma in 27%, and myeloma or amyloidosis in 16%.

The most frequently reported symptoms included fever in 73%, cough in 67%, dyspnea in 50%, and fatigue in 40%, according to that report.

At the time of this data snapshot, treatment with COVID-19-directed therapies including hydroxychloroquine or azithromycin were common, reported in 76 and 59 patients, respectively, in the cohort.

Batch submissions from sites with high incidence of COVID-19 infection are ongoing. The registry has been expanded to include nonmalignant hematologic diseases, and the registry will continue to accumulate data as a resource for the hematology community.

Overall mortality was 28% at the time, according to the abstract, with nearly all of the deaths occurring in patients classified as having COVID-19 that was moderate (i.e., requiring hospitalization) or severe (i.e., requiring ICU admission).

“In some instances, death occurred after a decision was made to forgo ICU admission in favor of a palliative approach,” said Dr. Wood and coauthors in their report.

Dr. Wood reported research funding from Pfizer, consultancy with Teladoc/Best Doctors, and honoraria from the ASH Research Collaborative. Coauthors provided disclosures related to Celgene, Madrigal Pharmaceuticals, Pharmacyclics, and Amgen, among others.

SOURCE: Wood WA et al. ASH 2020, Abstract 215.

Patients with hematologic disease who develop COVID-19 may experience substantial morbidity and mortality related to SARS-CoV-2 infection, according to recent registry data reported at the all-virtual annual meeting of the American Society of Hematology.

Overall mortality was 28% for the first 250 patients entered into the ASH Research Collaborative COVID-19 Registry for Hematology, researchers reported in an abstract of their study findings.

However, the burden of death and moderate-to-severe COVID-19 outcomes was highest in patients with poorer prognosis and those with relapsed/refractory hematological disease, they added.

The most commonly represented malignancies were acute leukemia, non-Hodgkin lymphoma, and myeloma or amyloidosis, according to the report.

Taken together, the findings do support an “emerging consensus” that COVID-19 related morbidity and mortality is significant in these patients, authors said – however, the current findings may not be reason enough to support a change in treatment course for the underlying disease.

“We see no reason, based on our data, to withhold intensive therapies from patients with underlying hematologic malignancies and favorable prognoses, if aggressive supportive care is consistent with patient preferences,” wrote the researchers.

ASH President Stephanie Lee, MD, MPH, said these registry findings are important to better understand how SARS-CoV-2 is affecting not only patients with hematologic diseases, but also individuals who experience COVID-19-related hematologic complications.

However, the findings are limited due to the heterogeneity of diseases, symptoms, and treatments represented in the registry, said Dr. Lee, associate director of the clinical research division at Fred Hutchinson Cancer Center in Seattle.

“More data will be coming in, but I think this is an example of trying to harness real-world information to try to learn things until we get more controlled studies,” Dr. Lee said in a media briefing held in advance of the ASH meeting.
 

Comorbidities and more

Patients with blood cancers are often older and may have comorbidities such as diabetes or hypertension that have been linked to poor COVID-19 outcomes, according to the authors of the report, led by William A. Wood, MD, MPH, associate professor of medicine with the UNC Lineberger Comprehensive Cancer Center in Chapel Hill, N.C.

Moreover, these patients may have underlying immune dysfunction and may receive chemotherapy or immunotherapy that is “profoundly immunosuppressive,” Dr. Wood and coauthors said in their report.

To date, however, risks of morbidity and mortality related to SARS-CoV-2 infection have not been well defined in this patient population, authors said.

More data is emerging now from the ASH Research Collaborative COVID-19 Registry for Hematology, which includes data on patients positive for COVID-19 who have a past or present hematologic condition or have experienced a hematologic complication related to COVID-19.

All data from the registry is being made available through a dashboard on the ASH Research Collaborative website, which as of Dec. 1, 2020, included 693 complete cases.

The data cut in the ASH abstract includes the first 250 patients enrolled at 74 sites around the world, the authors said. The most common malignancies included acute leukemia in 33%, non-Hodgkin lymphoma in 27%, and myeloma or amyloidosis in 16%.

The most frequently reported symptoms included fever in 73%, cough in 67%, dyspnea in 50%, and fatigue in 40%, according to that report.

At the time of this data snapshot, treatment with COVID-19-directed therapies including hydroxychloroquine or azithromycin were common, reported in 76 and 59 patients, respectively, in the cohort.

Batch submissions from sites with high incidence of COVID-19 infection are ongoing. The registry has been expanded to include nonmalignant hematologic diseases, and the registry will continue to accumulate data as a resource for the hematology community.

Overall mortality was 28% at the time, according to the abstract, with nearly all of the deaths occurring in patients classified as having COVID-19 that was moderate (i.e., requiring hospitalization) or severe (i.e., requiring ICU admission).

“In some instances, death occurred after a decision was made to forgo ICU admission in favor of a palliative approach,” said Dr. Wood and coauthors in their report.

Dr. Wood reported research funding from Pfizer, consultancy with Teladoc/Best Doctors, and honoraria from the ASH Research Collaborative. Coauthors provided disclosures related to Celgene, Madrigal Pharmaceuticals, Pharmacyclics, and Amgen, among others.

SOURCE: Wood WA et al. ASH 2020, Abstract 215.

Patients with hematologic disease who develop COVID-19 may experience substantial morbidity and mortality related to SARS-CoV-2 infection, according to recent registry data reported at the all-virtual annual meeting of the American Society of Hematology.

Overall mortality was 28% for the first 250 patients entered into the ASH Research Collaborative COVID-19 Registry for Hematology, researchers reported in an abstract of their study findings.

However, the burden of death and moderate-to-severe COVID-19 outcomes was highest in patients with poorer prognosis and those with relapsed/refractory hematological disease, they added.

The most commonly represented malignancies were acute leukemia, non-Hodgkin lymphoma, and myeloma or amyloidosis, according to the report.

Taken together, the findings do support an “emerging consensus” that COVID-19 related morbidity and mortality is significant in these patients, authors said – however, the current findings may not be reason enough to support a change in treatment course for the underlying disease.

“We see no reason, based on our data, to withhold intensive therapies from patients with underlying hematologic malignancies and favorable prognoses, if aggressive supportive care is consistent with patient preferences,” wrote the researchers.

ASH President Stephanie Lee, MD, MPH, said these registry findings are important to better understand how SARS-CoV-2 is affecting not only patients with hematologic diseases, but also individuals who experience COVID-19-related hematologic complications.

However, the findings are limited due to the heterogeneity of diseases, symptoms, and treatments represented in the registry, said Dr. Lee, associate director of the clinical research division at Fred Hutchinson Cancer Center in Seattle.

“More data will be coming in, but I think this is an example of trying to harness real-world information to try to learn things until we get more controlled studies,” Dr. Lee said in a media briefing held in advance of the ASH meeting.
 

Comorbidities and more

Patients with blood cancers are often older and may have comorbidities such as diabetes or hypertension that have been linked to poor COVID-19 outcomes, according to the authors of the report, led by William A. Wood, MD, MPH, associate professor of medicine with the UNC Lineberger Comprehensive Cancer Center in Chapel Hill, N.C.

Moreover, these patients may have underlying immune dysfunction and may receive chemotherapy or immunotherapy that is “profoundly immunosuppressive,” Dr. Wood and coauthors said in their report.

To date, however, risks of morbidity and mortality related to SARS-CoV-2 infection have not been well defined in this patient population, authors said.

More data is emerging now from the ASH Research Collaborative COVID-19 Registry for Hematology, which includes data on patients positive for COVID-19 who have a past or present hematologic condition or have experienced a hematologic complication related to COVID-19.

All data from the registry is being made available through a dashboard on the ASH Research Collaborative website, which as of Dec. 1, 2020, included 693 complete cases.

The data cut in the ASH abstract includes the first 250 patients enrolled at 74 sites around the world, the authors said. The most common malignancies included acute leukemia in 33%, non-Hodgkin lymphoma in 27%, and myeloma or amyloidosis in 16%.

The most frequently reported symptoms included fever in 73%, cough in 67%, dyspnea in 50%, and fatigue in 40%, according to that report.

At the time of this data snapshot, treatment with COVID-19-directed therapies including hydroxychloroquine or azithromycin were common, reported in 76 and 59 patients, respectively, in the cohort.

Batch submissions from sites with high incidence of COVID-19 infection are ongoing. The registry has been expanded to include nonmalignant hematologic diseases, and the registry will continue to accumulate data as a resource for the hematology community.

Overall mortality was 28% at the time, according to the abstract, with nearly all of the deaths occurring in patients classified as having COVID-19 that was moderate (i.e., requiring hospitalization) or severe (i.e., requiring ICU admission).

“In some instances, death occurred after a decision was made to forgo ICU admission in favor of a palliative approach,” said Dr. Wood and coauthors in their report.

Dr. Wood reported research funding from Pfizer, consultancy with Teladoc/Best Doctors, and honoraria from the ASH Research Collaborative. Coauthors provided disclosures related to Celgene, Madrigal Pharmaceuticals, Pharmacyclics, and Amgen, among others.

SOURCE: Wood WA et al. ASH 2020, Abstract 215.

ORLANDO – Patients with diffuse large B-cell lymphoma (DLBCL) who are members of an ethnic or racial minority do not have worse outcomes than whites when they receive appropriate treatment and institutional support, a study on disparities in cancer care shows.

Neil Osterweil/MDedge News

Although previous studies have shown that minorities with DLBCL have worse outcomes than do whites, results of a study comparing outcomes from 155 patients of white heritage with those of 41 patients from black, Hispanic, or other minority backgrounds found no significant differences in either progression-free survival (PFS) or overall survival in 2 years over follow-up, reported Nilanjan Ghosh, MD, PhD, from the Levine Cancer Institute, Atrium Health, in Charlotte, N.C.

He attributes the results to his center’s robust nurse navigation program, equal access among all patients – regardless of ability to pay – to standard treatments, and to the availability of clinical trial participation and stem cell transplantation.

“I think a key message is that if you are able to offer the same treatment and clinical trials to people irrespective of their race or socioeconomic status and can provide support, you can get equal outcomes as long as the biology is the same in both groups,” he said at a briefing prior to presentation of data in an oral abstract session at the annual meeting of the American Society of Hematology.

Dr. Ghosh pointed to four separate studies that showed that minority populations with DLBCL have worse outcomes than did whites, and noted that both uninsured and Medicaid-insured patients have also been shown to have poorer results, suggesting a role of socioeconomic factors in determining who gets optimum care and who does not.

The investigators compared PFS and OS among white and nonwhite patients with DLBCL treated in their institution, which has a safety-net cancer center. They also looked at the frequencies of clinical trial participation and stem cell transplantation between the groups.

The study included all patients with de novo DLBCL who presented to their center during January 2016–January 2019. They used patient-reported descriptors of race/ethnicity to create one of two cohorts: either self-identified whites (155 patients) or nonwhites (41), a group that included black patients, Hispanic patients, Asian Americans, and Native Americans.

The authors collected data on demographics, disease characteristics (including revised International Prognostic Index and double-hit status), insurance data, treatment, trial enrollment, progression, and death.

They found that nonwhites were significantly younger at diagnosis (median 56 vs. 64 years; P = .007), with an even distribution between the sexes in each group.

Two-thirds of both white and nonwhite patients had government insurance (Medicare or Medicaid). Of the remaining patients, 33% of white had private insurance, compared with 27% of nonwhites. No whites were uninsured, but 3 of the 41 nonwhites (7%) had no insurance.

Of the 155 white patients, 121 (86%) received nurse navigation services, as did 33 of 41 (81%) of nonwhites. The services include lodging assistance for homeless patients, transportation services for patients without cars, and care coordination among primary care physicians, oncologists, and other specialists. The services are part of the center’s standard practice, with excess costs, if any, folded into the budget, Dr. Ghosh said.

Looking at disease characteristics and treatment, the investigators found that risk profiles were similar between the groups. A higher percentage of whites had double-hit lymphoma (11% vs. 7%), but this difference was not statistically significant.

The investigators also found that in their program race was not a barrier to optimum therapy, with 96% of whites and 98% of nonwhites receiving frontline therapy with an anthracycline and rituximab-based regimen, and 4% and 2%, respectively received a non–anthracycline based regimen.

In each group, 39% of patients had disease that either relapsed or was refractory to frontline therapy.

In all, 11% of whites and 12% of nonwhites enrolled in clinical trials, 11% and 19%, respectively, underwent stem cell transplantation.

For patients with relapsed/refractory disease, the 2-year PFS rates were 60% for whites, and 63% for nonwhites, and the 2-year OS rates were 74% and 81%, respectively.

Dr. Ghosh and colleagues concluded that “our safety net cancer center, with extensive nurse navigator support and access to standard treatments, stem cell transplants, and cutting-edge clinical trials may abrogate the inferior outcomes in minority populations that have been previously reported.”

The study was internally funded. Dr. Ghosh reported consulting fees, research funding, speakers bureau activity, and/or honoraria from multiple companies.

SOURCE: Hu B et al. ASH 2019. Abstract 425.

ORLANDO – Patients with diffuse large B-cell lymphoma (DLBCL) who are members of an ethnic or racial minority do not have worse outcomes than whites when they receive appropriate treatment and institutional support, a study on disparities in cancer care shows.

Neil Osterweil/MDedge News

Although previous studies have shown that minorities with DLBCL have worse outcomes than do whites, results of a study comparing outcomes from 155 patients of white heritage with those of 41 patients from black, Hispanic, or other minority backgrounds found no significant differences in either progression-free survival (PFS) or overall survival in 2 years over follow-up, reported Nilanjan Ghosh, MD, PhD, from the Levine Cancer Institute, Atrium Health, in Charlotte, N.C.

He attributes the results to his center’s robust nurse navigation program, equal access among all patients – regardless of ability to pay – to standard treatments, and to the availability of clinical trial participation and stem cell transplantation.

“I think a key message is that if you are able to offer the same treatment and clinical trials to people irrespective of their race or socioeconomic status and can provide support, you can get equal outcomes as long as the biology is the same in both groups,” he said at a briefing prior to presentation of data in an oral abstract session at the annual meeting of the American Society of Hematology.

Dr. Ghosh pointed to four separate studies that showed that minority populations with DLBCL have worse outcomes than did whites, and noted that both uninsured and Medicaid-insured patients have also been shown to have poorer results, suggesting a role of socioeconomic factors in determining who gets optimum care and who does not.

The investigators compared PFS and OS among white and nonwhite patients with DLBCL treated in their institution, which has a safety-net cancer center. They also looked at the frequencies of clinical trial participation and stem cell transplantation between the groups.

The study included all patients with de novo DLBCL who presented to their center during January 2016–January 2019. They used patient-reported descriptors of race/ethnicity to create one of two cohorts: either self-identified whites (155 patients) or nonwhites (41), a group that included black patients, Hispanic patients, Asian Americans, and Native Americans.

The authors collected data on demographics, disease characteristics (including revised International Prognostic Index and double-hit status), insurance data, treatment, trial enrollment, progression, and death.

They found that nonwhites were significantly younger at diagnosis (median 56 vs. 64 years; P = .007), with an even distribution between the sexes in each group.

Two-thirds of both white and nonwhite patients had government insurance (Medicare or Medicaid). Of the remaining patients, 33% of white had private insurance, compared with 27% of nonwhites. No whites were uninsured, but 3 of the 41 nonwhites (7%) had no insurance.

Of the 155 white patients, 121 (86%) received nurse navigation services, as did 33 of 41 (81%) of nonwhites. The services include lodging assistance for homeless patients, transportation services for patients without cars, and care coordination among primary care physicians, oncologists, and other specialists. The services are part of the center’s standard practice, with excess costs, if any, folded into the budget, Dr. Ghosh said.

Looking at disease characteristics and treatment, the investigators found that risk profiles were similar between the groups. A higher percentage of whites had double-hit lymphoma (11% vs. 7%), but this difference was not statistically significant.

The investigators also found that in their program race was not a barrier to optimum therapy, with 96% of whites and 98% of nonwhites receiving frontline therapy with an anthracycline and rituximab-based regimen, and 4% and 2%, respectively received a non–anthracycline based regimen.

In each group, 39% of patients had disease that either relapsed or was refractory to frontline therapy.

In all, 11% of whites and 12% of nonwhites enrolled in clinical trials, 11% and 19%, respectively, underwent stem cell transplantation.

For patients with relapsed/refractory disease, the 2-year PFS rates were 60% for whites, and 63% for nonwhites, and the 2-year OS rates were 74% and 81%, respectively.

Dr. Ghosh and colleagues concluded that “our safety net cancer center, with extensive nurse navigator support and access to standard treatments, stem cell transplants, and cutting-edge clinical trials may abrogate the inferior outcomes in minority populations that have been previously reported.”

The study was internally funded. Dr. Ghosh reported consulting fees, research funding, speakers bureau activity, and/or honoraria from multiple companies.

SOURCE: Hu B et al. ASH 2019. Abstract 425.

ORLANDO – Patients with diffuse large B-cell lymphoma (DLBCL) who are members of an ethnic or racial minority do not have worse outcomes than whites when they receive appropriate treatment and institutional support, a study on disparities in cancer care shows.

Neil Osterweil/MDedge News

Although previous studies have shown that minorities with DLBCL have worse outcomes than do whites, results of a study comparing outcomes from 155 patients of white heritage with those of 41 patients from black, Hispanic, or other minority backgrounds found no significant differences in either progression-free survival (PFS) or overall survival in 2 years over follow-up, reported Nilanjan Ghosh, MD, PhD, from the Levine Cancer Institute, Atrium Health, in Charlotte, N.C.

He attributes the results to his center’s robust nurse navigation program, equal access among all patients – regardless of ability to pay – to standard treatments, and to the availability of clinical trial participation and stem cell transplantation.

“I think a key message is that if you are able to offer the same treatment and clinical trials to people irrespective of their race or socioeconomic status and can provide support, you can get equal outcomes as long as the biology is the same in both groups,” he said at a briefing prior to presentation of data in an oral abstract session at the annual meeting of the American Society of Hematology.

Dr. Ghosh pointed to four separate studies that showed that minority populations with DLBCL have worse outcomes than did whites, and noted that both uninsured and Medicaid-insured patients have also been shown to have poorer results, suggesting a role of socioeconomic factors in determining who gets optimum care and who does not.

The investigators compared PFS and OS among white and nonwhite patients with DLBCL treated in their institution, which has a safety-net cancer center. They also looked at the frequencies of clinical trial participation and stem cell transplantation between the groups.

The study included all patients with de novo DLBCL who presented to their center during January 2016–January 2019. They used patient-reported descriptors of race/ethnicity to create one of two cohorts: either self-identified whites (155 patients) or nonwhites (41), a group that included black patients, Hispanic patients, Asian Americans, and Native Americans.

The authors collected data on demographics, disease characteristics (including revised International Prognostic Index and double-hit status), insurance data, treatment, trial enrollment, progression, and death.

They found that nonwhites were significantly younger at diagnosis (median 56 vs. 64 years; P = .007), with an even distribution between the sexes in each group.

Two-thirds of both white and nonwhite patients had government insurance (Medicare or Medicaid). Of the remaining patients, 33% of white had private insurance, compared with 27% of nonwhites. No whites were uninsured, but 3 of the 41 nonwhites (7%) had no insurance.

Of the 155 white patients, 121 (86%) received nurse navigation services, as did 33 of 41 (81%) of nonwhites. The services include lodging assistance for homeless patients, transportation services for patients without cars, and care coordination among primary care physicians, oncologists, and other specialists. The services are part of the center’s standard practice, with excess costs, if any, folded into the budget, Dr. Ghosh said.

Looking at disease characteristics and treatment, the investigators found that risk profiles were similar between the groups. A higher percentage of whites had double-hit lymphoma (11% vs. 7%), but this difference was not statistically significant.

The investigators also found that in their program race was not a barrier to optimum therapy, with 96% of whites and 98% of nonwhites receiving frontline therapy with an anthracycline and rituximab-based regimen, and 4% and 2%, respectively received a non–anthracycline based regimen.

In each group, 39% of patients had disease that either relapsed or was refractory to frontline therapy.

In all, 11% of whites and 12% of nonwhites enrolled in clinical trials, 11% and 19%, respectively, underwent stem cell transplantation.

For patients with relapsed/refractory disease, the 2-year PFS rates were 60% for whites, and 63% for nonwhites, and the 2-year OS rates were 74% and 81%, respectively.

Dr. Ghosh and colleagues concluded that “our safety net cancer center, with extensive nurse navigator support and access to standard treatments, stem cell transplants, and cutting-edge clinical trials may abrogate the inferior outcomes in minority populations that have been previously reported.”

The study was internally funded. Dr. Ghosh reported consulting fees, research funding, speakers bureau activity, and/or honoraria from multiple companies.

SOURCE: Hu B et al. ASH 2019. Abstract 425.

Early-career researchers who are interested in studying mantle cell lymphoma can now apply for a $50,000 grant from the American Society of Clinical Oncology’s Conquer Cancer foundation.

The young investigator grant is for a 1-year period and the award is used to fund a project focused on clinical or translational research on the clinical biology, natural history, prevention, screening, diagnosis, therapy, or epidemiology of MCL.

The purpose of this annual award, according to ASCO, is to fund physicians during the transition from a fellowship program to a faculty appointment.

Eligible applicants must be physicians currently in the last 2 years of final subspecialty training and within 10 years of having obtained his or her medical degree. Additionally, applicants must be planning a research career in clinical oncology, with a focus on MCL.

The grant selection committee’s primary criteria include the significance and originality of the proposed study and hypothesis, the feasibility of the experiment and methodology, whether it has an appropriate and detailed statistical analysis plan, and if the research is patient oriented.

The application deadline is Jan. 7, 2020, and the award term is July 1, 2020–June 30, 2021.

Application instructions are available on the ASCO website.

[email protected]

Early-career researchers who are interested in studying mantle cell lymphoma can now apply for a $50,000 grant from the American Society of Clinical Oncology’s Conquer Cancer foundation.

The young investigator grant is for a 1-year period and the award is used to fund a project focused on clinical or translational research on the clinical biology, natural history, prevention, screening, diagnosis, therapy, or epidemiology of MCL.

The purpose of this annual award, according to ASCO, is to fund physicians during the transition from a fellowship program to a faculty appointment.

Eligible applicants must be physicians currently in the last 2 years of final subspecialty training and within 10 years of having obtained his or her medical degree. Additionally, applicants must be planning a research career in clinical oncology, with a focus on MCL.

The grant selection committee’s primary criteria include the significance and originality of the proposed study and hypothesis, the feasibility of the experiment and methodology, whether it has an appropriate and detailed statistical analysis plan, and if the research is patient oriented.

The application deadline is Jan. 7, 2020, and the award term is July 1, 2020–June 30, 2021.

Application instructions are available on the ASCO website.

[email protected]

Early-career researchers who are interested in studying mantle cell lymphoma can now apply for a $50,000 grant from the American Society of Clinical Oncology’s Conquer Cancer foundation.

The young investigator grant is for a 1-year period and the award is used to fund a project focused on clinical or translational research on the clinical biology, natural history, prevention, screening, diagnosis, therapy, or epidemiology of MCL.

The purpose of this annual award, according to ASCO, is to fund physicians during the transition from a fellowship program to a faculty appointment.

Eligible applicants must be physicians currently in the last 2 years of final subspecialty training and within 10 years of having obtained his or her medical degree. Additionally, applicants must be planning a research career in clinical oncology, with a focus on MCL.

The grant selection committee’s primary criteria include the significance and originality of the proposed study and hypothesis, the feasibility of the experiment and methodology, whether it has an appropriate and detailed statistical analysis plan, and if the research is patient oriented.

The application deadline is Jan. 7, 2020, and the award term is July 1, 2020–June 30, 2021.

Application instructions are available on the ASCO website.

[email protected]