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SAN FRANCISCO – Treatment for follicular lymphoma (FL) continues to evolve, according to a US Department of Veterans Affairs (VA) hematologist-oncologist, as second-line regimens emerge but the withdrawal of a recently approved agent complicates the picture.

“The future for our understanding and treatment of follicular lymphoma remains bright,” said Gerald Hsu, MD, PhD, of the University of California at San Francisco and the San Francisco VA Health Care System, during a presentation at the March Association of VA Hematology/Oncology (AVAHO) regional meeting on lymphoma.

By the Numbers

About 16,500 people in the US are diagnosed with FL each year. The median age of diagnosis is 64 years, and the 5-year survival rate from 2015-2021 was 89.0%, according to the National Cancer Institute. 

FL is slow-growing and indolent, Hsu said.

“[That] means that we tend to see patients who are older when they are diagnosed,” he added. “They tend to live a long time, and they’re not usually curable.”

A better understanding of the biology of FL has allowed for the development of new markers and ways of measuring residual disease, Hsu said. Additional insight may allow clinicians to identify which patients could benefit most from specific therapies.

Frontline Options

Hsu highlighted the VA Oncology Clinical Pathway for FL, which offers step-by-step guidance regarding therapy and was updated in March 2026. “It walks you through the pathway, but it’s not something that you are beholden to,” he said.

If the patient has classic FL grades 1-3A, is not at risk of transformation to aggressive lymphoma, is not in stage 1 or continuous stage lymphoma, and is indicated for therapy, the guideline recommends lenalidomide plus rituximab (R² or R-Len) or rituximab-bendamustine (R-Benda). 

“There’s a lot of data to support R-Benda,” Hsu said, pointing to a pair of studies with large numbers of patients with FL. The 2013 StiL trial tracked > 500 patients with indolent or mantle cell lymphoma (46% high risk). Those on R-Benda displayed better progression-free survival (PFS) than those taking the combination rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; hazard ratio [HR], 0.61).

In a 5-year update of the BRIGHT trial, which enrolled > 500 patients with indolent or mantle cell lymphoma (9% high risk), the R-Benda group had better PFS than patients on R-CHOP or rituximab plus cyclophosphamide, vincristine, and prednisone (HR, 0.61).

R² is a somewhat newer regimen, Hsu said. Data from the 2018 RELEVANCE study (> 1000 patients) found R² to be nonsuperior to 3 rituximab-plus-chemotherapy regimens but with a lower rate of grade 3-4 neutropenia (32% vs 50% for the other regimens). 

However, R² is “not an FDA-approved regimen in the frontline because it did not demonstrate superiority” over other treatments, Hsu said. 

Selecting the Right Therapy

Which therapy is best? It’s a bit of a wash, Hsu said. 

He noted that R², R-Benda, and another therapy that’s not yet in the VA pathway (R-CHOP) appear to be noninferior to one another, although R-Benda has the edge. R² is better regarding neutropenia risk, although it lacks FDA approval.

“I think about these 3 regimens as appropriate and good,” Hsu said. “It’s nice having 3 wonderful regimens.”

Hsu highlighted the importance of complete remission (CR) as a goal. He pointed to a 2022 analysis of > 5,200 patients that showed progression within 24 months greatly boosted the risk of death vs no-progression (HR, 3.03). Progression within 24 months also lowered estimated 5-year overall survival to 71%.

“Timing really does matter,” Hsu said. “We often worry about transformation to diffuse large B-cell in patients who relapse, particularly this early.”

Second-Line Therapy Options

Two regimens have recently achieved National Comprehensive Cancer Network Category 1 preferred status in the second-line setting, Hsu said, although neither appears in the VA pathway. 

One is tafasitamab plus R², which was shown to extend median PFS to 22.4 months vs 13.9 months for R² alone in the 2026 inMIND study (HR, 0.43), but without an overall survival benefit. 

The other therapy is epcoritamab plus R²: Data from the 2026 EPCORE FL-1 study showed an overall response rate (ORR) of 95% for the combination vs 79% for R² alone and an estimated 16-month PFS of 85.5% for the combination vs 40.2% for R².

Hsu cautioned about the adverse event profile for community infusion centers. The combination carried higher rates of grade ≥ 3 infections (33% vs 16%) and neutropenia (69% vs 42%) compared with R² alone. However, grade ≥ 3 cytokine release syndrome was absent. 

“Stay alert to higher risk for infections and neutropenia here,” Hsu said.

Beyond Second Line: Biospecifics and CAR-T

The biospecifics mosunetuzumab and epcoritamab are now FDA-approved for patients who have relapsed ≥ 2 times. Mosunetuzumab showed ORR of 78% and CR rate of 60% in a 2025 study, while epcoritamab monotherapy showed ORR of 82% and CR of 63% in a 2024 study.

Mosunetuzumab had a 2.2% rate of cytokine release syndrome and a 4.4% rate of immune effector cell-associated neurotoxicity syndrome; epcoritamab had 0% rates of both.

“Think of these 2 options as getting you to the same place, potentially, but maybe with slightly different rates of toxicity,” Hsu said. 

Meanwhile, CAR-T therapy has shown “impressive results for the right patient,” Hsu said. 

Tazemetostat Withdrawn

Hsu noted that tazemetostat, an EZH2 inhibitor that was FDA-approved for relapsed/refractory FL with EZH2 mutations and patients with FL and no satisfactory alternative options, was withdrawn from the market by Eisai in March 2026. The cause of withdrawal was increased rates of secondary hematologic malignancies. 

Meanwhile, patients enrolled in the ongoing SYMPHONY-1 trial will be switched to R².

The withdrawal was “unfortunate,” Hsu said, “but the concept is important. Identifying new targets for therapy and developing those is how we make progress.”

SAN FRANCISCO – Treatment for follicular lymphoma (FL) continues to evolve, according to a US Department of Veterans Affairs (VA) hematologist-oncologist, as second-line regimens emerge but the withdrawal of a recently approved agent complicates the picture.

“The future for our understanding and treatment of follicular lymphoma remains bright,” said Gerald Hsu, MD, PhD, of the University of California at San Francisco and the San Francisco VA Health Care System, during a presentation at the March Association of VA Hematology/Oncology (AVAHO) regional meeting on lymphoma.

By the Numbers

About 16,500 people in the US are diagnosed with FL each year. The median age of diagnosis is 64 years, and the 5-year survival rate from 2015-2021 was 89.0%, according to the National Cancer Institute. 

FL is slow-growing and indolent, Hsu said.

“[That] means that we tend to see patients who are older when they are diagnosed,” he added. “They tend to live a long time, and they’re not usually curable.”

A better understanding of the biology of FL has allowed for the development of new markers and ways of measuring residual disease, Hsu said. Additional insight may allow clinicians to identify which patients could benefit most from specific therapies.

Frontline Options

Hsu highlighted the VA Oncology Clinical Pathway for FL, which offers step-by-step guidance regarding therapy and was updated in March 2026. “It walks you through the pathway, but it’s not something that you are beholden to,” he said.

If the patient has classic FL grades 1-3A, is not at risk of transformation to aggressive lymphoma, is not in stage 1 or continuous stage lymphoma, and is indicated for therapy, the guideline recommends lenalidomide plus rituximab (R² or R-Len) or rituximab-bendamustine (R-Benda). 

“There’s a lot of data to support R-Benda,” Hsu said, pointing to a pair of studies with large numbers of patients with FL. The 2013 StiL trial tracked > 500 patients with indolent or mantle cell lymphoma (46% high risk). Those on R-Benda displayed better progression-free survival (PFS) than those taking the combination rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; hazard ratio [HR], 0.61).

In a 5-year update of the BRIGHT trial, which enrolled > 500 patients with indolent or mantle cell lymphoma (9% high risk), the R-Benda group had better PFS than patients on R-CHOP or rituximab plus cyclophosphamide, vincristine, and prednisone (HR, 0.61).

R² is a somewhat newer regimen, Hsu said. Data from the 2018 RELEVANCE study (> 1000 patients) found R² to be nonsuperior to 3 rituximab-plus-chemotherapy regimens but with a lower rate of grade 3-4 neutropenia (32% vs 50% for the other regimens). 

However, R² is “not an FDA-approved regimen in the frontline because it did not demonstrate superiority” over other treatments, Hsu said. 

Selecting the Right Therapy

Which therapy is best? It’s a bit of a wash, Hsu said. 

He noted that R², R-Benda, and another therapy that’s not yet in the VA pathway (R-CHOP) appear to be noninferior to one another, although R-Benda has the edge. R² is better regarding neutropenia risk, although it lacks FDA approval.

“I think about these 3 regimens as appropriate and good,” Hsu said. “It’s nice having 3 wonderful regimens.”

Hsu highlighted the importance of complete remission (CR) as a goal. He pointed to a 2022 analysis of > 5,200 patients that showed progression within 24 months greatly boosted the risk of death vs no-progression (HR, 3.03). Progression within 24 months also lowered estimated 5-year overall survival to 71%.

“Timing really does matter,” Hsu said. “We often worry about transformation to diffuse large B-cell in patients who relapse, particularly this early.”

Second-Line Therapy Options

Two regimens have recently achieved National Comprehensive Cancer Network Category 1 preferred status in the second-line setting, Hsu said, although neither appears in the VA pathway. 

One is tafasitamab plus R², which was shown to extend median PFS to 22.4 months vs 13.9 months for R² alone in the 2026 inMIND study (HR, 0.43), but without an overall survival benefit. 

The other therapy is epcoritamab plus R²: Data from the 2026 EPCORE FL-1 study showed an overall response rate (ORR) of 95% for the combination vs 79% for R² alone and an estimated 16-month PFS of 85.5% for the combination vs 40.2% for R².

Hsu cautioned about the adverse event profile for community infusion centers. The combination carried higher rates of grade ≥ 3 infections (33% vs 16%) and neutropenia (69% vs 42%) compared with R² alone. However, grade ≥ 3 cytokine release syndrome was absent. 

“Stay alert to higher risk for infections and neutropenia here,” Hsu said.

Beyond Second Line: Biospecifics and CAR-T

The biospecifics mosunetuzumab and epcoritamab are now FDA-approved for patients who have relapsed ≥ 2 times. Mosunetuzumab showed ORR of 78% and CR rate of 60% in a 2025 study, while epcoritamab monotherapy showed ORR of 82% and CR of 63% in a 2024 study.

Mosunetuzumab had a 2.2% rate of cytokine release syndrome and a 4.4% rate of immune effector cell-associated neurotoxicity syndrome; epcoritamab had 0% rates of both.

“Think of these 2 options as getting you to the same place, potentially, but maybe with slightly different rates of toxicity,” Hsu said. 

Meanwhile, CAR-T therapy has shown “impressive results for the right patient,” Hsu said. 

Tazemetostat Withdrawn

Hsu noted that tazemetostat, an EZH2 inhibitor that was FDA-approved for relapsed/refractory FL with EZH2 mutations and patients with FL and no satisfactory alternative options, was withdrawn from the market by Eisai in March 2026. The cause of withdrawal was increased rates of secondary hematologic malignancies. 

Meanwhile, patients enrolled in the ongoing SYMPHONY-1 trial will be switched to R².

The withdrawal was “unfortunate,” Hsu said, “but the concept is important. Identifying new targets for therapy and developing those is how we make progress.”

SAN FRANCISCO – Treatment for follicular lymphoma (FL) continues to evolve, according to a US Department of Veterans Affairs (VA) hematologist-oncologist, as second-line regimens emerge but the withdrawal of a recently approved agent complicates the picture.

“The future for our understanding and treatment of follicular lymphoma remains bright,” said Gerald Hsu, MD, PhD, of the University of California at San Francisco and the San Francisco VA Health Care System, during a presentation at the March Association of VA Hematology/Oncology (AVAHO) regional meeting on lymphoma.

By the Numbers

About 16,500 people in the US are diagnosed with FL each year. The median age of diagnosis is 64 years, and the 5-year survival rate from 2015-2021 was 89.0%, according to the National Cancer Institute. 

FL is slow-growing and indolent, Hsu said.

“[That] means that we tend to see patients who are older when they are diagnosed,” he added. “They tend to live a long time, and they’re not usually curable.”

A better understanding of the biology of FL has allowed for the development of new markers and ways of measuring residual disease, Hsu said. Additional insight may allow clinicians to identify which patients could benefit most from specific therapies.

Frontline Options

Hsu highlighted the VA Oncology Clinical Pathway for FL, which offers step-by-step guidance regarding therapy and was updated in March 2026. “It walks you through the pathway, but it’s not something that you are beholden to,” he said.

If the patient has classic FL grades 1-3A, is not at risk of transformation to aggressive lymphoma, is not in stage 1 or continuous stage lymphoma, and is indicated for therapy, the guideline recommends lenalidomide plus rituximab (R² or R-Len) or rituximab-bendamustine (R-Benda). 

“There’s a lot of data to support R-Benda,” Hsu said, pointing to a pair of studies with large numbers of patients with FL. The 2013 StiL trial tracked > 500 patients with indolent or mantle cell lymphoma (46% high risk). Those on R-Benda displayed better progression-free survival (PFS) than those taking the combination rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; hazard ratio [HR], 0.61).

In a 5-year update of the BRIGHT trial, which enrolled > 500 patients with indolent or mantle cell lymphoma (9% high risk), the R-Benda group had better PFS than patients on R-CHOP or rituximab plus cyclophosphamide, vincristine, and prednisone (HR, 0.61).

R² is a somewhat newer regimen, Hsu said. Data from the 2018 RELEVANCE study (> 1000 patients) found R² to be nonsuperior to 3 rituximab-plus-chemotherapy regimens but with a lower rate of grade 3-4 neutropenia (32% vs 50% for the other regimens). 

However, R² is “not an FDA-approved regimen in the frontline because it did not demonstrate superiority” over other treatments, Hsu said. 

Selecting the Right Therapy

Which therapy is best? It’s a bit of a wash, Hsu said. 

He noted that R², R-Benda, and another therapy that’s not yet in the VA pathway (R-CHOP) appear to be noninferior to one another, although R-Benda has the edge. R² is better regarding neutropenia risk, although it lacks FDA approval.

“I think about these 3 regimens as appropriate and good,” Hsu said. “It’s nice having 3 wonderful regimens.”

Hsu highlighted the importance of complete remission (CR) as a goal. He pointed to a 2022 analysis of > 5,200 patients that showed progression within 24 months greatly boosted the risk of death vs no-progression (HR, 3.03). Progression within 24 months also lowered estimated 5-year overall survival to 71%.

“Timing really does matter,” Hsu said. “We often worry about transformation to diffuse large B-cell in patients who relapse, particularly this early.”

Second-Line Therapy Options

Two regimens have recently achieved National Comprehensive Cancer Network Category 1 preferred status in the second-line setting, Hsu said, although neither appears in the VA pathway. 

One is tafasitamab plus R², which was shown to extend median PFS to 22.4 months vs 13.9 months for R² alone in the 2026 inMIND study (HR, 0.43), but without an overall survival benefit. 

The other therapy is epcoritamab plus R²: Data from the 2026 EPCORE FL-1 study showed an overall response rate (ORR) of 95% for the combination vs 79% for R² alone and an estimated 16-month PFS of 85.5% for the combination vs 40.2% for R².

Hsu cautioned about the adverse event profile for community infusion centers. The combination carried higher rates of grade ≥ 3 infections (33% vs 16%) and neutropenia (69% vs 42%) compared with R² alone. However, grade ≥ 3 cytokine release syndrome was absent. 

“Stay alert to higher risk for infections and neutropenia here,” Hsu said.

Beyond Second Line: Biospecifics and CAR-T

The biospecifics mosunetuzumab and epcoritamab are now FDA-approved for patients who have relapsed ≥ 2 times. Mosunetuzumab showed ORR of 78% and CR rate of 60% in a 2025 study, while epcoritamab monotherapy showed ORR of 82% and CR of 63% in a 2024 study.

Mosunetuzumab had a 2.2% rate of cytokine release syndrome and a 4.4% rate of immune effector cell-associated neurotoxicity syndrome; epcoritamab had 0% rates of both.

“Think of these 2 options as getting you to the same place, potentially, but maybe with slightly different rates of toxicity,” Hsu said. 

Meanwhile, CAR-T therapy has shown “impressive results for the right patient,” Hsu said. 

Tazemetostat Withdrawn

Hsu noted that tazemetostat, an EZH2 inhibitor that was FDA-approved for relapsed/refractory FL with EZH2 mutations and patients with FL and no satisfactory alternative options, was withdrawn from the market by Eisai in March 2026. The cause of withdrawal was increased rates of secondary hematologic malignancies. 

Meanwhile, patients enrolled in the ongoing SYMPHONY-1 trial will be switched to R².

The withdrawal was “unfortunate,” Hsu said, “but the concept is important. Identifying new targets for therapy and developing those is how we make progress.”

Male veterans are less likely than their female counterparts to be referred for follow-up questions when initial screening suggests they may be at risk of intimate partner violence (IPV), a recent large cross-sectional study finds. 

Among 67,379 patients from 131 US Department of Veterans Affairs (VA) medical centers who screened positive for risk of IPV from October 2022 through September 2023, 17.7% failed to receive a mandated secondary screen to determine whether they were in danger of lethal violence, reported Galina A. Portnoy, PhD, of VA Connecticut Healthcare System and Yale School of Medicine, et al in JAMA Network Open. The rate was higher for men with initial positive screens than women (19.3% vs 12.1%, respectively, adjusted odds ratio [AOR], 1.42, P < .001).

Overall, women who underwent secondary screening were more likely to be considered in lethal danger from IPV than men (27.9% vs 13.3%, respectively, AOR 2.29, P < .001).

“While women face higher lethality risk, men’s IPV experiences are often overlooked, underscoring the need for consistent and reliable screening practices to identify all high-risk patients and connect them to life-saving services,” Portnoy told Federal Practitioner.

“IPV is one of the strongest predictors of homicide with risk escalating over time and especially high during periods of separation.” 

“IPV among men is often underreported, unrecognized, and inadequately addressed in clinical settings,” Portnoy noted. “Men who experience IPV often face barriers to reporting—stigma, shame, and concerns about not being taken seriously.”

The VA has implemented annual screening of IPV in women of reproductive age using a modified version of the 5-question Hurt, Insult, Threaten, Scream (HITS) tool. HITS asks how often a woman’s partner had screamed, cursed, insulted, or talked down to them; threatened to harm or physically hurt them, or forced or pressured them to “have sexual contact against your will, or when you were unable to say no” in the last year.

If a patient answers yes to any of these questions, clinicians should follow up with a secondary lethality screen with 3 questions:

• Has the IPV behavior increased in frequency/severity in the past 6 months?

• Has your partner ever choked or strangled you? and

• Do you believe your partner may kill you?

The test is considered positive if a patient answers yes to any question. 

The study focused on 67,379 patients out of 1,265,115 at the VA who scored positive on HITS (mean age, 52.3 years; 23% women; 62.9% White; 8.2% Hispanic/Latino). More than two-thirds (69.0%) had a service-connected disability rating > 50%.

Portnoy said there are several possible reasons for the gender disparity in misclassification such as time constraints, discomfort, limited resources, and lack of training. Clinician bias can be a factor, too, “with IPV still widely seen as primarily a women’s issue.”

“We don’t know whether IPV screening tools work the same for men as they do for women,” Portnoy added. “The HITS tool was developed and validated using samples of women who experienced IPV, and research is needed to test whether it performs as effectively in men.”

Bethany L. Backes, PhD, associate professor and lead, Violence Against Women Faculty Cluster, University of Central Florida, Orlando, is familiar with the study findings and said in an interview that discomfort among clinicians is a significant factor in preventing follow-up IPV screening. 

“When you’re asking about this and someone says ‘yes,’ how do you respond? You just go to the next thing, the next question: ‘How many drinks have you had in the last week?’” Backes told Federal Practitioner. “We’ve talked about creating some scripts for our student health clinicians on campus about how to talk to someone when they disclose, how to then engage or provide resources.”

This is especially important because “it’s hard for people to admit that they’re experiencing this, and then when they do and it’s brushed over, they’re less likely to tell someone again,” Backes added.

C. Nadine Wathen, PhD, a professor who studies IPV at Western University in London, is also familiar with the study findings, but critiqued the HITS, calling it a “terrible name.” The tool, she said, asks about very different behaviors–being screamed or cursed, for example, and forced sexual contact,” she explained to Federal Practitioner.

“If you’re a physician and you’re asking a man, ‘Does she scream or curse at you?’ and he says ‘Yeah, she screams all the time,’ a provider might say, ‘I’m not actually thinking that he’s experiencing intimate partner violence,” Wathen said. “He might be experiencing a bad relationship.’”

That could be true, Wathen said. Couples may scream and throw things at each other, and “you probably could benefit with some couples counseling on how to have a better relationship and manage stress and anger in your relationship. But that is different than ‘intimate partner terrorism,’ where there‘s a pattern of control.”

Wathen prefers a screening tool she helped develop called the Composite Abuse Scale, which she considers more sensitive and specific than HITS. It differentiates the types of abuse that people experience, and “it also recognizes that men in relationships with other men can experience those forms of intimate terrorism, and women can also be the perpetrator of those forms.”

Recognizing that VA clinicians may not have a choice of screening tool, Wathen suggested they follow up the question about screaming and cursing question this query: “Does that make you afraid?”

The study was funded by US Department of Veterans Affairs Quality Enhancement Research Initiative and the Veterans Health Administration’s Care Management and Social Work Service via the Intimate Partner Violence Center for Implementation, Research, and Evaluation.

Portnoy has no disclosures. One author discloses relationships with the National Council on Family Relations and Military Family Research Institute. Backes and Wathen have no disclosures.

Male veterans are less likely than their female counterparts to be referred for follow-up questions when initial screening suggests they may be at risk of intimate partner violence (IPV), a recent large cross-sectional study finds. 

Among 67,379 patients from 131 US Department of Veterans Affairs (VA) medical centers who screened positive for risk of IPV from October 2022 through September 2023, 17.7% failed to receive a mandated secondary screen to determine whether they were in danger of lethal violence, reported Galina A. Portnoy, PhD, of VA Connecticut Healthcare System and Yale School of Medicine, et al in JAMA Network Open. The rate was higher for men with initial positive screens than women (19.3% vs 12.1%, respectively, adjusted odds ratio [AOR], 1.42, P < .001).

Overall, women who underwent secondary screening were more likely to be considered in lethal danger from IPV than men (27.9% vs 13.3%, respectively, AOR 2.29, P < .001).

“While women face higher lethality risk, men’s IPV experiences are often overlooked, underscoring the need for consistent and reliable screening practices to identify all high-risk patients and connect them to life-saving services,” Portnoy told Federal Practitioner.

“IPV is one of the strongest predictors of homicide with risk escalating over time and especially high during periods of separation.” 

“IPV among men is often underreported, unrecognized, and inadequately addressed in clinical settings,” Portnoy noted. “Men who experience IPV often face barriers to reporting—stigma, shame, and concerns about not being taken seriously.”

The VA has implemented annual screening of IPV in women of reproductive age using a modified version of the 5-question Hurt, Insult, Threaten, Scream (HITS) tool. HITS asks how often a woman’s partner had screamed, cursed, insulted, or talked down to them; threatened to harm or physically hurt them, or forced or pressured them to “have sexual contact against your will, or when you were unable to say no” in the last year.

If a patient answers yes to any of these questions, clinicians should follow up with a secondary lethality screen with 3 questions:

• Has the IPV behavior increased in frequency/severity in the past 6 months?

• Has your partner ever choked or strangled you? and

• Do you believe your partner may kill you?

The test is considered positive if a patient answers yes to any question. 

The study focused on 67,379 patients out of 1,265,115 at the VA who scored positive on HITS (mean age, 52.3 years; 23% women; 62.9% White; 8.2% Hispanic/Latino). More than two-thirds (69.0%) had a service-connected disability rating > 50%.

Portnoy said there are several possible reasons for the gender disparity in misclassification such as time constraints, discomfort, limited resources, and lack of training. Clinician bias can be a factor, too, “with IPV still widely seen as primarily a women’s issue.”

“We don’t know whether IPV screening tools work the same for men as they do for women,” Portnoy added. “The HITS tool was developed and validated using samples of women who experienced IPV, and research is needed to test whether it performs as effectively in men.”

Bethany L. Backes, PhD, associate professor and lead, Violence Against Women Faculty Cluster, University of Central Florida, Orlando, is familiar with the study findings and said in an interview that discomfort among clinicians is a significant factor in preventing follow-up IPV screening. 

“When you’re asking about this and someone says ‘yes,’ how do you respond? You just go to the next thing, the next question: ‘How many drinks have you had in the last week?’” Backes told Federal Practitioner. “We’ve talked about creating some scripts for our student health clinicians on campus about how to talk to someone when they disclose, how to then engage or provide resources.”

This is especially important because “it’s hard for people to admit that they’re experiencing this, and then when they do and it’s brushed over, they’re less likely to tell someone again,” Backes added.

C. Nadine Wathen, PhD, a professor who studies IPV at Western University in London, is also familiar with the study findings, but critiqued the HITS, calling it a “terrible name.” The tool, she said, asks about very different behaviors–being screamed or cursed, for example, and forced sexual contact,” she explained to Federal Practitioner.

“If you’re a physician and you’re asking a man, ‘Does she scream or curse at you?’ and he says ‘Yeah, she screams all the time,’ a provider might say, ‘I’m not actually thinking that he’s experiencing intimate partner violence,” Wathen said. “He might be experiencing a bad relationship.’”

That could be true, Wathen said. Couples may scream and throw things at each other, and “you probably could benefit with some couples counseling on how to have a better relationship and manage stress and anger in your relationship. But that is different than ‘intimate partner terrorism,’ where there‘s a pattern of control.”

Wathen prefers a screening tool she helped develop called the Composite Abuse Scale, which she considers more sensitive and specific than HITS. It differentiates the types of abuse that people experience, and “it also recognizes that men in relationships with other men can experience those forms of intimate terrorism, and women can also be the perpetrator of those forms.”

Recognizing that VA clinicians may not have a choice of screening tool, Wathen suggested they follow up the question about screaming and cursing question this query: “Does that make you afraid?”

The study was funded by US Department of Veterans Affairs Quality Enhancement Research Initiative and the Veterans Health Administration’s Care Management and Social Work Service via the Intimate Partner Violence Center for Implementation, Research, and Evaluation.

Portnoy has no disclosures. One author discloses relationships with the National Council on Family Relations and Military Family Research Institute. Backes and Wathen have no disclosures.

Male veterans are less likely than their female counterparts to be referred for follow-up questions when initial screening suggests they may be at risk of intimate partner violence (IPV), a recent large cross-sectional study finds. 

Among 67,379 patients from 131 US Department of Veterans Affairs (VA) medical centers who screened positive for risk of IPV from October 2022 through September 2023, 17.7% failed to receive a mandated secondary screen to determine whether they were in danger of lethal violence, reported Galina A. Portnoy, PhD, of VA Connecticut Healthcare System and Yale School of Medicine, et al in JAMA Network Open. The rate was higher for men with initial positive screens than women (19.3% vs 12.1%, respectively, adjusted odds ratio [AOR], 1.42, P < .001).

Overall, women who underwent secondary screening were more likely to be considered in lethal danger from IPV than men (27.9% vs 13.3%, respectively, AOR 2.29, P < .001).

“While women face higher lethality risk, men’s IPV experiences are often overlooked, underscoring the need for consistent and reliable screening practices to identify all high-risk patients and connect them to life-saving services,” Portnoy told Federal Practitioner.

“IPV is one of the strongest predictors of homicide with risk escalating over time and especially high during periods of separation.” 

“IPV among men is often underreported, unrecognized, and inadequately addressed in clinical settings,” Portnoy noted. “Men who experience IPV often face barriers to reporting—stigma, shame, and concerns about not being taken seriously.”

The VA has implemented annual screening of IPV in women of reproductive age using a modified version of the 5-question Hurt, Insult, Threaten, Scream (HITS) tool. HITS asks how often a woman’s partner had screamed, cursed, insulted, or talked down to them; threatened to harm or physically hurt them, or forced or pressured them to “have sexual contact against your will, or when you were unable to say no” in the last year.

If a patient answers yes to any of these questions, clinicians should follow up with a secondary lethality screen with 3 questions:

• Has the IPV behavior increased in frequency/severity in the past 6 months?

• Has your partner ever choked or strangled you? and

• Do you believe your partner may kill you?

The test is considered positive if a patient answers yes to any question. 

The study focused on 67,379 patients out of 1,265,115 at the VA who scored positive on HITS (mean age, 52.3 years; 23% women; 62.9% White; 8.2% Hispanic/Latino). More than two-thirds (69.0%) had a service-connected disability rating > 50%.

Portnoy said there are several possible reasons for the gender disparity in misclassification such as time constraints, discomfort, limited resources, and lack of training. Clinician bias can be a factor, too, “with IPV still widely seen as primarily a women’s issue.”

“We don’t know whether IPV screening tools work the same for men as they do for women,” Portnoy added. “The HITS tool was developed and validated using samples of women who experienced IPV, and research is needed to test whether it performs as effectively in men.”

Bethany L. Backes, PhD, associate professor and lead, Violence Against Women Faculty Cluster, University of Central Florida, Orlando, is familiar with the study findings and said in an interview that discomfort among clinicians is a significant factor in preventing follow-up IPV screening. 

“When you’re asking about this and someone says ‘yes,’ how do you respond? You just go to the next thing, the next question: ‘How many drinks have you had in the last week?’” Backes told Federal Practitioner. “We’ve talked about creating some scripts for our student health clinicians on campus about how to talk to someone when they disclose, how to then engage or provide resources.”

This is especially important because “it’s hard for people to admit that they’re experiencing this, and then when they do and it’s brushed over, they’re less likely to tell someone again,” Backes added.

C. Nadine Wathen, PhD, a professor who studies IPV at Western University in London, is also familiar with the study findings, but critiqued the HITS, calling it a “terrible name.” The tool, she said, asks about very different behaviors–being screamed or cursed, for example, and forced sexual contact,” she explained to Federal Practitioner.

“If you’re a physician and you’re asking a man, ‘Does she scream or curse at you?’ and he says ‘Yeah, she screams all the time,’ a provider might say, ‘I’m not actually thinking that he’s experiencing intimate partner violence,” Wathen said. “He might be experiencing a bad relationship.’”

That could be true, Wathen said. Couples may scream and throw things at each other, and “you probably could benefit with some couples counseling on how to have a better relationship and manage stress and anger in your relationship. But that is different than ‘intimate partner terrorism,’ where there‘s a pattern of control.”

Wathen prefers a screening tool she helped develop called the Composite Abuse Scale, which she considers more sensitive and specific than HITS. It differentiates the types of abuse that people experience, and “it also recognizes that men in relationships with other men can experience those forms of intimate terrorism, and women can also be the perpetrator of those forms.”

Recognizing that VA clinicians may not have a choice of screening tool, Wathen suggested they follow up the question about screaming and cursing question this query: “Does that make you afraid?”

The study was funded by US Department of Veterans Affairs Quality Enhancement Research Initiative and the Veterans Health Administration’s Care Management and Social Work Service via the Intimate Partner Violence Center for Implementation, Research, and Evaluation.

Portnoy has no disclosures. One author discloses relationships with the National Council on Family Relations and Military Family Research Institute. Backes and Wathen have no disclosures.

Though end-of-life care for veterans with chronic obstructive pulmonary disease (COPD) in the US Department of Veterans Affairs (VA) has become more prevalent in recent years, a recent retrospective cohort study found that most patients do not receive palliative care or inpatient VA hospice over the past year of life, with rates lower than for other terminal illnesses. 

Among 332,770 decedents traced from 2010 through 2020, only 16.8% received either palliative or inpatient hospice care in the year before their death. The median time between their first palliative care appointment and death was 46 days, reported pulmonologist Natalia Smirnova, MD, assistant professor of medicine, Emory School of Medicine, Atlanta, et al in CHEST Pulmonary. 

A total of 15.9% of the decedents received inpatient hospice care from the VA. 

“These findings point to an opportunity to improve access to palliative care and hospice services for veterans with COPD, including earlier identification of need and stronger access pathways across care settings,” Smirnova told Federal Practitioner.

COPD Common Among Vets

An estimated 8%-19% of US veterans have COPD, higher than the estimated rate of 6% in adults from the general population. The condition is believed to be underdiagnosed in veterans. 

“Palliative care should be integrated early into routine care, when symptoms start,” Kathleen Lindell, PhD, RN, associate professor and chair, Palliative Care Health, School of Nursing, Medical University of South Carolina, Charleston, explained in a Federal Practitioner interview. “COPD is a serious respiratory illness, and patients experience progressively debilitating dyspnea or shortness of breath, frequent hospitalizations. And they frequently experience high rates of anxiety and depression,” 

Lindell is familiar with the study findings but didn’t take part in the research. 

“Early palliative care,” she said, “addresses symptom management and advance care planning to reduce suffering and ensure what matters most to the patient as the disease progresses.”

Smirnova noted that “hospice is a related but distinct service for veterans with a terminal condition, generally when life expectancy is < 6 months and the veteran is no longer seeking treatment other than palliative care.”

The study analyzed electronic health records and patterns of palliative and hospice care in the year before death. The 332,770 patients were mostly male (98.1%) and White (81.0%). Many had comorbidities such as congestive heart failure (30.0%), depression (26.0%), coronary artery disease (25.5%), anxiety (13.4%), and lung cancer (12.1%).

Researchers found that palliative care was mostly (61.6% of encounters) delivered in the inpatient setting, where it occurred a median 30 days before death. In the outpatient setting, it began a median of 71 days before death. 

From 2010 through 2020, the prevalence of palliative care increased from 10.4% to 16.0%, and the prevalence of VA inpatient hospice care increased from 15.0% to 18.0%. Some veterans may have received hospice services in other settings; in-home hospice is common.

Who is More Likely to Receive Palliative Care?

Black patients (adjusted odds ratio [AOR], 1.21), Latino/Hispanic ethnicity (AOR, 1.22), patients with housing instability (AOR, 1.38) and who were underweight (AOR, 1.75) were linked to more palliative care use. Black patients were especially likely to get inpatient palliative care, a fact that “may, in part, be driven by increased care intensity at the end of life, as has been demonstrated in prior studies,” the authors noted.

Marriage (AOR, 0.88) was linked to less palliative care use, while patients with lung cancer were especially likely to receive it (AOR, 2.48). There were similar differences in use of hospice care apart from higher use for Black patients. 

Smirnova said the study was not designed to determine the causes of patterns in palliative care use. However, important factors appear to include hospitalization, comorbidities, and access to care at health care sites. (Usage rates were lower at rural centers and higher at more complex centers.)

COPD vs Other Terminal Diseases

“The modest increases in utilization of palliative care and VA inpatient hospice from 2010 to 2020 align with previous work [research] in inpatients with COPD and heart failure,” the researchers wrote, “possibly reflecting the effect of international professional society guidelines, increased acceptance of palliative care, improvements related to VA end-of-life care and life-sustaining treatment decisions initiatives, and increases in the specialist palliative care workforce.”

Still, there appears to be a major discrepancy regarding the use of palliative care for COPD within the VA compared with other diseases. A study of data from 2014 through 2017 found that for patients with several comorbidities—including COPD, heart failure, cancer, and dementia—inpatient palliative care was introduced a median of 58 days before death and outpatient care 160 days before death. 

“This suggests that veterans with COPD receive palliative care later than those with other serious illnesses,” the authors argued. 

Don’t Wait for the ‘Right Time’

Sarah Miller, PhD, RN, associate professor, and assistant dean, PhD Nursing Science Program, School of Nursing, Medical University of South Carolina, Charleston, praised the study in an interview and noted that uncertainty about the “right time” to refer patients to palliative care could play a role in the findings. Miller is familiar with the study but did not participate in the research.

Lindell, the chair of Palliative Care Health, agreed.

“With COPD—a chronic, progressive disease—decline can be gradual, which makes it difficult to identify a clear transition point,” Lindell told Federal Practitioner. “This has contributed to many palliative referrals happening only when patients are clearly deteriorating or nearing the end of life. But palliative care should not be introduced reactively; it should be integrated early, alongside disease-directed treatment.”

For her part, Miller noted that “many veterans with COPD are navigating complex comorbidities and fragmented care across settings. Diseases like COPD don’t follow a predictable path, so referrals don’t always happen like they should.”

Moving forward, “if symptoms are present, early palliative care is appropriate,” Lindell said. These conversations should happen early and over time.

“The VA should prioritize early referral and access to palliative care for patients with COPD to provide the best care for these individuals.”

No study funding was reported. Smirnova discloses relationships with the CHEST Foundation and National Heart, Lung, and Blood Institute. Other authors disclose relationships with various grantors. 

Miller discloses a relationship with AstraZeneca. Lindell discloses relationships with Boehringer Ingelheim and Heart & Lung: The Journal of Acute and Critical Care. 

Though end-of-life care for veterans with chronic obstructive pulmonary disease (COPD) in the US Department of Veterans Affairs (VA) has become more prevalent in recent years, a recent retrospective cohort study found that most patients do not receive palliative care or inpatient VA hospice over the past year of life, with rates lower than for other terminal illnesses. 

Among 332,770 decedents traced from 2010 through 2020, only 16.8% received either palliative or inpatient hospice care in the year before their death. The median time between their first palliative care appointment and death was 46 days, reported pulmonologist Natalia Smirnova, MD, assistant professor of medicine, Emory School of Medicine, Atlanta, et al in CHEST Pulmonary. 

A total of 15.9% of the decedents received inpatient hospice care from the VA. 

“These findings point to an opportunity to improve access to palliative care and hospice services for veterans with COPD, including earlier identification of need and stronger access pathways across care settings,” Smirnova told Federal Practitioner.

COPD Common Among Vets

An estimated 8%-19% of US veterans have COPD, higher than the estimated rate of 6% in adults from the general population. The condition is believed to be underdiagnosed in veterans. 

“Palliative care should be integrated early into routine care, when symptoms start,” Kathleen Lindell, PhD, RN, associate professor and chair, Palliative Care Health, School of Nursing, Medical University of South Carolina, Charleston, explained in a Federal Practitioner interview. “COPD is a serious respiratory illness, and patients experience progressively debilitating dyspnea or shortness of breath, frequent hospitalizations. And they frequently experience high rates of anxiety and depression,” 

Lindell is familiar with the study findings but didn’t take part in the research. 

“Early palliative care,” she said, “addresses symptom management and advance care planning to reduce suffering and ensure what matters most to the patient as the disease progresses.”

Smirnova noted that “hospice is a related but distinct service for veterans with a terminal condition, generally when life expectancy is < 6 months and the veteran is no longer seeking treatment other than palliative care.”

The study analyzed electronic health records and patterns of palliative and hospice care in the year before death. The 332,770 patients were mostly male (98.1%) and White (81.0%). Many had comorbidities such as congestive heart failure (30.0%), depression (26.0%), coronary artery disease (25.5%), anxiety (13.4%), and lung cancer (12.1%).

Researchers found that palliative care was mostly (61.6% of encounters) delivered in the inpatient setting, where it occurred a median 30 days before death. In the outpatient setting, it began a median of 71 days before death. 

From 2010 through 2020, the prevalence of palliative care increased from 10.4% to 16.0%, and the prevalence of VA inpatient hospice care increased from 15.0% to 18.0%. Some veterans may have received hospice services in other settings; in-home hospice is common.

Who is More Likely to Receive Palliative Care?

Black patients (adjusted odds ratio [AOR], 1.21), Latino/Hispanic ethnicity (AOR, 1.22), patients with housing instability (AOR, 1.38) and who were underweight (AOR, 1.75) were linked to more palliative care use. Black patients were especially likely to get inpatient palliative care, a fact that “may, in part, be driven by increased care intensity at the end of life, as has been demonstrated in prior studies,” the authors noted.

Marriage (AOR, 0.88) was linked to less palliative care use, while patients with lung cancer were especially likely to receive it (AOR, 2.48). There were similar differences in use of hospice care apart from higher use for Black patients. 

Smirnova said the study was not designed to determine the causes of patterns in palliative care use. However, important factors appear to include hospitalization, comorbidities, and access to care at health care sites. (Usage rates were lower at rural centers and higher at more complex centers.)

COPD vs Other Terminal Diseases

“The modest increases in utilization of palliative care and VA inpatient hospice from 2010 to 2020 align with previous work [research] in inpatients with COPD and heart failure,” the researchers wrote, “possibly reflecting the effect of international professional society guidelines, increased acceptance of palliative care, improvements related to VA end-of-life care and life-sustaining treatment decisions initiatives, and increases in the specialist palliative care workforce.”

Still, there appears to be a major discrepancy regarding the use of palliative care for COPD within the VA compared with other diseases. A study of data from 2014 through 2017 found that for patients with several comorbidities—including COPD, heart failure, cancer, and dementia—inpatient palliative care was introduced a median of 58 days before death and outpatient care 160 days before death. 

“This suggests that veterans with COPD receive palliative care later than those with other serious illnesses,” the authors argued. 

Don’t Wait for the ‘Right Time’

Sarah Miller, PhD, RN, associate professor, and assistant dean, PhD Nursing Science Program, School of Nursing, Medical University of South Carolina, Charleston, praised the study in an interview and noted that uncertainty about the “right time” to refer patients to palliative care could play a role in the findings. Miller is familiar with the study but did not participate in the research.

Lindell, the chair of Palliative Care Health, agreed.

“With COPD—a chronic, progressive disease—decline can be gradual, which makes it difficult to identify a clear transition point,” Lindell told Federal Practitioner. “This has contributed to many palliative referrals happening only when patients are clearly deteriorating or nearing the end of life. But palliative care should not be introduced reactively; it should be integrated early, alongside disease-directed treatment.”

For her part, Miller noted that “many veterans with COPD are navigating complex comorbidities and fragmented care across settings. Diseases like COPD don’t follow a predictable path, so referrals don’t always happen like they should.”

Moving forward, “if symptoms are present, early palliative care is appropriate,” Lindell said. These conversations should happen early and over time.

“The VA should prioritize early referral and access to palliative care for patients with COPD to provide the best care for these individuals.”

No study funding was reported. Smirnova discloses relationships with the CHEST Foundation and National Heart, Lung, and Blood Institute. Other authors disclose relationships with various grantors. 

Miller discloses a relationship with AstraZeneca. Lindell discloses relationships with Boehringer Ingelheim and Heart & Lung: The Journal of Acute and Critical Care. 

Though end-of-life care for veterans with chronic obstructive pulmonary disease (COPD) in the US Department of Veterans Affairs (VA) has become more prevalent in recent years, a recent retrospective cohort study found that most patients do not receive palliative care or inpatient VA hospice over the past year of life, with rates lower than for other terminal illnesses. 

Among 332,770 decedents traced from 2010 through 2020, only 16.8% received either palliative or inpatient hospice care in the year before their death. The median time between their first palliative care appointment and death was 46 days, reported pulmonologist Natalia Smirnova, MD, assistant professor of medicine, Emory School of Medicine, Atlanta, et al in CHEST Pulmonary. 

A total of 15.9% of the decedents received inpatient hospice care from the VA. 

“These findings point to an opportunity to improve access to palliative care and hospice services for veterans with COPD, including earlier identification of need and stronger access pathways across care settings,” Smirnova told Federal Practitioner.

COPD Common Among Vets

An estimated 8%-19% of US veterans have COPD, higher than the estimated rate of 6% in adults from the general population. The condition is believed to be underdiagnosed in veterans. 

“Palliative care should be integrated early into routine care, when symptoms start,” Kathleen Lindell, PhD, RN, associate professor and chair, Palliative Care Health, School of Nursing, Medical University of South Carolina, Charleston, explained in a Federal Practitioner interview. “COPD is a serious respiratory illness, and patients experience progressively debilitating dyspnea or shortness of breath, frequent hospitalizations. And they frequently experience high rates of anxiety and depression,” 

Lindell is familiar with the study findings but didn’t take part in the research. 

“Early palliative care,” she said, “addresses symptom management and advance care planning to reduce suffering and ensure what matters most to the patient as the disease progresses.”

Smirnova noted that “hospice is a related but distinct service for veterans with a terminal condition, generally when life expectancy is < 6 months and the veteran is no longer seeking treatment other than palliative care.”

The study analyzed electronic health records and patterns of palliative and hospice care in the year before death. The 332,770 patients were mostly male (98.1%) and White (81.0%). Many had comorbidities such as congestive heart failure (30.0%), depression (26.0%), coronary artery disease (25.5%), anxiety (13.4%), and lung cancer (12.1%).

Researchers found that palliative care was mostly (61.6% of encounters) delivered in the inpatient setting, where it occurred a median 30 days before death. In the outpatient setting, it began a median of 71 days before death. 

From 2010 through 2020, the prevalence of palliative care increased from 10.4% to 16.0%, and the prevalence of VA inpatient hospice care increased from 15.0% to 18.0%. Some veterans may have received hospice services in other settings; in-home hospice is common.

Who is More Likely to Receive Palliative Care?

Black patients (adjusted odds ratio [AOR], 1.21), Latino/Hispanic ethnicity (AOR, 1.22), patients with housing instability (AOR, 1.38) and who were underweight (AOR, 1.75) were linked to more palliative care use. Black patients were especially likely to get inpatient palliative care, a fact that “may, in part, be driven by increased care intensity at the end of life, as has been demonstrated in prior studies,” the authors noted.

Marriage (AOR, 0.88) was linked to less palliative care use, while patients with lung cancer were especially likely to receive it (AOR, 2.48). There were similar differences in use of hospice care apart from higher use for Black patients. 

Smirnova said the study was not designed to determine the causes of patterns in palliative care use. However, important factors appear to include hospitalization, comorbidities, and access to care at health care sites. (Usage rates were lower at rural centers and higher at more complex centers.)

COPD vs Other Terminal Diseases

“The modest increases in utilization of palliative care and VA inpatient hospice from 2010 to 2020 align with previous work [research] in inpatients with COPD and heart failure,” the researchers wrote, “possibly reflecting the effect of international professional society guidelines, increased acceptance of palliative care, improvements related to VA end-of-life care and life-sustaining treatment decisions initiatives, and increases in the specialist palliative care workforce.”

Still, there appears to be a major discrepancy regarding the use of palliative care for COPD within the VA compared with other diseases. A study of data from 2014 through 2017 found that for patients with several comorbidities—including COPD, heart failure, cancer, and dementia—inpatient palliative care was introduced a median of 58 days before death and outpatient care 160 days before death. 

“This suggests that veterans with COPD receive palliative care later than those with other serious illnesses,” the authors argued. 

Don’t Wait for the ‘Right Time’

Sarah Miller, PhD, RN, associate professor, and assistant dean, PhD Nursing Science Program, School of Nursing, Medical University of South Carolina, Charleston, praised the study in an interview and noted that uncertainty about the “right time” to refer patients to palliative care could play a role in the findings. Miller is familiar with the study but did not participate in the research.

Lindell, the chair of Palliative Care Health, agreed.

“With COPD—a chronic, progressive disease—decline can be gradual, which makes it difficult to identify a clear transition point,” Lindell told Federal Practitioner. “This has contributed to many palliative referrals happening only when patients are clearly deteriorating or nearing the end of life. But palliative care should not be introduced reactively; it should be integrated early, alongside disease-directed treatment.”

For her part, Miller noted that “many veterans with COPD are navigating complex comorbidities and fragmented care across settings. Diseases like COPD don’t follow a predictable path, so referrals don’t always happen like they should.”

Moving forward, “if symptoms are present, early palliative care is appropriate,” Lindell said. These conversations should happen early and over time.

“The VA should prioritize early referral and access to palliative care for patients with COPD to provide the best care for these individuals.”

No study funding was reported. Smirnova discloses relationships with the CHEST Foundation and National Heart, Lung, and Blood Institute. Other authors disclose relationships with various grantors. 

Miller discloses a relationship with AstraZeneca. Lindell discloses relationships with Boehringer Ingelheim and Heart & Lung: The Journal of Acute and Critical Care. 

Metabolic dysfunction-associated steatotic liver disease (MASLD) has surpassed hepatitis C virus (HCV) infection as the leading cause of cirrhosis among veterans, according to a recently published retrospective analysis. This trend suggests a major shift in the causes of chronic liver disease due to effective HCV therapy and the continued rise of obesity and diabetes.

The analysis also found an increase in overall cirrhosis among veterans despite a massive dropoff in HCV. The data also hint that alcohol-related cases are on the rise.

Among new cirrhosis cases in the US Department of Veterans Affairs (VA) tracked annually from 2014 to 2023, the percentage due to HCV alone fell from 36.1% to 8.7%, while cases linked to MASLD rose from 26.8% to 41.0%, Pedro Ochoa-Allemant, MD, MSCE, a clinical fellow in advanced/transplant hepatology at the University of Pennsylvania, et al, reported in the American Journal of Gastroenterology.

Cases due to alcohol use rose from 12.5% to 22.5%; those linked to metabolic dysfunction and alcohol use combined increased from 8.1% to 16.6%.

“This shift represents a major public health challenge,” Ochoa-Allemant told Federal Practitioner, noting that metabolic- and alcohol-related forms of cirrhosis require long-term care, unlike HCV, which has a cure.

“For this reason, we should move towards better strategies for early identification, risk stratification, and prevention, particularly in primary care where most patients are seen,” he said.

New Nomenclature, Rising Cases

Ochoa-Allemant et al launched the study to better understand the etiology of cirrhosis in light of the lack of new population-based research using recently revised steatotic liver disease nomenclature. In 2023, liver specialists removed “nonalcoholic fatty liver disease” and “nonalcoholic steatohepatitis” from the taxonomy, dismissing them as “exclusionary, negative” terms that “used potentially stigmatizing language.”

The study analyzed the Veterans Outcomes and Costs Associated with Liver Disease cohort, which includes > 1300 Veterans Health Administration (VHA) facilities.

In 2014, 0.84% of 5.7 million veterans who were actively treated at the VHA had cirrhosis. The prevalence grew to 1.29% of 6.0 million veterans in 2023, reflecting a direct increase in overall cases.

Hepatitis C Declines, Obesity Rises

Ochoa-Allemant attributed the changing picture of cirrhosis to available antiviral cures for HCV and the rising burden of obesity and diabetes in the general population.

“This shift means that prevention of cirrhosis is no longer primarily about treating HCV infection, but it now requires our focus on managing cardiometabolic risk factors and increased alcohol use,” he said.

He also noted that the study reported information on new cases of cirrhosis vs deaths that suggests MASLD rates are stabilizing while cases related to alcohol continue to rise.

A March 2026 study in The Lancet Gastroenterology & Hepatology reported similar trends. The analysis of 41,100 US adults with cirrhosis from 1988 to 2023 identified a significant increase in the prevalence of MASLD among those with steatotic liver disease (12.69% to 28.16%)

Alcohol-Related Cases May Be Undercounted

Elliot B. Tapper, MD, research professor of hepatology and associate professor of internal medicine at the University of Michigan Medical School, told Federal Practitioner that the findings are “striking, but not entirely unexpected given the obesity and diabetes epidemics.”

Tapper is familiar with the study but did not participate in it, added that the impact of alcohol may be even larger due to misclassification. The figures regarding alcohol-related cases “should probably be interpreted as a floor rather than a ceiling,” he said in an interview.

Moving forward, Tapper said “multidisciplinary collaboration with endocrinology, addiction medicine, and primary care is no longer optional. I would go further. Hepatologists cannot defer management to others.”

New Therapies for Metabolic-Related Liver Disease

Heather M. Patton, MD, chief of the Gastrointestinal Section at VA San Diego Healthcare System and clinical professor of medicine at the University of California at San Diego, told Federal Practitioner that “it is essential to ensure that patients with chronic HCV infection and advanced fibrosis continue to receive appropriate care following HCV cure, inclusive of liver cancer screening."

As for cases related to metabolic syndrome, Patton – who also is familiar with the study findings but did not take part – highlighted the role of newly approved therapies for metabolic-associated steatohepatitis. Most recently, the US Food and Drug Administration approved the GLP-1 agonist semaglutide for the condition.

The treatments represent “a tremendous opportunity to decrease incident cirrhosis,” Patton said in an interview. She also noted that primary care physicians and endocrinologists should recognize that “metabolic health is a major risk factor for liver disease, and utilizing liver health screening tools such as the FIB-4 score has the opportunity to save lives."

The authors of the new study cited limitations regarding generalizability such as male predominance and higher psychosocial comorbidity. They also noted that the decline in HCV-related cirrhosis probably occurred earlier in the VA system than elsewhere due to “greater identification and access to antiviral therapy.”

They also noted that attribution of cases to alcohol may be underestimated due to self-reporting.

No study funding is reported. Ochoa-Allemant discloses a relationship with the National Institutes of Health. Other authors disclose relationships with the National Institutes of Health, Grifols, National Institute on Aging, and the VA. Tapper discloses relationships with Madrigal, Resolution, Korro, Tortugas, Satellite, Bausch, Iota, and Mirum. Patton has no disclosures.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has surpassed hepatitis C virus (HCV) infection as the leading cause of cirrhosis among veterans, according to a recently published retrospective analysis. This trend suggests a major shift in the causes of chronic liver disease due to effective HCV therapy and the continued rise of obesity and diabetes.

The analysis also found an increase in overall cirrhosis among veterans despite a massive dropoff in HCV. The data also hint that alcohol-related cases are on the rise.

Among new cirrhosis cases in the US Department of Veterans Affairs (VA) tracked annually from 2014 to 2023, the percentage due to HCV alone fell from 36.1% to 8.7%, while cases linked to MASLD rose from 26.8% to 41.0%, Pedro Ochoa-Allemant, MD, MSCE, a clinical fellow in advanced/transplant hepatology at the University of Pennsylvania, et al, reported in the American Journal of Gastroenterology.

Cases due to alcohol use rose from 12.5% to 22.5%; those linked to metabolic dysfunction and alcohol use combined increased from 8.1% to 16.6%.

“This shift represents a major public health challenge,” Ochoa-Allemant told Federal Practitioner, noting that metabolic- and alcohol-related forms of cirrhosis require long-term care, unlike HCV, which has a cure.

“For this reason, we should move towards better strategies for early identification, risk stratification, and prevention, particularly in primary care where most patients are seen,” he said.

New Nomenclature, Rising Cases

Ochoa-Allemant et al launched the study to better understand the etiology of cirrhosis in light of the lack of new population-based research using recently revised steatotic liver disease nomenclature. In 2023, liver specialists removed “nonalcoholic fatty liver disease” and “nonalcoholic steatohepatitis” from the taxonomy, dismissing them as “exclusionary, negative” terms that “used potentially stigmatizing language.”

The study analyzed the Veterans Outcomes and Costs Associated with Liver Disease cohort, which includes > 1300 Veterans Health Administration (VHA) facilities.

In 2014, 0.84% of 5.7 million veterans who were actively treated at the VHA had cirrhosis. The prevalence grew to 1.29% of 6.0 million veterans in 2023, reflecting a direct increase in overall cases.

Hepatitis C Declines, Obesity Rises

Ochoa-Allemant attributed the changing picture of cirrhosis to available antiviral cures for HCV and the rising burden of obesity and diabetes in the general population.

“This shift means that prevention of cirrhosis is no longer primarily about treating HCV infection, but it now requires our focus on managing cardiometabolic risk factors and increased alcohol use,” he said.

He also noted that the study reported information on new cases of cirrhosis vs deaths that suggests MASLD rates are stabilizing while cases related to alcohol continue to rise.

A March 2026 study in The Lancet Gastroenterology & Hepatology reported similar trends. The analysis of 41,100 US adults with cirrhosis from 1988 to 2023 identified a significant increase in the prevalence of MASLD among those with steatotic liver disease (12.69% to 28.16%)

Alcohol-Related Cases May Be Undercounted

Elliot B. Tapper, MD, research professor of hepatology and associate professor of internal medicine at the University of Michigan Medical School, told Federal Practitioner that the findings are “striking, but not entirely unexpected given the obesity and diabetes epidemics.”

Tapper is familiar with the study but did not participate in it, added that the impact of alcohol may be even larger due to misclassification. The figures regarding alcohol-related cases “should probably be interpreted as a floor rather than a ceiling,” he said in an interview.

Moving forward, Tapper said “multidisciplinary collaboration with endocrinology, addiction medicine, and primary care is no longer optional. I would go further. Hepatologists cannot defer management to others.”

New Therapies for Metabolic-Related Liver Disease

Heather M. Patton, MD, chief of the Gastrointestinal Section at VA San Diego Healthcare System and clinical professor of medicine at the University of California at San Diego, told Federal Practitioner that “it is essential to ensure that patients with chronic HCV infection and advanced fibrosis continue to receive appropriate care following HCV cure, inclusive of liver cancer screening."

As for cases related to metabolic syndrome, Patton – who also is familiar with the study findings but did not take part – highlighted the role of newly approved therapies for metabolic-associated steatohepatitis. Most recently, the US Food and Drug Administration approved the GLP-1 agonist semaglutide for the condition.

The treatments represent “a tremendous opportunity to decrease incident cirrhosis,” Patton said in an interview. She also noted that primary care physicians and endocrinologists should recognize that “metabolic health is a major risk factor for liver disease, and utilizing liver health screening tools such as the FIB-4 score has the opportunity to save lives."

The authors of the new study cited limitations regarding generalizability such as male predominance and higher psychosocial comorbidity. They also noted that the decline in HCV-related cirrhosis probably occurred earlier in the VA system than elsewhere due to “greater identification and access to antiviral therapy.”

They also noted that attribution of cases to alcohol may be underestimated due to self-reporting.

No study funding is reported. Ochoa-Allemant discloses a relationship with the National Institutes of Health. Other authors disclose relationships with the National Institutes of Health, Grifols, National Institute on Aging, and the VA. Tapper discloses relationships with Madrigal, Resolution, Korro, Tortugas, Satellite, Bausch, Iota, and Mirum. Patton has no disclosures.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has surpassed hepatitis C virus (HCV) infection as the leading cause of cirrhosis among veterans, according to a recently published retrospective analysis. This trend suggests a major shift in the causes of chronic liver disease due to effective HCV therapy and the continued rise of obesity and diabetes.

The analysis also found an increase in overall cirrhosis among veterans despite a massive dropoff in HCV. The data also hint that alcohol-related cases are on the rise.

Among new cirrhosis cases in the US Department of Veterans Affairs (VA) tracked annually from 2014 to 2023, the percentage due to HCV alone fell from 36.1% to 8.7%, while cases linked to MASLD rose from 26.8% to 41.0%, Pedro Ochoa-Allemant, MD, MSCE, a clinical fellow in advanced/transplant hepatology at the University of Pennsylvania, et al, reported in the American Journal of Gastroenterology.

Cases due to alcohol use rose from 12.5% to 22.5%; those linked to metabolic dysfunction and alcohol use combined increased from 8.1% to 16.6%.

“This shift represents a major public health challenge,” Ochoa-Allemant told Federal Practitioner, noting that metabolic- and alcohol-related forms of cirrhosis require long-term care, unlike HCV, which has a cure.

“For this reason, we should move towards better strategies for early identification, risk stratification, and prevention, particularly in primary care where most patients are seen,” he said.

New Nomenclature, Rising Cases

Ochoa-Allemant et al launched the study to better understand the etiology of cirrhosis in light of the lack of new population-based research using recently revised steatotic liver disease nomenclature. In 2023, liver specialists removed “nonalcoholic fatty liver disease” and “nonalcoholic steatohepatitis” from the taxonomy, dismissing them as “exclusionary, negative” terms that “used potentially stigmatizing language.”

The study analyzed the Veterans Outcomes and Costs Associated with Liver Disease cohort, which includes > 1300 Veterans Health Administration (VHA) facilities.

In 2014, 0.84% of 5.7 million veterans who were actively treated at the VHA had cirrhosis. The prevalence grew to 1.29% of 6.0 million veterans in 2023, reflecting a direct increase in overall cases.

Hepatitis C Declines, Obesity Rises

Ochoa-Allemant attributed the changing picture of cirrhosis to available antiviral cures for HCV and the rising burden of obesity and diabetes in the general population.

“This shift means that prevention of cirrhosis is no longer primarily about treating HCV infection, but it now requires our focus on managing cardiometabolic risk factors and increased alcohol use,” he said.

He also noted that the study reported information on new cases of cirrhosis vs deaths that suggests MASLD rates are stabilizing while cases related to alcohol continue to rise.

A March 2026 study in The Lancet Gastroenterology & Hepatology reported similar trends. The analysis of 41,100 US adults with cirrhosis from 1988 to 2023 identified a significant increase in the prevalence of MASLD among those with steatotic liver disease (12.69% to 28.16%)

Alcohol-Related Cases May Be Undercounted

Elliot B. Tapper, MD, research professor of hepatology and associate professor of internal medicine at the University of Michigan Medical School, told Federal Practitioner that the findings are “striking, but not entirely unexpected given the obesity and diabetes epidemics.”

Tapper is familiar with the study but did not participate in it, added that the impact of alcohol may be even larger due to misclassification. The figures regarding alcohol-related cases “should probably be interpreted as a floor rather than a ceiling,” he said in an interview.

Moving forward, Tapper said “multidisciplinary collaboration with endocrinology, addiction medicine, and primary care is no longer optional. I would go further. Hepatologists cannot defer management to others.”

New Therapies for Metabolic-Related Liver Disease

Heather M. Patton, MD, chief of the Gastrointestinal Section at VA San Diego Healthcare System and clinical professor of medicine at the University of California at San Diego, told Federal Practitioner that “it is essential to ensure that patients with chronic HCV infection and advanced fibrosis continue to receive appropriate care following HCV cure, inclusive of liver cancer screening."

As for cases related to metabolic syndrome, Patton – who also is familiar with the study findings but did not take part – highlighted the role of newly approved therapies for metabolic-associated steatohepatitis. Most recently, the US Food and Drug Administration approved the GLP-1 agonist semaglutide for the condition.

The treatments represent “a tremendous opportunity to decrease incident cirrhosis,” Patton said in an interview. She also noted that primary care physicians and endocrinologists should recognize that “metabolic health is a major risk factor for liver disease, and utilizing liver health screening tools such as the FIB-4 score has the opportunity to save lives."

The authors of the new study cited limitations regarding generalizability such as male predominance and higher psychosocial comorbidity. They also noted that the decline in HCV-related cirrhosis probably occurred earlier in the VA system than elsewhere due to “greater identification and access to antiviral therapy.”

They also noted that attribution of cases to alcohol may be underestimated due to self-reporting.

No study funding is reported. Ochoa-Allemant discloses a relationship with the National Institutes of Health. Other authors disclose relationships with the National Institutes of Health, Grifols, National Institute on Aging, and the VA. Tapper discloses relationships with Madrigal, Resolution, Korro, Tortugas, Satellite, Bausch, Iota, and Mirum. Patton has no disclosures.

SAN FRANCISCO – The treatment of early-stage diffuse large B-cell lymphoma (DLBCL) is evolving after decades of failed attempts to improve on the standard treatment of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), a hematologist-oncologist said at the Association of Veterans Affairs (VA) Hematology/Oncology regional meeting on lymphoma on March 21.

A combination therapy known as pola-R-CHP is now the preferred option for many patients but has limited additional benefit, said Solomon A. Graf, MD, of the University of Washington and VA Puget Sound Health Care System. Pola-R-CHP is a modified regimen of R-CHOP that replaced vincristine in R-CHOP with polatuzumab vedotin.

The keys to treatment, Graf said, include consideration of disease variations that can affect therapy efficacy and understanding the special needs of older patients.

Understanding DLBCL

DLBCL is the most common non-Hodgkin lymphoma in the US with about 30,000 new cases per year; the median age at diagnosis is 67 years, Graf said.

“The overall incidence of DLBCL has been relatively stable over the last decades,” he said. “But gratifyingly, the rate of death from this disease has steadily been declining since about the turn of the century.”

Pola-R-CHP: A New Standard, Significant Limitations

From 2002-2022, “many attempts to improve on first-line DLBCL therapy did not pan out,” Graf said, as more than a dozen large phase 3 trials failed to dethrone R-CHOP as the standard. Most of the trials attempted to add an agent to R-CHOP but showed no additional benefit.

Then, in 2021, the landmark POLARIX study was published. The double-blind, randomized trial on the new regime showed a progression-free survival benefit (PFS) vs R-CHOP (76.7% vs 70.2% at 2 years, respectively). Safety profiles were similar between the 2 combination therapies.

However, overall survival (OS) did not differ.

"Pola-R-CHP is now considered a preferred standard, despite no overall survival benefit and despite increased upfront cost,” Graf said. (A 2023 analysis found that pola-R-CHP is more cost-effective than R-CHOP in DLBCL.)

Pola-R-CHP or Not Pola-R-CHP?

Pola-R-CHP is not for all patients with DLBCL. In advanced cases, Graf said, genomic analyses provide important information that helps clinicians understand whether patients will fare better with R-CHOP. Cell-of-origin classifications include germinal center B-cell like (GCB), activated B-cell like (ABC), and unclassifiable.

“If it’s GCB type, there's no clear benefit for Pola-R-CHP,” Graf said. “On the other hand, the ABC subtype does much better when treated with Pola-R-CHP.”

Graf highlighted the recently updated VA Oncology Clinical Pathway for DLBCL, which recommends cell-of-origin testing by the Hans algorithm for certain advanced-stage patients. The guidelines suggest R-CHOP for GCB-type patients and Pola-R-CHP for non–GCB-type patients. However, he cautioned that the Hans algorithm comes with an increased risk of misclassification.

Early-Stage Disease: Radiation or No Radiation?

About 25% to 30% of patients have stage I or II disease, and the landmark 1998 SWOG trial initially suggested that 3 cycles of CHOP plus radiation had superior PFS and OS compared with 8 cycles of CHOP alone, Graf said. This trial was conducted prior to the R-CHOP era. However, follow-up revealed that the benefit vanished over time and the risk of secondary cancers grew. “Both strategies are perfectly viable, but there isn’t as much of a preference anymore,” Graf said.

A pair of recent trials – a 2019 European study and a 2020 US study – support eliminating radiation and lowering the number of cycles of therapy in certain patients, he said.

Managing Older Patients

Patients with DLBCL tend to be older, Graf said, and many have comorbidities and other limitations. A standard course of 6 cycles of therapy may be too much for them, he said. Graf highlighted the Elderly Prognostic Index, a tool created by an Italian group that allows clinicians to predict outcomes based on patient fitness levels.

Graf offered additional guidance for this population:

• Consider corticosteroids in the prephase setting, which can be “very valuable” and improve a patient’s ECOG performance status, “giving you better confidence about proceeding with more standard therapy.”
• Include anthracycline-based therapies such as R-CHOP if appropriate, such as in patients who are focused on living longer, since they “are really crucial to achieving cure in patients with DLBCL.” Graf noted that he has “a low threshold to involve cardiology if there’s anthracycline use and some underlying cardiac comorbidity.”
• Adjust dosage as appropriate: “You can adjust in the middle, be rather flexible and creative about these doses and dosing levels as you get going with your patient and see just what they can tolerate,” he said. “Sometimes you can ramp it up over the course, and sometimes you have to ramp it down to respond to toxicities.”
• Be aware that older patients are at much higher risk of suffering from toxicities due to the vincristine component of R-CHOP. These include neurotoxicities and constipation.

Graf highlighted the phase 3 Polar Bear study, which may offer more insight into therapy options in patients aged ≥ 75 years who are frail or those aged ≥ 80 years. The trial is scheduled to end in early 2027.

Graf discloses relationships with Janssen, TG Therapeutics, BeOne, AstraZeneca, Genentech, Incyte, Eli Lilly, and Pfizer.

SAN FRANCISCO – The treatment of early-stage diffuse large B-cell lymphoma (DLBCL) is evolving after decades of failed attempts to improve on the standard treatment of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), a hematologist-oncologist said at the Association of Veterans Affairs (VA) Hematology/Oncology regional meeting on lymphoma on March 21.

A combination therapy known as pola-R-CHP is now the preferred option for many patients but has limited additional benefit, said Solomon A. Graf, MD, of the University of Washington and VA Puget Sound Health Care System. Pola-R-CHP is a modified regimen of R-CHOP that replaced vincristine in R-CHOP with polatuzumab vedotin.

The keys to treatment, Graf said, include consideration of disease variations that can affect therapy efficacy and understanding the special needs of older patients.

Understanding DLBCL

DLBCL is the most common non-Hodgkin lymphoma in the US with about 30,000 new cases per year; the median age at diagnosis is 67 years, Graf said.

“The overall incidence of DLBCL has been relatively stable over the last decades,” he said. “But gratifyingly, the rate of death from this disease has steadily been declining since about the turn of the century.”

Pola-R-CHP: A New Standard, Significant Limitations

From 2002-2022, “many attempts to improve on first-line DLBCL therapy did not pan out,” Graf said, as more than a dozen large phase 3 trials failed to dethrone R-CHOP as the standard. Most of the trials attempted to add an agent to R-CHOP but showed no additional benefit.

Then, in 2021, the landmark POLARIX study was published. The double-blind, randomized trial on the new regime showed a progression-free survival benefit (PFS) vs R-CHOP (76.7% vs 70.2% at 2 years, respectively). Safety profiles were similar between the 2 combination therapies.

However, overall survival (OS) did not differ.

"Pola-R-CHP is now considered a preferred standard, despite no overall survival benefit and despite increased upfront cost,” Graf said. (A 2023 analysis found that pola-R-CHP is more cost-effective than R-CHOP in DLBCL.)

Pola-R-CHP or Not Pola-R-CHP?

Pola-R-CHP is not for all patients with DLBCL. In advanced cases, Graf said, genomic analyses provide important information that helps clinicians understand whether patients will fare better with R-CHOP. Cell-of-origin classifications include germinal center B-cell like (GCB), activated B-cell like (ABC), and unclassifiable.

“If it’s GCB type, there's no clear benefit for Pola-R-CHP,” Graf said. “On the other hand, the ABC subtype does much better when treated with Pola-R-CHP.”

Graf highlighted the recently updated VA Oncology Clinical Pathway for DLBCL, which recommends cell-of-origin testing by the Hans algorithm for certain advanced-stage patients. The guidelines suggest R-CHOP for GCB-type patients and Pola-R-CHP for non–GCB-type patients. However, he cautioned that the Hans algorithm comes with an increased risk of misclassification.

Early-Stage Disease: Radiation or No Radiation?

About 25% to 30% of patients have stage I or II disease, and the landmark 1998 SWOG trial initially suggested that 3 cycles of CHOP plus radiation had superior PFS and OS compared with 8 cycles of CHOP alone, Graf said. This trial was conducted prior to the R-CHOP era. However, follow-up revealed that the benefit vanished over time and the risk of secondary cancers grew. “Both strategies are perfectly viable, but there isn’t as much of a preference anymore,” Graf said.

A pair of recent trials – a 2019 European study and a 2020 US study – support eliminating radiation and lowering the number of cycles of therapy in certain patients, he said.

Managing Older Patients

Patients with DLBCL tend to be older, Graf said, and many have comorbidities and other limitations. A standard course of 6 cycles of therapy may be too much for them, he said. Graf highlighted the Elderly Prognostic Index, a tool created by an Italian group that allows clinicians to predict outcomes based on patient fitness levels.

Graf offered additional guidance for this population:

• Consider corticosteroids in the prephase setting, which can be “very valuable” and improve a patient’s ECOG performance status, “giving you better confidence about proceeding with more standard therapy.”
• Include anthracycline-based therapies such as R-CHOP if appropriate, such as in patients who are focused on living longer, since they “are really crucial to achieving cure in patients with DLBCL.” Graf noted that he has “a low threshold to involve cardiology if there’s anthracycline use and some underlying cardiac comorbidity.”
• Adjust dosage as appropriate: “You can adjust in the middle, be rather flexible and creative about these doses and dosing levels as you get going with your patient and see just what they can tolerate,” he said. “Sometimes you can ramp it up over the course, and sometimes you have to ramp it down to respond to toxicities.”
• Be aware that older patients are at much higher risk of suffering from toxicities due to the vincristine component of R-CHOP. These include neurotoxicities and constipation.

Graf highlighted the phase 3 Polar Bear study, which may offer more insight into therapy options in patients aged ≥ 75 years who are frail or those aged ≥ 80 years. The trial is scheduled to end in early 2027.

Graf discloses relationships with Janssen, TG Therapeutics, BeOne, AstraZeneca, Genentech, Incyte, Eli Lilly, and Pfizer.

SAN FRANCISCO – The treatment of early-stage diffuse large B-cell lymphoma (DLBCL) is evolving after decades of failed attempts to improve on the standard treatment of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), a hematologist-oncologist said at the Association of Veterans Affairs (VA) Hematology/Oncology regional meeting on lymphoma on March 21.

A combination therapy known as pola-R-CHP is now the preferred option for many patients but has limited additional benefit, said Solomon A. Graf, MD, of the University of Washington and VA Puget Sound Health Care System. Pola-R-CHP is a modified regimen of R-CHOP that replaced vincristine in R-CHOP with polatuzumab vedotin.

The keys to treatment, Graf said, include consideration of disease variations that can affect therapy efficacy and understanding the special needs of older patients.

Understanding DLBCL

DLBCL is the most common non-Hodgkin lymphoma in the US with about 30,000 new cases per year; the median age at diagnosis is 67 years, Graf said.

“The overall incidence of DLBCL has been relatively stable over the last decades,” he said. “But gratifyingly, the rate of death from this disease has steadily been declining since about the turn of the century.”

Pola-R-CHP: A New Standard, Significant Limitations

From 2002-2022, “many attempts to improve on first-line DLBCL therapy did not pan out,” Graf said, as more than a dozen large phase 3 trials failed to dethrone R-CHOP as the standard. Most of the trials attempted to add an agent to R-CHOP but showed no additional benefit.

Then, in 2021, the landmark POLARIX study was published. The double-blind, randomized trial on the new regime showed a progression-free survival benefit (PFS) vs R-CHOP (76.7% vs 70.2% at 2 years, respectively). Safety profiles were similar between the 2 combination therapies.

However, overall survival (OS) did not differ.

"Pola-R-CHP is now considered a preferred standard, despite no overall survival benefit and despite increased upfront cost,” Graf said. (A 2023 analysis found that pola-R-CHP is more cost-effective than R-CHOP in DLBCL.)

Pola-R-CHP or Not Pola-R-CHP?

Pola-R-CHP is not for all patients with DLBCL. In advanced cases, Graf said, genomic analyses provide important information that helps clinicians understand whether patients will fare better with R-CHOP. Cell-of-origin classifications include germinal center B-cell like (GCB), activated B-cell like (ABC), and unclassifiable.

“If it’s GCB type, there's no clear benefit for Pola-R-CHP,” Graf said. “On the other hand, the ABC subtype does much better when treated with Pola-R-CHP.”

Graf highlighted the recently updated VA Oncology Clinical Pathway for DLBCL, which recommends cell-of-origin testing by the Hans algorithm for certain advanced-stage patients. The guidelines suggest R-CHOP for GCB-type patients and Pola-R-CHP for non–GCB-type patients. However, he cautioned that the Hans algorithm comes with an increased risk of misclassification.

Early-Stage Disease: Radiation or No Radiation?

About 25% to 30% of patients have stage I or II disease, and the landmark 1998 SWOG trial initially suggested that 3 cycles of CHOP plus radiation had superior PFS and OS compared with 8 cycles of CHOP alone, Graf said. This trial was conducted prior to the R-CHOP era. However, follow-up revealed that the benefit vanished over time and the risk of secondary cancers grew. “Both strategies are perfectly viable, but there isn’t as much of a preference anymore,” Graf said.

A pair of recent trials – a 2019 European study and a 2020 US study – support eliminating radiation and lowering the number of cycles of therapy in certain patients, he said.

Managing Older Patients

Patients with DLBCL tend to be older, Graf said, and many have comorbidities and other limitations. A standard course of 6 cycles of therapy may be too much for them, he said. Graf highlighted the Elderly Prognostic Index, a tool created by an Italian group that allows clinicians to predict outcomes based on patient fitness levels.

Graf offered additional guidance for this population:

• Consider corticosteroids in the prephase setting, which can be “very valuable” and improve a patient’s ECOG performance status, “giving you better confidence about proceeding with more standard therapy.”
• Include anthracycline-based therapies such as R-CHOP if appropriate, such as in patients who are focused on living longer, since they “are really crucial to achieving cure in patients with DLBCL.” Graf noted that he has “a low threshold to involve cardiology if there’s anthracycline use and some underlying cardiac comorbidity.”
• Adjust dosage as appropriate: “You can adjust in the middle, be rather flexible and creative about these doses and dosing levels as you get going with your patient and see just what they can tolerate,” he said. “Sometimes you can ramp it up over the course, and sometimes you have to ramp it down to respond to toxicities.”
• Be aware that older patients are at much higher risk of suffering from toxicities due to the vincristine component of R-CHOP. These include neurotoxicities and constipation.

Graf highlighted the phase 3 Polar Bear study, which may offer more insight into therapy options in patients aged ≥ 75 years who are frail or those aged ≥ 80 years. The trial is scheduled to end in early 2027.

Graf discloses relationships with Janssen, TG Therapeutics, BeOne, AstraZeneca, Genentech, Incyte, Eli Lilly, and Pfizer.

TOPLINE:

Among 1.3 million male veterans treated for prostate cancer, 11,327 (0.86%) developed breast cancer an average of 5.4 years after initial diagnosis. Younger age at prostate cancer diagnosis, metastatic disease, androgen deprivation therapy (ADT), radiation treatment, and prolonged use of certain cardiovascular disease (CVD) medications were associated with increased risk for breast cancer.

METHODOLOGY:

• Researchers used a retrospective cohort design in Veterans Health Administration (VHA) care, pulling data from the Veterans Affairs (VA) Prostate Cancer Data Core at the VA Corporate Data Warehouse.
• Participants included 1,314,492 male veterans with prostate cancer treated at VHA facilities from January 1, 2000, to March 12, 2024.
• Exposure definitions included prostate cancer treatments (ADT, anti-androgen treatment, radiation-brachytherapy, and platinum chemotherapy) and CVD medications (furosemide, spironolactone, digoxin) captured via inpatient/outpatient/fee-based pharmacy and Current Procedural Terminology codes.
• Analysis measured time from prostate cancer diagnosis to breast cancer diagnosis, death, or March 12, 2024, applying Cox proportional hazards and Fine-Gray competing risk methods, with a sensitivity analysis adding body mass index (BMI) after excluding 71,718 missing values.

TAKEAWAY:

• Metastatic prostate cancer at diagnosis more than doubled the risk for breast cancer compared to nonmetastatic disease (hazard ratio [HR], 2.03; 95% CI, 1.90-2.17; P < .0001; subdistribution hazard ratio [SHR], 1.68; 95% CI, 1.57-1.81; P < .0001).
• Younger age at prostate cancer diagnosis was associated with increased risk for breast cancer (HR, 0.97; 95% CI, 0.97-0.98; P < .0001; SHR, 0.957; 95% CI, 0.955-0.959; P < .0001), indicating that for each additional year of age at diagnosis, the risk decreased.
• Continuation of CVD medications after prostate cancer diagnosis was associated with increased risk for breast cancer: furosemide (HR, 1.51; 95% CI, 1.39-1.63; P < .0001; SHR, 1.21; 95% CI, 1.12-1.31; P < .0001), spironolactone (HR, 1.36; 95% CI, 1.15-1.61; P = .0004; SHR, 1.23; 95% CI, 1.04-1.47; P = .0174), and digoxin (HR, 1.49; 95% CI, 1.29-1.72; P < .0001; SHR, 1.26; 95% CI, 1.10-1.46; P = .0015).
• Radiation therapy and ADT were associated with increased risk for breast cancer (radiation: HR, 1.06; 95% CI, 1.02-1.11; P = .0088; SHR, 1.10; 95% CI, 1.05-1.15; P < .0001; ADT: HR, 1.24; 95% CI, 1.17-1.32; P < .0001; SHR, 1.28; 95% CI, 1.20-1.37; P < .0001), while abiraterone was associated with decreased risk (HR, 0.36; 95% CI, 0.31-0.42; P < .0001; SHR, 0.39; 95% CI, 0.34-0.45; P < .0001).

IN PRACTICE:

"While there is a lack of data, male veterans with previous prostate cancer are at an elevated risk of breast cancer (0.87%), than their civilian counterparts (0.14%),” the authors wrote. “To address the current gap in knowledge and data, this study leveraged an existing large cohort of male veterans with prostate cancer and examined factors associated with increased risk of male breast cancer."

SOURCE:

The study was led by Erum Z. Whyne, VA North Texas Health Care System in Dallas, and Haekyung Jeon-Slaughter, University of Texas Southwestern Medical Center in Dallas. It was published online in The Prostate.

LIMITATIONS:

Though the study findings are based on large, representative data from male veterans with previously diagnosed prostate cancer, the results might not be generalizable to the overall male breast cancer population. As a retrospective cohort study, results may be biased and causality is difficult to establish. The study did not examine other known risk factors for male breast cancer incidence, such as family history, BRCA2 mutations, and military environmental exposure due to lack of data. BMI had missingness of 5.46% (n = 71,718) and was not included as a covariate in the final model, though sensitivity analysis showed it was not significantly associated with increased risk for male breast cancer.

DISCLOSURES:

The research was supported using resources and facilities of the VA Informatics and Computing Infrastructure (VINCI), VA HSR RES 13-457. The VA North Texas Health Care System Institutional Review Board approved the study and waived informed consent. No conflicts of interest were disclosed by the authors.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

TOPLINE:

Among 1.3 million male veterans treated for prostate cancer, 11,327 (0.86%) developed breast cancer an average of 5.4 years after initial diagnosis. Younger age at prostate cancer diagnosis, metastatic disease, androgen deprivation therapy (ADT), radiation treatment, and prolonged use of certain cardiovascular disease (CVD) medications were associated with increased risk for breast cancer.

METHODOLOGY:

• Researchers used a retrospective cohort design in Veterans Health Administration (VHA) care, pulling data from the Veterans Affairs (VA) Prostate Cancer Data Core at the VA Corporate Data Warehouse.
• Participants included 1,314,492 male veterans with prostate cancer treated at VHA facilities from January 1, 2000, to March 12, 2024.
• Exposure definitions included prostate cancer treatments (ADT, anti-androgen treatment, radiation-brachytherapy, and platinum chemotherapy) and CVD medications (furosemide, spironolactone, digoxin) captured via inpatient/outpatient/fee-based pharmacy and Current Procedural Terminology codes.
• Analysis measured time from prostate cancer diagnosis to breast cancer diagnosis, death, or March 12, 2024, applying Cox proportional hazards and Fine-Gray competing risk methods, with a sensitivity analysis adding body mass index (BMI) after excluding 71,718 missing values.

TAKEAWAY:

• Metastatic prostate cancer at diagnosis more than doubled the risk for breast cancer compared to nonmetastatic disease (hazard ratio [HR], 2.03; 95% CI, 1.90-2.17; P < .0001; subdistribution hazard ratio [SHR], 1.68; 95% CI, 1.57-1.81; P < .0001).
• Younger age at prostate cancer diagnosis was associated with increased risk for breast cancer (HR, 0.97; 95% CI, 0.97-0.98; P < .0001; SHR, 0.957; 95% CI, 0.955-0.959; P < .0001), indicating that for each additional year of age at diagnosis, the risk decreased.
• Continuation of CVD medications after prostate cancer diagnosis was associated with increased risk for breast cancer: furosemide (HR, 1.51; 95% CI, 1.39-1.63; P < .0001; SHR, 1.21; 95% CI, 1.12-1.31; P < .0001), spironolactone (HR, 1.36; 95% CI, 1.15-1.61; P = .0004; SHR, 1.23; 95% CI, 1.04-1.47; P = .0174), and digoxin (HR, 1.49; 95% CI, 1.29-1.72; P < .0001; SHR, 1.26; 95% CI, 1.10-1.46; P = .0015).
• Radiation therapy and ADT were associated with increased risk for breast cancer (radiation: HR, 1.06; 95% CI, 1.02-1.11; P = .0088; SHR, 1.10; 95% CI, 1.05-1.15; P < .0001; ADT: HR, 1.24; 95% CI, 1.17-1.32; P < .0001; SHR, 1.28; 95% CI, 1.20-1.37; P < .0001), while abiraterone was associated with decreased risk (HR, 0.36; 95% CI, 0.31-0.42; P < .0001; SHR, 0.39; 95% CI, 0.34-0.45; P < .0001).

IN PRACTICE:

"While there is a lack of data, male veterans with previous prostate cancer are at an elevated risk of breast cancer (0.87%), than their civilian counterparts (0.14%),” the authors wrote. “To address the current gap in knowledge and data, this study leveraged an existing large cohort of male veterans with prostate cancer and examined factors associated with increased risk of male breast cancer."

SOURCE:

The study was led by Erum Z. Whyne, VA North Texas Health Care System in Dallas, and Haekyung Jeon-Slaughter, University of Texas Southwestern Medical Center in Dallas. It was published online in The Prostate.

LIMITATIONS:

Though the study findings are based on large, representative data from male veterans with previously diagnosed prostate cancer, the results might not be generalizable to the overall male breast cancer population. As a retrospective cohort study, results may be biased and causality is difficult to establish. The study did not examine other known risk factors for male breast cancer incidence, such as family history, BRCA2 mutations, and military environmental exposure due to lack of data. BMI had missingness of 5.46% (n = 71,718) and was not included as a covariate in the final model, though sensitivity analysis showed it was not significantly associated with increased risk for male breast cancer.

DISCLOSURES:

The research was supported using resources and facilities of the VA Informatics and Computing Infrastructure (VINCI), VA HSR RES 13-457. The VA North Texas Health Care System Institutional Review Board approved the study and waived informed consent. No conflicts of interest were disclosed by the authors.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

TOPLINE:

Among 1.3 million male veterans treated for prostate cancer, 11,327 (0.86%) developed breast cancer an average of 5.4 years after initial diagnosis. Younger age at prostate cancer diagnosis, metastatic disease, androgen deprivation therapy (ADT), radiation treatment, and prolonged use of certain cardiovascular disease (CVD) medications were associated with increased risk for breast cancer.

METHODOLOGY:

• Researchers used a retrospective cohort design in Veterans Health Administration (VHA) care, pulling data from the Veterans Affairs (VA) Prostate Cancer Data Core at the VA Corporate Data Warehouse.
• Participants included 1,314,492 male veterans with prostate cancer treated at VHA facilities from January 1, 2000, to March 12, 2024.
• Exposure definitions included prostate cancer treatments (ADT, anti-androgen treatment, radiation-brachytherapy, and platinum chemotherapy) and CVD medications (furosemide, spironolactone, digoxin) captured via inpatient/outpatient/fee-based pharmacy and Current Procedural Terminology codes.
• Analysis measured time from prostate cancer diagnosis to breast cancer diagnosis, death, or March 12, 2024, applying Cox proportional hazards and Fine-Gray competing risk methods, with a sensitivity analysis adding body mass index (BMI) after excluding 71,718 missing values.

TAKEAWAY:

• Metastatic prostate cancer at diagnosis more than doubled the risk for breast cancer compared to nonmetastatic disease (hazard ratio [HR], 2.03; 95% CI, 1.90-2.17; P < .0001; subdistribution hazard ratio [SHR], 1.68; 95% CI, 1.57-1.81; P < .0001).
• Younger age at prostate cancer diagnosis was associated with increased risk for breast cancer (HR, 0.97; 95% CI, 0.97-0.98; P < .0001; SHR, 0.957; 95% CI, 0.955-0.959; P < .0001), indicating that for each additional year of age at diagnosis, the risk decreased.
• Continuation of CVD medications after prostate cancer diagnosis was associated with increased risk for breast cancer: furosemide (HR, 1.51; 95% CI, 1.39-1.63; P < .0001; SHR, 1.21; 95% CI, 1.12-1.31; P < .0001), spironolactone (HR, 1.36; 95% CI, 1.15-1.61; P = .0004; SHR, 1.23; 95% CI, 1.04-1.47; P = .0174), and digoxin (HR, 1.49; 95% CI, 1.29-1.72; P < .0001; SHR, 1.26; 95% CI, 1.10-1.46; P = .0015).
• Radiation therapy and ADT were associated with increased risk for breast cancer (radiation: HR, 1.06; 95% CI, 1.02-1.11; P = .0088; SHR, 1.10; 95% CI, 1.05-1.15; P < .0001; ADT: HR, 1.24; 95% CI, 1.17-1.32; P < .0001; SHR, 1.28; 95% CI, 1.20-1.37; P < .0001), while abiraterone was associated with decreased risk (HR, 0.36; 95% CI, 0.31-0.42; P < .0001; SHR, 0.39; 95% CI, 0.34-0.45; P < .0001).

IN PRACTICE:

"While there is a lack of data, male veterans with previous prostate cancer are at an elevated risk of breast cancer (0.87%), than their civilian counterparts (0.14%),” the authors wrote. “To address the current gap in knowledge and data, this study leveraged an existing large cohort of male veterans with prostate cancer and examined factors associated with increased risk of male breast cancer."

SOURCE:

The study was led by Erum Z. Whyne, VA North Texas Health Care System in Dallas, and Haekyung Jeon-Slaughter, University of Texas Southwestern Medical Center in Dallas. It was published online in The Prostate.

LIMITATIONS:

Though the study findings are based on large, representative data from male veterans with previously diagnosed prostate cancer, the results might not be generalizable to the overall male breast cancer population. As a retrospective cohort study, results may be biased and causality is difficult to establish. The study did not examine other known risk factors for male breast cancer incidence, such as family history, BRCA2 mutations, and military environmental exposure due to lack of data. BMI had missingness of 5.46% (n = 71,718) and was not included as a covariate in the final model, though sensitivity analysis showed it was not significantly associated with increased risk for male breast cancer.

DISCLOSURES:

The research was supported using resources and facilities of the VA Informatics and Computing Infrastructure (VINCI), VA HSR RES 13-457. The VA North Texas Health Care System Institutional Review Board approved the study and waived informed consent. No conflicts of interest were disclosed by the authors.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

TOPLINE:

Among adults with obesity, nonsurgical weight loss was significantly associated with reduced odds for developing obesity-related and other cancers at 3 and 5 years, a study of real-world data found.

METHODOLOGY:

• Although weight loss after bariatric surgery is linked to a reduced risk for cancer, the effect of nonsurgical weight loss on cancer risk remains unclear.
• Researchers conducted a retrospective observational study using electronic health record data from a US health system to assess the association between nonsurgical weight loss and the risk for cancer among adults with obesity.
• The inclusion criteria were age of ≥ 20 years, BMI > 30, and at least seven health system visits over 3 years. Patients with a history of alcohol or substance abuse, amputations, HIV infection, organ transplant, thyroid problems, or those who underwent bariatric surgery were excluded.
• The 143,630 patients who met inclusion criteria (7703 cancer cases and 135,927 controls) were divided into 3 cohorts based on weight change over time intervals of 3 years (115,942 patients), 5 years (105,472 patients), and 10 years (59,112 patients).
• Primary endpoints included obesity-related cancers (esophageal cancer, liver cancer, gallbladder cancer, pancreatic cancer, colorectal cancer, renal cell carcinoma, endometrial cancer, multiple myeloma, and postmenopausal breast cancer), and secondary endpoints included all malignant neoplasms.

TAKEAWAY:

• Each 1% reduction in BMI was associated with reduced odds of obesity-related cancers at 3 years and 5 years (odds ratio [OR], 0.99 and 0.989, respectively; P < .001 for both). These results translate to 5% weight loss corresponding to 4.9% and 5.4% reductions in obesity-related cancer odds at 3 and 5 years, respectively.
• Weight loss was associated with reduced odds of endometrial cancer at 3, 5, and 10 years (OR, 0.978; P < .05), of renal cell carcinoma at 3 and 5 years (OR, 0.983; P < .05), and of multiple myeloma at 10 years (OR, 0.969; P = .004).
• Weight loss was also associated with reduced odds of developing any malignancy at 3 years (OR, 0.992), 5 years (OR, 0.994), and 10 years (OR, 0.991; P = .001 for all). These results translate into a 5% weight loss corresponding to 3.9%, 3%, and 4.4% lower odds of any malignancy at 3, 5, and 10 years, respectively.

IN PRACTICE:

"Real-world weight loss was associated with a decreased risk of developing obesity-related cancers and all other cancers. Our study serves as a call for action and a strong public health message to healthcare stakeholders to intensify efforts and resources to treat obesity as a chronic disease to help reduce the risk of developing cancer," the author wrote.

SOURCE:

This study, led by endocrinologist Kenda Alkwatli, MD, Starling Physicians, Wethersfield, Connecticut, was published online in Obesity.

LIMITATIONS:

The study included only individuals with sufficient longitudinal health records, which may have introduced selection bias. It could not distinguish between intentional and unintentional weight loss or differentiate between fat and lean mass. Due to its observational nature, the study could not assess whether weight loss preceding cancer diagnosis was related to delay in diagnosis.

DISCLOSURES:

The study was funded in part by the Cleveland Clinic Center for Quantitative Metabolic Research. Three authors reported receiving research funding, consulting fees, honoraria, grants, or research support and holding patent applications, license agreements, leadership roles, or equity in healthcare and biotechnology companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

Among adults with obesity, nonsurgical weight loss was significantly associated with reduced odds for developing obesity-related and other cancers at 3 and 5 years, a study of real-world data found.

METHODOLOGY:

• Although weight loss after bariatric surgery is linked to a reduced risk for cancer, the effect of nonsurgical weight loss on cancer risk remains unclear.
• Researchers conducted a retrospective observational study using electronic health record data from a US health system to assess the association between nonsurgical weight loss and the risk for cancer among adults with obesity.
• The inclusion criteria were age of ≥ 20 years, BMI > 30, and at least seven health system visits over 3 years. Patients with a history of alcohol or substance abuse, amputations, HIV infection, organ transplant, thyroid problems, or those who underwent bariatric surgery were excluded.
• The 143,630 patients who met inclusion criteria (7703 cancer cases and 135,927 controls) were divided into 3 cohorts based on weight change over time intervals of 3 years (115,942 patients), 5 years (105,472 patients), and 10 years (59,112 patients).
• Primary endpoints included obesity-related cancers (esophageal cancer, liver cancer, gallbladder cancer, pancreatic cancer, colorectal cancer, renal cell carcinoma, endometrial cancer, multiple myeloma, and postmenopausal breast cancer), and secondary endpoints included all malignant neoplasms.

TAKEAWAY:

• Each 1% reduction in BMI was associated with reduced odds of obesity-related cancers at 3 years and 5 years (odds ratio [OR], 0.99 and 0.989, respectively; P < .001 for both). These results translate to 5% weight loss corresponding to 4.9% and 5.4% reductions in obesity-related cancer odds at 3 and 5 years, respectively.
• Weight loss was associated with reduced odds of endometrial cancer at 3, 5, and 10 years (OR, 0.978; P < .05), of renal cell carcinoma at 3 and 5 years (OR, 0.983; P < .05), and of multiple myeloma at 10 years (OR, 0.969; P = .004).
• Weight loss was also associated with reduced odds of developing any malignancy at 3 years (OR, 0.992), 5 years (OR, 0.994), and 10 years (OR, 0.991; P = .001 for all). These results translate into a 5% weight loss corresponding to 3.9%, 3%, and 4.4% lower odds of any malignancy at 3, 5, and 10 years, respectively.

IN PRACTICE:

"Real-world weight loss was associated with a decreased risk of developing obesity-related cancers and all other cancers. Our study serves as a call for action and a strong public health message to healthcare stakeholders to intensify efforts and resources to treat obesity as a chronic disease to help reduce the risk of developing cancer," the author wrote.

SOURCE:

This study, led by endocrinologist Kenda Alkwatli, MD, Starling Physicians, Wethersfield, Connecticut, was published online in Obesity.

LIMITATIONS:

The study included only individuals with sufficient longitudinal health records, which may have introduced selection bias. It could not distinguish between intentional and unintentional weight loss or differentiate between fat and lean mass. Due to its observational nature, the study could not assess whether weight loss preceding cancer diagnosis was related to delay in diagnosis.

DISCLOSURES:

The study was funded in part by the Cleveland Clinic Center for Quantitative Metabolic Research. Three authors reported receiving research funding, consulting fees, honoraria, grants, or research support and holding patent applications, license agreements, leadership roles, or equity in healthcare and biotechnology companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

Among adults with obesity, nonsurgical weight loss was significantly associated with reduced odds for developing obesity-related and other cancers at 3 and 5 years, a study of real-world data found.

METHODOLOGY:

• Although weight loss after bariatric surgery is linked to a reduced risk for cancer, the effect of nonsurgical weight loss on cancer risk remains unclear.
• Researchers conducted a retrospective observational study using electronic health record data from a US health system to assess the association between nonsurgical weight loss and the risk for cancer among adults with obesity.
• The inclusion criteria were age of ≥ 20 years, BMI > 30, and at least seven health system visits over 3 years. Patients with a history of alcohol or substance abuse, amputations, HIV infection, organ transplant, thyroid problems, or those who underwent bariatric surgery were excluded.
• The 143,630 patients who met inclusion criteria (7703 cancer cases and 135,927 controls) were divided into 3 cohorts based on weight change over time intervals of 3 years (115,942 patients), 5 years (105,472 patients), and 10 years (59,112 patients).
• Primary endpoints included obesity-related cancers (esophageal cancer, liver cancer, gallbladder cancer, pancreatic cancer, colorectal cancer, renal cell carcinoma, endometrial cancer, multiple myeloma, and postmenopausal breast cancer), and secondary endpoints included all malignant neoplasms.

TAKEAWAY:

• Each 1% reduction in BMI was associated with reduced odds of obesity-related cancers at 3 years and 5 years (odds ratio [OR], 0.99 and 0.989, respectively; P < .001 for both). These results translate to 5% weight loss corresponding to 4.9% and 5.4% reductions in obesity-related cancer odds at 3 and 5 years, respectively.
• Weight loss was associated with reduced odds of endometrial cancer at 3, 5, and 10 years (OR, 0.978; P < .05), of renal cell carcinoma at 3 and 5 years (OR, 0.983; P < .05), and of multiple myeloma at 10 years (OR, 0.969; P = .004).
• Weight loss was also associated with reduced odds of developing any malignancy at 3 years (OR, 0.992), 5 years (OR, 0.994), and 10 years (OR, 0.991; P = .001 for all). These results translate into a 5% weight loss corresponding to 3.9%, 3%, and 4.4% lower odds of any malignancy at 3, 5, and 10 years, respectively.

IN PRACTICE:

"Real-world weight loss was associated with a decreased risk of developing obesity-related cancers and all other cancers. Our study serves as a call for action and a strong public health message to healthcare stakeholders to intensify efforts and resources to treat obesity as a chronic disease to help reduce the risk of developing cancer," the author wrote.

SOURCE:

This study, led by endocrinologist Kenda Alkwatli, MD, Starling Physicians, Wethersfield, Connecticut, was published online in Obesity.

LIMITATIONS:

The study included only individuals with sufficient longitudinal health records, which may have introduced selection bias. It could not distinguish between intentional and unintentional weight loss or differentiate between fat and lean mass. Due to its observational nature, the study could not assess whether weight loss preceding cancer diagnosis was related to delay in diagnosis.

DISCLOSURES:

The study was funded in part by the Cleveland Clinic Center for Quantitative Metabolic Research. Three authors reported receiving research funding, consulting fees, honoraria, grants, or research support and holding patent applications, license agreements, leadership roles, or equity in healthcare and biotechnology companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

Two studies published in March by researchers at the Veterans Affairs Saint Louis Healthcare System highlight the clinical significance of glucagon-like peptide 1 receptor agonists (GLP-1s) and their impact on reducing substance use disorder (SUD) risks. The studies also explore the impact of GLP-1 discontinuation or interruption on their effectiveness in protection against the cardiovascular events.

In one study, Al-Aly et al assigned 606,434 veterans with type 2 diabetes to 1 of 2 protocols, comparing GLP-1s with sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and followed the patients for up to 3 years. Al-Aly et al found that GLP-1s were “consistently associated” with a lower risk of developing SUDs, including those involving alcohol, cannabis, cocaine, nicotine, and opioids. The findings suggested “potential preventive effects across a broad range of addictive substances.”

In participants with pre-existing SUDs, GLP-1s were also associated with reduced risks of SUD-related emergency department visits, hospital admissions, and mortality, in addition to drug overdoses and suicidal behaviors. A study published in 2025 from the same research group reported that GLP-1s could have a variety of health benefits, including reducing the risk of incident alcohol and cannabis disorders, neurocognitive disorders (such as Alzheimer's disease and dementia), coagulation disorders, cardiometabolic disorders, infectious illnesses and several respiratory conditions, but less was known about the potential for preventing development of opioid use disorder and other SUDs. 

GLP-1s target the brain’s reward pathways and have recently made attention-grabbing headlines regarding celebrity weight loss, with social media boosting public interest. One study, for example, found 100 videos on TikTok with the #Ozempic viewed nearly 70 million times.

Al-Aly et al used SGLT-2 inhibitors as active comparators because “they have no established direct actions on mesolimbic reward circuits in the brain, whereas GLP-1 receptors are present in areas of the brain involved in impulse control and reward signaling.”

The second study found that quitting or pausing GLP-1 treatment for 6 months could have a rebound effect and possibly reverse any progress. Discontinuing GLP-1 treatment is common, with rates ranging from 36% to 81% in the first year. Stopping or interrupting the treatment is often followed by weight regain and a rebound in inflammation, both major drivers in cardiovascular disease risk. 

The study followed 132,551 VA patients using GLP-1s and 201,136 using sulfonylureas from 2017 through 2023. About two-thirds of participants took semaglutide, prescribed as Ozempic to treat diabetes and Wegovy to reduce obesity. A total of 26% of the participants stopped GLP-1 treatment during the follow-up period, with 64% occurring during the first year. Most (67%) treatment interruptions also came in the first year.

Compared with incident use of sulfonylureas, incident use of GLP-1s was associated with a reduced risk of heart attack, stroke, or death. Patients who took the GLP-1s without interruption > 3 years experienced an 18% lower risk for heart attack or stroke.  

Cardiovascular benefits accumulated with continuous use over 3 years, but even brief periods of discontinuations or interruptions could progressively erode and ultimately reverse this protection, the researchers found. Discontinuing treatment for half a year was associated with an increased risk of major adverse cardiovascular events (incidence risk ratio [IRR], 1.04), while longer gaps were progressively associated with a higher risk of disease (IRR, 1.12 for 1 year; IRR, 1.16 for 2 years of interrupted use, respectively).

Dr. Ziyad Al-Aly, a study author and Chief of the Research and Education Service at the Veterans Affairs Saint Louis Healthcare System, called it “metabolic whiplash.” In an interview, he said it was important to caution patients that these medications “need to be taken for the long haul. This is not something (patients) can take for a month or 2 or 3 and get off of it. It's not going to work like that.”

Two studies published in March by researchers at the Veterans Affairs Saint Louis Healthcare System highlight the clinical significance of glucagon-like peptide 1 receptor agonists (GLP-1s) and their impact on reducing substance use disorder (SUD) risks. The studies also explore the impact of GLP-1 discontinuation or interruption on their effectiveness in protection against the cardiovascular events.

In one study, Al-Aly et al assigned 606,434 veterans with type 2 diabetes to 1 of 2 protocols, comparing GLP-1s with sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and followed the patients for up to 3 years. Al-Aly et al found that GLP-1s were “consistently associated” with a lower risk of developing SUDs, including those involving alcohol, cannabis, cocaine, nicotine, and opioids. The findings suggested “potential preventive effects across a broad range of addictive substances.”

In participants with pre-existing SUDs, GLP-1s were also associated with reduced risks of SUD-related emergency department visits, hospital admissions, and mortality, in addition to drug overdoses and suicidal behaviors. A study published in 2025 from the same research group reported that GLP-1s could have a variety of health benefits, including reducing the risk of incident alcohol and cannabis disorders, neurocognitive disorders (such as Alzheimer's disease and dementia), coagulation disorders, cardiometabolic disorders, infectious illnesses and several respiratory conditions, but less was known about the potential for preventing development of opioid use disorder and other SUDs. 

GLP-1s target the brain’s reward pathways and have recently made attention-grabbing headlines regarding celebrity weight loss, with social media boosting public interest. One study, for example, found 100 videos on TikTok with the #Ozempic viewed nearly 70 million times.

Al-Aly et al used SGLT-2 inhibitors as active comparators because “they have no established direct actions on mesolimbic reward circuits in the brain, whereas GLP-1 receptors are present in areas of the brain involved in impulse control and reward signaling.”

The second study found that quitting or pausing GLP-1 treatment for 6 months could have a rebound effect and possibly reverse any progress. Discontinuing GLP-1 treatment is common, with rates ranging from 36% to 81% in the first year. Stopping or interrupting the treatment is often followed by weight regain and a rebound in inflammation, both major drivers in cardiovascular disease risk. 

The study followed 132,551 VA patients using GLP-1s and 201,136 using sulfonylureas from 2017 through 2023. About two-thirds of participants took semaglutide, prescribed as Ozempic to treat diabetes and Wegovy to reduce obesity. A total of 26% of the participants stopped GLP-1 treatment during the follow-up period, with 64% occurring during the first year. Most (67%) treatment interruptions also came in the first year.

Compared with incident use of sulfonylureas, incident use of GLP-1s was associated with a reduced risk of heart attack, stroke, or death. Patients who took the GLP-1s without interruption > 3 years experienced an 18% lower risk for heart attack or stroke.  

Cardiovascular benefits accumulated with continuous use over 3 years, but even brief periods of discontinuations or interruptions could progressively erode and ultimately reverse this protection, the researchers found. Discontinuing treatment for half a year was associated with an increased risk of major adverse cardiovascular events (incidence risk ratio [IRR], 1.04), while longer gaps were progressively associated with a higher risk of disease (IRR, 1.12 for 1 year; IRR, 1.16 for 2 years of interrupted use, respectively).

Dr. Ziyad Al-Aly, a study author and Chief of the Research and Education Service at the Veterans Affairs Saint Louis Healthcare System, called it “metabolic whiplash.” In an interview, he said it was important to caution patients that these medications “need to be taken for the long haul. This is not something (patients) can take for a month or 2 or 3 and get off of it. It's not going to work like that.”

Two studies published in March by researchers at the Veterans Affairs Saint Louis Healthcare System highlight the clinical significance of glucagon-like peptide 1 receptor agonists (GLP-1s) and their impact on reducing substance use disorder (SUD) risks. The studies also explore the impact of GLP-1 discontinuation or interruption on their effectiveness in protection against the cardiovascular events.

In one study, Al-Aly et al assigned 606,434 veterans with type 2 diabetes to 1 of 2 protocols, comparing GLP-1s with sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and followed the patients for up to 3 years. Al-Aly et al found that GLP-1s were “consistently associated” with a lower risk of developing SUDs, including those involving alcohol, cannabis, cocaine, nicotine, and opioids. The findings suggested “potential preventive effects across a broad range of addictive substances.”

In participants with pre-existing SUDs, GLP-1s were also associated with reduced risks of SUD-related emergency department visits, hospital admissions, and mortality, in addition to drug overdoses and suicidal behaviors. A study published in 2025 from the same research group reported that GLP-1s could have a variety of health benefits, including reducing the risk of incident alcohol and cannabis disorders, neurocognitive disorders (such as Alzheimer's disease and dementia), coagulation disorders, cardiometabolic disorders, infectious illnesses and several respiratory conditions, but less was known about the potential for preventing development of opioid use disorder and other SUDs. 

GLP-1s target the brain’s reward pathways and have recently made attention-grabbing headlines regarding celebrity weight loss, with social media boosting public interest. One study, for example, found 100 videos on TikTok with the #Ozempic viewed nearly 70 million times.

Al-Aly et al used SGLT-2 inhibitors as active comparators because “they have no established direct actions on mesolimbic reward circuits in the brain, whereas GLP-1 receptors are present in areas of the brain involved in impulse control and reward signaling.”

The second study found that quitting or pausing GLP-1 treatment for 6 months could have a rebound effect and possibly reverse any progress. Discontinuing GLP-1 treatment is common, with rates ranging from 36% to 81% in the first year. Stopping or interrupting the treatment is often followed by weight regain and a rebound in inflammation, both major drivers in cardiovascular disease risk. 

The study followed 132,551 VA patients using GLP-1s and 201,136 using sulfonylureas from 2017 through 2023. About two-thirds of participants took semaglutide, prescribed as Ozempic to treat diabetes and Wegovy to reduce obesity. A total of 26% of the participants stopped GLP-1 treatment during the follow-up period, with 64% occurring during the first year. Most (67%) treatment interruptions also came in the first year.

Compared with incident use of sulfonylureas, incident use of GLP-1s was associated with a reduced risk of heart attack, stroke, or death. Patients who took the GLP-1s without interruption > 3 years experienced an 18% lower risk for heart attack or stroke.  

Cardiovascular benefits accumulated with continuous use over 3 years, but even brief periods of discontinuations or interruptions could progressively erode and ultimately reverse this protection, the researchers found. Discontinuing treatment for half a year was associated with an increased risk of major adverse cardiovascular events (incidence risk ratio [IRR], 1.04), while longer gaps were progressively associated with a higher risk of disease (IRR, 1.12 for 1 year; IRR, 1.16 for 2 years of interrupted use, respectively).

Dr. Ziyad Al-Aly, a study author and Chief of the Research and Education Service at the Veterans Affairs Saint Louis Healthcare System, called it “metabolic whiplash.” In an interview, he said it was important to caution patients that these medications “need to be taken for the long haul. This is not something (patients) can take for a month or 2 or 3 and get off of it. It's not going to work like that.”

Recent research has revealed potential links between Agent Orange (AO) exposure and risk of acral melanoma (AM) among Vietnam War-era veterans, providing strong evidence of a relationship between the chemical and this type of cancer.

Localized to the palms, soles, and nail units, AM is a melanoma subtype less associated with UV radiation. From 1962 to 1971, the US military sprayed an estimated 18 million gallons of herbicides, including AO, over the fields and forests of Vietnam. Those herbicides have since been connected to numerous health issues, including cancer, though evidence of a relationship between AO and skin cancers has been weak. 

Vietnam War-era veterans have a higher melanoma burden than the general population, with the disease being the fourth-most common cancer among those who served. AM, however, is rare, representing about 2% to 3% of all melanomas. 

In a nested case-control study, Hwang et al used US Department of Veterans Affairs (VA) health care system data, including the VA Cancer Registry. The authors compared 1292 patients with AM and 2 pair-matched control groups: a group matched 4:1 to nonacral cutaneous melanoma controls, and a group without a melanoma diagnosis. 

Hwang et al found AO exposure was associated with increased odds of AM compared with each control group. In an accompanying editorial, Andrew Olshan, PhD, from Department of Epidemiology at the University of North Carolina Gillings School of Global Public Health, wrote, “The magnitude of the effects was modest (about 30%) but noteworthy.” 

A limitation of the study was that presumptive AOE status was based on whether the veteran filed a disability claim with evidence of officially recognized service in a period and place where Agent Orange was used—not on an assessment of the veteran’s individual AOE potential, including level of exposure. Because melanoma has never been included on the VA list of cancers presumed to be related to AO exposure, veterans do not automatically gain benefits by filing AOE claims after diagnosis. Even so, Olshan says, the reported study findings may underestimate the true effect of AO exposure on the risk of AM. 

Given the rarity of AM, the association (if causal) would translate to 0.4 to 0.8 new annual cases of AM per 1,000,000 veterans, according to the study. Narrowed down to Vietnam War-era veterans—who are dwindling in number—the attributable cases would be scarce.

Nevertheless, the search for a better understanding of a potential link between AOE and melanomas among Vietnam War-era veterans is important, Olshan wrote.

“The Hwang et al study provides a strong impetus to further these research goals and contribute to the investigation of the legacy of the Vietnam War and honor a commitment to the veterans community.”

Recent research has revealed potential links between Agent Orange (AO) exposure and risk of acral melanoma (AM) among Vietnam War-era veterans, providing strong evidence of a relationship between the chemical and this type of cancer.

Localized to the palms, soles, and nail units, AM is a melanoma subtype less associated with UV radiation. From 1962 to 1971, the US military sprayed an estimated 18 million gallons of herbicides, including AO, over the fields and forests of Vietnam. Those herbicides have since been connected to numerous health issues, including cancer, though evidence of a relationship between AO and skin cancers has been weak. 

Vietnam War-era veterans have a higher melanoma burden than the general population, with the disease being the fourth-most common cancer among those who served. AM, however, is rare, representing about 2% to 3% of all melanomas. 

In a nested case-control study, Hwang et al used US Department of Veterans Affairs (VA) health care system data, including the VA Cancer Registry. The authors compared 1292 patients with AM and 2 pair-matched control groups: a group matched 4:1 to nonacral cutaneous melanoma controls, and a group without a melanoma diagnosis. 

Hwang et al found AO exposure was associated with increased odds of AM compared with each control group. In an accompanying editorial, Andrew Olshan, PhD, from Department of Epidemiology at the University of North Carolina Gillings School of Global Public Health, wrote, “The magnitude of the effects was modest (about 30%) but noteworthy.” 

A limitation of the study was that presumptive AOE status was based on whether the veteran filed a disability claim with evidence of officially recognized service in a period and place where Agent Orange was used—not on an assessment of the veteran’s individual AOE potential, including level of exposure. Because melanoma has never been included on the VA list of cancers presumed to be related to AO exposure, veterans do not automatically gain benefits by filing AOE claims after diagnosis. Even so, Olshan says, the reported study findings may underestimate the true effect of AO exposure on the risk of AM. 

Given the rarity of AM, the association (if causal) would translate to 0.4 to 0.8 new annual cases of AM per 1,000,000 veterans, according to the study. Narrowed down to Vietnam War-era veterans—who are dwindling in number—the attributable cases would be scarce.

Nevertheless, the search for a better understanding of a potential link between AOE and melanomas among Vietnam War-era veterans is important, Olshan wrote.

“The Hwang et al study provides a strong impetus to further these research goals and contribute to the investigation of the legacy of the Vietnam War and honor a commitment to the veterans community.”

Recent research has revealed potential links between Agent Orange (AO) exposure and risk of acral melanoma (AM) among Vietnam War-era veterans, providing strong evidence of a relationship between the chemical and this type of cancer.

Localized to the palms, soles, and nail units, AM is a melanoma subtype less associated with UV radiation. From 1962 to 1971, the US military sprayed an estimated 18 million gallons of herbicides, including AO, over the fields and forests of Vietnam. Those herbicides have since been connected to numerous health issues, including cancer, though evidence of a relationship between AO and skin cancers has been weak. 

Vietnam War-era veterans have a higher melanoma burden than the general population, with the disease being the fourth-most common cancer among those who served. AM, however, is rare, representing about 2% to 3% of all melanomas. 

In a nested case-control study, Hwang et al used US Department of Veterans Affairs (VA) health care system data, including the VA Cancer Registry. The authors compared 1292 patients with AM and 2 pair-matched control groups: a group matched 4:1 to nonacral cutaneous melanoma controls, and a group without a melanoma diagnosis. 

Hwang et al found AO exposure was associated with increased odds of AM compared with each control group. In an accompanying editorial, Andrew Olshan, PhD, from Department of Epidemiology at the University of North Carolina Gillings School of Global Public Health, wrote, “The magnitude of the effects was modest (about 30%) but noteworthy.” 

A limitation of the study was that presumptive AOE status was based on whether the veteran filed a disability claim with evidence of officially recognized service in a period and place where Agent Orange was used—not on an assessment of the veteran’s individual AOE potential, including level of exposure. Because melanoma has never been included on the VA list of cancers presumed to be related to AO exposure, veterans do not automatically gain benefits by filing AOE claims after diagnosis. Even so, Olshan says, the reported study findings may underestimate the true effect of AO exposure on the risk of AM. 

Given the rarity of AM, the association (if causal) would translate to 0.4 to 0.8 new annual cases of AM per 1,000,000 veterans, according to the study. Narrowed down to Vietnam War-era veterans—who are dwindling in number—the attributable cases would be scarce.

Nevertheless, the search for a better understanding of a potential link between AOE and melanomas among Vietnam War-era veterans is important, Olshan wrote.

“The Hwang et al study provides a strong impetus to further these research goals and contribute to the investigation of the legacy of the Vietnam War and honor a commitment to the veterans community.”

SAN FRANCISCO – Peripheral T-cell lymphoma (PTCL) accounts for 4% of mature non-Hodgkin lymphoma cases in the US, or only about 4000 cases a year. While the number of patients is small, however, treatment for PTCL is complex due to wide variations in subtypes and survival rates, a hematologist-oncologist said at the March 21 Association of VA Hematology/Oncology (AVAHO) regional meeting on lymphoma.

Weiyun Ai, MD, PhD, a clinical professor of medicine at University of California, San Francisco who specializes in lymphoma, explained that there are multiple subtypes of PTCL based on their location within the body. Ai discussed a 2008 analysis of North American cases of PTCL and natural killer/T-cell lymphoma from 1990-2002, of which:

• 34% were PTCL, not otherwise specified;

• 16% were angioimmunoblastic T-cell lymphoma (AITL);

• 16% were anaplastic large cell lymphoma (ALCL), anaplastic lymphoma kinase (ALK)-positive;

• 7.8% were ALCL, ALK-negative;

• 5.8% were enteropathy-type;

• 5.4% were primary cutaneous ALCL; and

• 5.1% were extranodal natural killer/T-cell lymphoma, nasal type.

The remaining cases were adult T-cell leukemia/lymphoma, hepatosplenic, subcutaneous panniculitis-like, and unclassified. 

International Prognostic Index Predicts Outcomes

“The subtype with the best outcome is ALCL, ALK-positive with a 5-year overall survival rate of 70% followed by ALK-negative ALCL at 50%, and all the other common subtypes at 30%,” Ai said. 

Ai outlined the International Prognostic Index (IPI), a tool to predict clinical outcomes in patients with aggressive non-Hodgkin lymphoma based on risk factors. IPI assigns worse scores to patients aged > 60 years; patients who have higher (worse) performance scores, higher lactate dehydrogenase (LDH) levels, and more extranodal sites; and patients at stages III-IV.

First-Line Therapy: Consider Subtypes and CD30 Levels

Subtypes and CD30 expression levels are important factors in choosing therapy, Ai said, and 2019’s landmark ECHELON-2 study (updated in 2022) defines the standard. 

Newly diagnosed patients who strongly express CD30 (ie, those with both types of ALCL) are recommended to be treated with A+CHP (brentuximab vedotin [BV] plus cyclophosphamide, doxorubicin, and prednisone). 

Combination therapy of cyclophosphamide, doxorubicin, hydroxydaunorubicin, vincristine, and prednisone (CHOP) was the prior standard of care until the ECHELON-2 study, Ai said. 

That trial, which randomized 452 patients with untreated PTCL (CD30 ≥ 10%) to A+CHP or CHOP, found that 5-year progression-free rates were 51.4% vs 43.0%, respectively (hazard ratio [HR], 0.70; 95% CI, 0.53-0.91). Five-year overall survival rates were 70.1% vs. 61.0%, respectively (HR, 0.72; 95% CI, 0.53-0.99).

The threshold CD30 level at which to turn to A+CHP—1%, 5%, or 10%—“is kind of a dealer’s choice,” Ai said. Her own cutoff is 1%.

“If they're < 1%, I tend not to do it,” Ai said. “It's usually much more expensive, as you can imagine.”

If CD30 < 1%, Ai recommends CHOP or, in younger patients, CHOP plus etoposide (CHOEP).

Follow-up treatments include autologous stem cell transplant (ASCT) and observation/maintenance, depending on factors such as subtype, fitness, and remission.

Transplant: Still Relevant

When ECHELON-2 was released, some clinicians wondered if ASCT was still warranted, Ai said. A posthoc exploratory analysis found a 62% reduction in relative risk for progression in patients who underwent transplants after reaching complete remission with A+CHP. 

The findings provide support for transplant, she said. 

For transplant-ineligible patients, a small analysis of BV and CHP followed by BV maintenance showed a progression-free survival curve that appeared to plateau after 18-24 months.

“You don't see this kind of curve very often. I was quite impressed,” Ai said. “If the patient is willing and able, I will give them BV cycles.”

Ai discloses relationships with ADC, AbbVie, Acrotech, Kite, and Kyowa Kirin.

SAN FRANCISCO – Peripheral T-cell lymphoma (PTCL) accounts for 4% of mature non-Hodgkin lymphoma cases in the US, or only about 4000 cases a year. While the number of patients is small, however, treatment for PTCL is complex due to wide variations in subtypes and survival rates, a hematologist-oncologist said at the March 21 Association of VA Hematology/Oncology (AVAHO) regional meeting on lymphoma.

Weiyun Ai, MD, PhD, a clinical professor of medicine at University of California, San Francisco who specializes in lymphoma, explained that there are multiple subtypes of PTCL based on their location within the body. Ai discussed a 2008 analysis of North American cases of PTCL and natural killer/T-cell lymphoma from 1990-2002, of which:

• 34% were PTCL, not otherwise specified;

• 16% were angioimmunoblastic T-cell lymphoma (AITL);

• 16% were anaplastic large cell lymphoma (ALCL), anaplastic lymphoma kinase (ALK)-positive;

• 7.8% were ALCL, ALK-negative;

• 5.8% were enteropathy-type;

• 5.4% were primary cutaneous ALCL; and

• 5.1% were extranodal natural killer/T-cell lymphoma, nasal type.

The remaining cases were adult T-cell leukemia/lymphoma, hepatosplenic, subcutaneous panniculitis-like, and unclassified. 

International Prognostic Index Predicts Outcomes

“The subtype with the best outcome is ALCL, ALK-positive with a 5-year overall survival rate of 70% followed by ALK-negative ALCL at 50%, and all the other common subtypes at 30%,” Ai said. 

Ai outlined the International Prognostic Index (IPI), a tool to predict clinical outcomes in patients with aggressive non-Hodgkin lymphoma based on risk factors. IPI assigns worse scores to patients aged > 60 years; patients who have higher (worse) performance scores, higher lactate dehydrogenase (LDH) levels, and more extranodal sites; and patients at stages III-IV.

First-Line Therapy: Consider Subtypes and CD30 Levels

Subtypes and CD30 expression levels are important factors in choosing therapy, Ai said, and 2019’s landmark ECHELON-2 study (updated in 2022) defines the standard. 

Newly diagnosed patients who strongly express CD30 (ie, those with both types of ALCL) are recommended to be treated with A+CHP (brentuximab vedotin [BV] plus cyclophosphamide, doxorubicin, and prednisone). 

Combination therapy of cyclophosphamide, doxorubicin, hydroxydaunorubicin, vincristine, and prednisone (CHOP) was the prior standard of care until the ECHELON-2 study, Ai said. 

That trial, which randomized 452 patients with untreated PTCL (CD30 ≥ 10%) to A+CHP or CHOP, found that 5-year progression-free rates were 51.4% vs 43.0%, respectively (hazard ratio [HR], 0.70; 95% CI, 0.53-0.91). Five-year overall survival rates were 70.1% vs. 61.0%, respectively (HR, 0.72; 95% CI, 0.53-0.99).

The threshold CD30 level at which to turn to A+CHP—1%, 5%, or 10%—“is kind of a dealer’s choice,” Ai said. Her own cutoff is 1%.

“If they're < 1%, I tend not to do it,” Ai said. “It's usually much more expensive, as you can imagine.”

If CD30 < 1%, Ai recommends CHOP or, in younger patients, CHOP plus etoposide (CHOEP).

Follow-up treatments include autologous stem cell transplant (ASCT) and observation/maintenance, depending on factors such as subtype, fitness, and remission.

Transplant: Still Relevant

When ECHELON-2 was released, some clinicians wondered if ASCT was still warranted, Ai said. A posthoc exploratory analysis found a 62% reduction in relative risk for progression in patients who underwent transplants after reaching complete remission with A+CHP. 

The findings provide support for transplant, she said. 

For transplant-ineligible patients, a small analysis of BV and CHP followed by BV maintenance showed a progression-free survival curve that appeared to plateau after 18-24 months.

“You don't see this kind of curve very often. I was quite impressed,” Ai said. “If the patient is willing and able, I will give them BV cycles.”

Ai discloses relationships with ADC, AbbVie, Acrotech, Kite, and Kyowa Kirin.

SAN FRANCISCO – Peripheral T-cell lymphoma (PTCL) accounts for 4% of mature non-Hodgkin lymphoma cases in the US, or only about 4000 cases a year. While the number of patients is small, however, treatment for PTCL is complex due to wide variations in subtypes and survival rates, a hematologist-oncologist said at the March 21 Association of VA Hematology/Oncology (AVAHO) regional meeting on lymphoma.

Weiyun Ai, MD, PhD, a clinical professor of medicine at University of California, San Francisco who specializes in lymphoma, explained that there are multiple subtypes of PTCL based on their location within the body. Ai discussed a 2008 analysis of North American cases of PTCL and natural killer/T-cell lymphoma from 1990-2002, of which:

• 34% were PTCL, not otherwise specified;

• 16% were angioimmunoblastic T-cell lymphoma (AITL);

• 16% were anaplastic large cell lymphoma (ALCL), anaplastic lymphoma kinase (ALK)-positive;

• 7.8% were ALCL, ALK-negative;

• 5.8% were enteropathy-type;

• 5.4% were primary cutaneous ALCL; and

• 5.1% were extranodal natural killer/T-cell lymphoma, nasal type.

The remaining cases were adult T-cell leukemia/lymphoma, hepatosplenic, subcutaneous panniculitis-like, and unclassified. 

International Prognostic Index Predicts Outcomes

“The subtype with the best outcome is ALCL, ALK-positive with a 5-year overall survival rate of 70% followed by ALK-negative ALCL at 50%, and all the other common subtypes at 30%,” Ai said. 

Ai outlined the International Prognostic Index (IPI), a tool to predict clinical outcomes in patients with aggressive non-Hodgkin lymphoma based on risk factors. IPI assigns worse scores to patients aged > 60 years; patients who have higher (worse) performance scores, higher lactate dehydrogenase (LDH) levels, and more extranodal sites; and patients at stages III-IV.

First-Line Therapy: Consider Subtypes and CD30 Levels

Subtypes and CD30 expression levels are important factors in choosing therapy, Ai said, and 2019’s landmark ECHELON-2 study (updated in 2022) defines the standard. 

Newly diagnosed patients who strongly express CD30 (ie, those with both types of ALCL) are recommended to be treated with A+CHP (brentuximab vedotin [BV] plus cyclophosphamide, doxorubicin, and prednisone). 

Combination therapy of cyclophosphamide, doxorubicin, hydroxydaunorubicin, vincristine, and prednisone (CHOP) was the prior standard of care until the ECHELON-2 study, Ai said. 

That trial, which randomized 452 patients with untreated PTCL (CD30 ≥ 10%) to A+CHP or CHOP, found that 5-year progression-free rates were 51.4% vs 43.0%, respectively (hazard ratio [HR], 0.70; 95% CI, 0.53-0.91). Five-year overall survival rates were 70.1% vs. 61.0%, respectively (HR, 0.72; 95% CI, 0.53-0.99).

The threshold CD30 level at which to turn to A+CHP—1%, 5%, or 10%—“is kind of a dealer’s choice,” Ai said. Her own cutoff is 1%.

“If they're < 1%, I tend not to do it,” Ai said. “It's usually much more expensive, as you can imagine.”

If CD30 < 1%, Ai recommends CHOP or, in younger patients, CHOP plus etoposide (CHOEP).

Follow-up treatments include autologous stem cell transplant (ASCT) and observation/maintenance, depending on factors such as subtype, fitness, and remission.

Transplant: Still Relevant

When ECHELON-2 was released, some clinicians wondered if ASCT was still warranted, Ai said. A posthoc exploratory analysis found a 62% reduction in relative risk for progression in patients who underwent transplants after reaching complete remission with A+CHP. 

The findings provide support for transplant, she said. 

For transplant-ineligible patients, a small analysis of BV and CHP followed by BV maintenance showed a progression-free survival curve that appeared to plateau after 18-24 months.

“You don't see this kind of curve very often. I was quite impressed,” Ai said. “If the patient is willing and able, I will give them BV cycles.”

Ai discloses relationships with ADC, AbbVie, Acrotech, Kite, and Kyowa Kirin.