B Cell Lymphoma

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Largest data set to date

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

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

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

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

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

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

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

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

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

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

The results were also published in The Lancet.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Largest data set to date

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

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

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

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

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

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

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

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

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

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

The results were also published in The Lancet.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Largest data set to date

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

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

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

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

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

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

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

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

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

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

The results were also published in The Lancet.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Novel therapies have transformed the management of chronic lymphocytic leukemia (CLL) over the past decade. With the advent of new options, the optimal therapy for newly diagnosed patients has become less clear. Bruton tyrosine kinase (BTK) inhibitors have led to improvement in outcomes for most patients with CLL compared with chemoimmunotherapy (CIT).^1,2 Second-generation BTK inhibitors, such as acalabrutinib and zanubrutinib, are also available and appear to have an improved safety profile compared with ibrutinib. Similarly, the B-cell lymphoma 2 (BCL2) inhibitor venetoclax, in combination with obinutuzumab, is an effective option in first-line treatment that offers a time-limited approach.³ Studies combining BTK and BCL2 inhibitors are also promising in this setting.

Recently, the phase 3 GAIA-CLL13 study aimed to address the question of optimal time-limited first-line treatment for fit patients with CLL. Of note, patients with TP53 aberrations were excluded. Patients were randomly assigned to one of four treatment arms: CIT (fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab), venetoclax-obinutuzumab, venetoclax-rituximab, or venetoclax-obinutuzumab-ibrutinub.

At 15 months, the rate of undetectable minimal residual disease (uMRD) was higher in the venetoclax-obinutuzumab group (86.5%; 97.5% CI 80.6-91.1) and the venetoclax-obinutuzumab-ibrutinib group (92.2%; 97.5% CI 87.3-95.7) compared with the CIT group (52.0%; 97.5% CI 44.4-59.5; P < .001 for both comparisons). The rate of uMRD for the venetoclax-rituximab group, however, was not higher than the rate in the CIT group (57.0%; 97.5%, CI 49.5-64.2; P = .32). The 3-year progression-free survival (PFS) was 90.5% in the venetoclax-obinutuzumab-ibrutinib group and 75.5% in the CIT group (hazard ratio [HR] for disease progression or death 0.32; 97.5% CI 0.19-0.54; P < .001). PFS at 3 years was also higher in the venetoclax-obinutuzumab group (87.7%; HR for disease progression or death, 0.42; 97.5% CI 0.26-0.68; P < .001), but not with venetoclax-rituximab group (80.8%; HR 0.79; 97.5% CI 0.53-1.18; P = .18). Grade 3 and grade 4 infections were more common with CIT (18.5%) and venetoclax-obinutuzumab-ibrutinib (21.2%) than with venetoclax-rituximab (10.5%) or venetoclax-obinutuzumab (13.2%).

This study confirms the role of fixed-duration venetoclax-based therapy for younger, fit patients with CLL. Interestingly, this study also suggests that rates of uMRD and PFS are superior with the use of obinutuzumab rather than with rituximab. Also of note, though the uMRD and PFS were highest with the triplet combination, it was not clearly superior to venetoclax-obinutuzumab alone and was associated with greater rates of toxicity.

Another ongoing randomized trial in first-line treatment of CLL is the FLAIR trial. This study was initially designed to compare ibrutinib-rituximab with standard CIT, though it was later modified to include an arm of ibrutinib alone and ibrutinib-venetoclax. Recently, the results of the first formal interim analysis comparing fludarabine, cyclophosphamide, and rituximab (n = 385) to ibrutinib-rituximb (n = 386), were published. This study, like the ECOG1912 study², demonstrated improved outcomes with a BTK inhibitor over standard CIT in fit patients with CLL. After a median follow-up of 53 months, the median PFS was not reached in patients receiving ibrutinib-rituximab and was 67 months (95% CI 63 to not reached) in those receiving fludarabine, cyclophosphamide, and rituximab (HR 0.44; P < .0001). A substantial number of sudden cardiac or unexplained deaths occurred, which were more frequent in the ibrutinib-rituximab group.

Though questions regarding optimal treatment remain, there are now multiple studies to suggest an advantage of novel agents over traditional CIT. Furthermore, regardless of approach, outcomes appear favorable for patients with CLL, even among higher-risk patients.

Other studies are also evaluating alternative ways to sequence therapy. A recent phase 2 study, for example, evaluated venetoclax consolidation for patients on ibrutinib. Forty-five patients with CLL and detectable disease (≥ 0.01% minimal residual disease in bone marrow [BM]) after treatment with ibrutinib for 12 or more months who had one or more high-risk feature for disease progression were included. Patients received combined treatment with ibrutinib (previously tolerated dose) and venetoclax (escalated to 400 mg once daily) for 24 or less cycles. Venetoclax was continued until patients achieved uMRD. Patients with uMRD also had the option of discontinuing ibrutinib. Adding venetoclax to ibrutinib led to a cumulative BM uMRD rate of 73%. BM uMRD was achieved by 71% of patients after venetoclax therapy completion and by 38% and 57% of patients after 6 and 12 cycles, respectively. This trial highlights the potential use of MRD to guide treatment as well as consolidation strategies to allow for time-limited treatment.

Additional References

1. Woyach JA, Ruppert AS, Heerema NA, et al. Ibrutinib regimens versus chemoimmunotherapy in older patients with untreated CLL. N Engl J Med. 2018;379:2517-2528. doi: 10.1056/NEJMoa1812836
2. Shanafelt TD, Wang XV, Kay NE, et al. Ibrutinib-rituximab or chemoimmunotherapy for chronic lymphocytic leukemia. N Engl J Med. 2019;381:432-443. doi: 10.1056/NEJMoa1817073
3. Fischer K, Al-Sawaf O, Bahlo J, et al. Venetoclax and obinutuzumab in patients with CLL and coexisting conditions. N Engl J Med. 2019;380:2225-2236. doi: 10.1056/NEJMoa1815281

Novel therapies have transformed the management of chronic lymphocytic leukemia (CLL) over the past decade. With the advent of new options, the optimal therapy for newly diagnosed patients has become less clear. Bruton tyrosine kinase (BTK) inhibitors have led to improvement in outcomes for most patients with CLL compared with chemoimmunotherapy (CIT).^1,2 Second-generation BTK inhibitors, such as acalabrutinib and zanubrutinib, are also available and appear to have an improved safety profile compared with ibrutinib. Similarly, the B-cell lymphoma 2 (BCL2) inhibitor venetoclax, in combination with obinutuzumab, is an effective option in first-line treatment that offers a time-limited approach.³ Studies combining BTK and BCL2 inhibitors are also promising in this setting.

Recently, the phase 3 GAIA-CLL13 study aimed to address the question of optimal time-limited first-line treatment for fit patients with CLL. Of note, patients with TP53 aberrations were excluded. Patients were randomly assigned to one of four treatment arms: CIT (fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab), venetoclax-obinutuzumab, venetoclax-rituximab, or venetoclax-obinutuzumab-ibrutinub.

At 15 months, the rate of undetectable minimal residual disease (uMRD) was higher in the venetoclax-obinutuzumab group (86.5%; 97.5% CI 80.6-91.1) and the venetoclax-obinutuzumab-ibrutinib group (92.2%; 97.5% CI 87.3-95.7) compared with the CIT group (52.0%; 97.5% CI 44.4-59.5; P < .001 for both comparisons). The rate of uMRD for the venetoclax-rituximab group, however, was not higher than the rate in the CIT group (57.0%; 97.5%, CI 49.5-64.2; P = .32). The 3-year progression-free survival (PFS) was 90.5% in the venetoclax-obinutuzumab-ibrutinib group and 75.5% in the CIT group (hazard ratio [HR] for disease progression or death 0.32; 97.5% CI 0.19-0.54; P < .001). PFS at 3 years was also higher in the venetoclax-obinutuzumab group (87.7%; HR for disease progression or death, 0.42; 97.5% CI 0.26-0.68; P < .001), but not with venetoclax-rituximab group (80.8%; HR 0.79; 97.5% CI 0.53-1.18; P = .18). Grade 3 and grade 4 infections were more common with CIT (18.5%) and venetoclax-obinutuzumab-ibrutinib (21.2%) than with venetoclax-rituximab (10.5%) or venetoclax-obinutuzumab (13.2%).

This study confirms the role of fixed-duration venetoclax-based therapy for younger, fit patients with CLL. Interestingly, this study also suggests that rates of uMRD and PFS are superior with the use of obinutuzumab rather than with rituximab. Also of note, though the uMRD and PFS were highest with the triplet combination, it was not clearly superior to venetoclax-obinutuzumab alone and was associated with greater rates of toxicity.

Another ongoing randomized trial in first-line treatment of CLL is the FLAIR trial. This study was initially designed to compare ibrutinib-rituximab with standard CIT, though it was later modified to include an arm of ibrutinib alone and ibrutinib-venetoclax. Recently, the results of the first formal interim analysis comparing fludarabine, cyclophosphamide, and rituximab (n = 385) to ibrutinib-rituximb (n = 386), were published. This study, like the ECOG1912 study², demonstrated improved outcomes with a BTK inhibitor over standard CIT in fit patients with CLL. After a median follow-up of 53 months, the median PFS was not reached in patients receiving ibrutinib-rituximab and was 67 months (95% CI 63 to not reached) in those receiving fludarabine, cyclophosphamide, and rituximab (HR 0.44; P < .0001). A substantial number of sudden cardiac or unexplained deaths occurred, which were more frequent in the ibrutinib-rituximab group.

Though questions regarding optimal treatment remain, there are now multiple studies to suggest an advantage of novel agents over traditional CIT. Furthermore, regardless of approach, outcomes appear favorable for patients with CLL, even among higher-risk patients.

Other studies are also evaluating alternative ways to sequence therapy. A recent phase 2 study, for example, evaluated venetoclax consolidation for patients on ibrutinib. Forty-five patients with CLL and detectable disease (≥ 0.01% minimal residual disease in bone marrow [BM]) after treatment with ibrutinib for 12 or more months who had one or more high-risk feature for disease progression were included. Patients received combined treatment with ibrutinib (previously tolerated dose) and venetoclax (escalated to 400 mg once daily) for 24 or less cycles. Venetoclax was continued until patients achieved uMRD. Patients with uMRD also had the option of discontinuing ibrutinib. Adding venetoclax to ibrutinib led to a cumulative BM uMRD rate of 73%. BM uMRD was achieved by 71% of patients after venetoclax therapy completion and by 38% and 57% of patients after 6 and 12 cycles, respectively. This trial highlights the potential use of MRD to guide treatment as well as consolidation strategies to allow for time-limited treatment.

Additional References

1. Woyach JA, Ruppert AS, Heerema NA, et al. Ibrutinib regimens versus chemoimmunotherapy in older patients with untreated CLL. N Engl J Med. 2018;379:2517-2528. doi: 10.1056/NEJMoa1812836
2. Shanafelt TD, Wang XV, Kay NE, et al. Ibrutinib-rituximab or chemoimmunotherapy for chronic lymphocytic leukemia. N Engl J Med. 2019;381:432-443. doi: 10.1056/NEJMoa1817073
3. Fischer K, Al-Sawaf O, Bahlo J, et al. Venetoclax and obinutuzumab in patients with CLL and coexisting conditions. N Engl J Med. 2019;380:2225-2236. doi: 10.1056/NEJMoa1815281

Novel therapies have transformed the management of chronic lymphocytic leukemia (CLL) over the past decade. With the advent of new options, the optimal therapy for newly diagnosed patients has become less clear. Bruton tyrosine kinase (BTK) inhibitors have led to improvement in outcomes for most patients with CLL compared with chemoimmunotherapy (CIT).^1,2 Second-generation BTK inhibitors, such as acalabrutinib and zanubrutinib, are also available and appear to have an improved safety profile compared with ibrutinib. Similarly, the B-cell lymphoma 2 (BCL2) inhibitor venetoclax, in combination with obinutuzumab, is an effective option in first-line treatment that offers a time-limited approach.³ Studies combining BTK and BCL2 inhibitors are also promising in this setting.

Recently, the phase 3 GAIA-CLL13 study aimed to address the question of optimal time-limited first-line treatment for fit patients with CLL. Of note, patients with TP53 aberrations were excluded. Patients were randomly assigned to one of four treatment arms: CIT (fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab), venetoclax-obinutuzumab, venetoclax-rituximab, or venetoclax-obinutuzumab-ibrutinub.

At 15 months, the rate of undetectable minimal residual disease (uMRD) was higher in the venetoclax-obinutuzumab group (86.5%; 97.5% CI 80.6-91.1) and the venetoclax-obinutuzumab-ibrutinib group (92.2%; 97.5% CI 87.3-95.7) compared with the CIT group (52.0%; 97.5% CI 44.4-59.5; P < .001 for both comparisons). The rate of uMRD for the venetoclax-rituximab group, however, was not higher than the rate in the CIT group (57.0%; 97.5%, CI 49.5-64.2; P = .32). The 3-year progression-free survival (PFS) was 90.5% in the venetoclax-obinutuzumab-ibrutinib group and 75.5% in the CIT group (hazard ratio [HR] for disease progression or death 0.32; 97.5% CI 0.19-0.54; P < .001). PFS at 3 years was also higher in the venetoclax-obinutuzumab group (87.7%; HR for disease progression or death, 0.42; 97.5% CI 0.26-0.68; P < .001), but not with venetoclax-rituximab group (80.8%; HR 0.79; 97.5% CI 0.53-1.18; P = .18). Grade 3 and grade 4 infections were more common with CIT (18.5%) and venetoclax-obinutuzumab-ibrutinib (21.2%) than with venetoclax-rituximab (10.5%) or venetoclax-obinutuzumab (13.2%).

This study confirms the role of fixed-duration venetoclax-based therapy for younger, fit patients with CLL. Interestingly, this study also suggests that rates of uMRD and PFS are superior with the use of obinutuzumab rather than with rituximab. Also of note, though the uMRD and PFS were highest with the triplet combination, it was not clearly superior to venetoclax-obinutuzumab alone and was associated with greater rates of toxicity.

Another ongoing randomized trial in first-line treatment of CLL is the FLAIR trial. This study was initially designed to compare ibrutinib-rituximab with standard CIT, though it was later modified to include an arm of ibrutinib alone and ibrutinib-venetoclax. Recently, the results of the first formal interim analysis comparing fludarabine, cyclophosphamide, and rituximab (n = 385) to ibrutinib-rituximb (n = 386), were published. This study, like the ECOG1912 study², demonstrated improved outcomes with a BTK inhibitor over standard CIT in fit patients with CLL. After a median follow-up of 53 months, the median PFS was not reached in patients receiving ibrutinib-rituximab and was 67 months (95% CI 63 to not reached) in those receiving fludarabine, cyclophosphamide, and rituximab (HR 0.44; P < .0001). A substantial number of sudden cardiac or unexplained deaths occurred, which were more frequent in the ibrutinib-rituximab group.

Though questions regarding optimal treatment remain, there are now multiple studies to suggest an advantage of novel agents over traditional CIT. Furthermore, regardless of approach, outcomes appear favorable for patients with CLL, even among higher-risk patients.

Other studies are also evaluating alternative ways to sequence therapy. A recent phase 2 study, for example, evaluated venetoclax consolidation for patients on ibrutinib. Forty-five patients with CLL and detectable disease (≥ 0.01% minimal residual disease in bone marrow [BM]) after treatment with ibrutinib for 12 or more months who had one or more high-risk feature for disease progression were included. Patients received combined treatment with ibrutinib (previously tolerated dose) and venetoclax (escalated to 400 mg once daily) for 24 or less cycles. Venetoclax was continued until patients achieved uMRD. Patients with uMRD also had the option of discontinuing ibrutinib. Adding venetoclax to ibrutinib led to a cumulative BM uMRD rate of 73%. BM uMRD was achieved by 71% of patients after venetoclax therapy completion and by 38% and 57% of patients after 6 and 12 cycles, respectively. This trial highlights the potential use of MRD to guide treatment as well as consolidation strategies to allow for time-limited treatment.

Additional References

1. Woyach JA, Ruppert AS, Heerema NA, et al. Ibrutinib regimens versus chemoimmunotherapy in older patients with untreated CLL. N Engl J Med. 2018;379:2517-2528. doi: 10.1056/NEJMoa1812836
2. Shanafelt TD, Wang XV, Kay NE, et al. Ibrutinib-rituximab or chemoimmunotherapy for chronic lymphocytic leukemia. N Engl J Med. 2019;381:432-443. doi: 10.1056/NEJMoa1817073
3. Fischer K, Al-Sawaf O, Bahlo J, et al. Venetoclax and obinutuzumab in patients with CLL and coexisting conditions. N Engl J Med. 2019;380:2225-2236. doi: 10.1056/NEJMoa1815281

The U.S. Food and Drug Administration approved epcoritamab-bysp (Epkinly, AbbVie and Genmab) today for adults with relapsed/refractory diffuse large B-cell lymphoma following at least two lines of systemic therapy. This includes patients with DLBCL arising from indolent lymphoma and high-grade B-cell lymphoma.

Epcoritamab is the first subcutaneous bispecific antibody approved for the indication. The biologic simultaneously binds CD3 on cytotoxic T cells to CD20 on lymphomic B cells, inducing T-cell mediated destruction.

“Together with our partner, AbbVie, we recognize the unmet need for safe, effective, and accessible treatments for patients with B-cell malignancies and we believe that epcoritamab has the potential to become a core therapy in this patient population,” Jan van de Winkel, PhD, CEO of Genmab, said in a press release announcing the FDA’s acceptance of its biologic licensing application in November 2022.

A potential competitor, Roche’s bispecific antibody mosunetuzumab (Lunsumio), was approved in December 2022. Mosunetuzumab has the same mechanism of action as epcoritamab but is indicated for relapsed or refractory follicular lymphoma after at least two lines of systemic therapy. A phase 3 trial is currently underway exploring epcoritamab for relapsed or refractory follicular lymphoma as part of combination therapy.

The current approval was based on the open-label phase 2 EPCORE NHL-1 trial conducted by AbbVie and Genmab. The trial’s efficacy population included 148 adults with relapsed or refractory CD20+ large B-cell lymphoma who had received at least two prior lines of therapy, including anti-CD20 therapies. Almost 40% had undergone CAR-T cell therapy.

Epcoritamab was administered initially once weekly, then every 2 weeks, and then every 4 weeks until disease progression or unacceptable toxicity. The trial had no comparator arm.

At a median follow-up of 10.7 months, the overall response rate was 61% and the complete response rate was 38%. At a median follow-up of 9.8 months among responders, the median duration of response was 15.6 months.

The prescribing information comes with a boxed warning for serious or life-threatening cytokine release syndrome and life-threatening or fatal immune effector cell–associated neurotoxicity syndrome. Warnings and precautions include infections and cytopenias.

Among the 157 patients who received epcoritamab in the trial at the recommended dose, grade 1-3 cytokine release syndrome occurred in 51%, immune effector cell–associated neurotoxicity syndrome occurred in 6% (with one fatal case), and 15% experienced serious infections.

The most common grade 3 or 4 events included neutropenia (14.6%), anemia (10.2%), and thrombocytopenia (5.7%).

The FDA recommends epcoritamab be administered subcutaneously in 28-day cycles until disease progression or unacceptable toxicity.

The FDA also noted that “this indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.”
 

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

The U.S. Food and Drug Administration approved epcoritamab-bysp (Epkinly, AbbVie and Genmab) today for adults with relapsed/refractory diffuse large B-cell lymphoma following at least two lines of systemic therapy. This includes patients with DLBCL arising from indolent lymphoma and high-grade B-cell lymphoma.

Epcoritamab is the first subcutaneous bispecific antibody approved for the indication. The biologic simultaneously binds CD3 on cytotoxic T cells to CD20 on lymphomic B cells, inducing T-cell mediated destruction.

“Together with our partner, AbbVie, we recognize the unmet need for safe, effective, and accessible treatments for patients with B-cell malignancies and we believe that epcoritamab has the potential to become a core therapy in this patient population,” Jan van de Winkel, PhD, CEO of Genmab, said in a press release announcing the FDA’s acceptance of its biologic licensing application in November 2022.

A potential competitor, Roche’s bispecific antibody mosunetuzumab (Lunsumio), was approved in December 2022. Mosunetuzumab has the same mechanism of action as epcoritamab but is indicated for relapsed or refractory follicular lymphoma after at least two lines of systemic therapy. A phase 3 trial is currently underway exploring epcoritamab for relapsed or refractory follicular lymphoma as part of combination therapy.

The current approval was based on the open-label phase 2 EPCORE NHL-1 trial conducted by AbbVie and Genmab. The trial’s efficacy population included 148 adults with relapsed or refractory CD20+ large B-cell lymphoma who had received at least two prior lines of therapy, including anti-CD20 therapies. Almost 40% had undergone CAR-T cell therapy.

Epcoritamab was administered initially once weekly, then every 2 weeks, and then every 4 weeks until disease progression or unacceptable toxicity. The trial had no comparator arm.

At a median follow-up of 10.7 months, the overall response rate was 61% and the complete response rate was 38%. At a median follow-up of 9.8 months among responders, the median duration of response was 15.6 months.

The prescribing information comes with a boxed warning for serious or life-threatening cytokine release syndrome and life-threatening or fatal immune effector cell–associated neurotoxicity syndrome. Warnings and precautions include infections and cytopenias.

Among the 157 patients who received epcoritamab in the trial at the recommended dose, grade 1-3 cytokine release syndrome occurred in 51%, immune effector cell–associated neurotoxicity syndrome occurred in 6% (with one fatal case), and 15% experienced serious infections.

The most common grade 3 or 4 events included neutropenia (14.6%), anemia (10.2%), and thrombocytopenia (5.7%).

The FDA recommends epcoritamab be administered subcutaneously in 28-day cycles until disease progression or unacceptable toxicity.

The FDA also noted that “this indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.”
 

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

The U.S. Food and Drug Administration approved epcoritamab-bysp (Epkinly, AbbVie and Genmab) today for adults with relapsed/refractory diffuse large B-cell lymphoma following at least two lines of systemic therapy. This includes patients with DLBCL arising from indolent lymphoma and high-grade B-cell lymphoma.

Epcoritamab is the first subcutaneous bispecific antibody approved for the indication. The biologic simultaneously binds CD3 on cytotoxic T cells to CD20 on lymphomic B cells, inducing T-cell mediated destruction.

“Together with our partner, AbbVie, we recognize the unmet need for safe, effective, and accessible treatments for patients with B-cell malignancies and we believe that epcoritamab has the potential to become a core therapy in this patient population,” Jan van de Winkel, PhD, CEO of Genmab, said in a press release announcing the FDA’s acceptance of its biologic licensing application in November 2022.

A potential competitor, Roche’s bispecific antibody mosunetuzumab (Lunsumio), was approved in December 2022. Mosunetuzumab has the same mechanism of action as epcoritamab but is indicated for relapsed or refractory follicular lymphoma after at least two lines of systemic therapy. A phase 3 trial is currently underway exploring epcoritamab for relapsed or refractory follicular lymphoma as part of combination therapy.

The current approval was based on the open-label phase 2 EPCORE NHL-1 trial conducted by AbbVie and Genmab. The trial’s efficacy population included 148 adults with relapsed or refractory CD20+ large B-cell lymphoma who had received at least two prior lines of therapy, including anti-CD20 therapies. Almost 40% had undergone CAR-T cell therapy.

Epcoritamab was administered initially once weekly, then every 2 weeks, and then every 4 weeks until disease progression or unacceptable toxicity. The trial had no comparator arm.

At a median follow-up of 10.7 months, the overall response rate was 61% and the complete response rate was 38%. At a median follow-up of 9.8 months among responders, the median duration of response was 15.6 months.

The prescribing information comes with a boxed warning for serious or life-threatening cytokine release syndrome and life-threatening or fatal immune effector cell–associated neurotoxicity syndrome. Warnings and precautions include infections and cytopenias.

Among the 157 patients who received epcoritamab in the trial at the recommended dose, grade 1-3 cytokine release syndrome occurred in 51%, immune effector cell–associated neurotoxicity syndrome occurred in 6% (with one fatal case), and 15% experienced serious infections.

The most common grade 3 or 4 events included neutropenia (14.6%), anemia (10.2%), and thrombocytopenia (5.7%).

The FDA recommends epcoritamab be administered subcutaneously in 28-day cycles until disease progression or unacceptable toxicity.

The FDA also noted that “this indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.”
 

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

Key clinical point: Pembrolizumab offers potent and sustained efficacy with an acceptable safety profile in heavily pretreated patients with relapsed or refractory primary mediastinal B-cell lymphoma (PMBCL).

Major finding: After a median follow-up of 48.7 months, the median progression-free survival and overall survival were 4.3 (95% CI 2.8-13.8) months and 22.3 (95% CI 7.3-not reached) months, respectively. The objective response rate was 41.5%. Grade 3 or 4 treatment-related adverse events occurred in 22.6% of patients.

Study details: Findings are from the final analysis of the phase 2 KEYNOTE-170 trial including 53 adult patients with relapsed or refractory PMBCL whose disease progressed after or who were ineligible for (after ≥2 prior lines of therapy) autologous stem cell transplantation and received pembrolizumab every 3 weeks for up to 2 years.

Disclosures: The KEYNOTE-170 trial was funded by Merck Sharp & Dohme (MSD). Some authors reported ties with various organizations, including MSD. Three authors declared being employees of and holding stock or stock options in MSD.

Source: Zinzani PL et al. Pembrolizumab in relapsed or refractory primary mediastinal large B-cell lymphoma: Final analysis of KEYNOTE-170. Blood. 2023 (May 2). Doi: 10.1182/blood.2022019340

Key clinical point: Pembrolizumab offers potent and sustained efficacy with an acceptable safety profile in heavily pretreated patients with relapsed or refractory primary mediastinal B-cell lymphoma (PMBCL).

Major finding: After a median follow-up of 48.7 months, the median progression-free survival and overall survival were 4.3 (95% CI 2.8-13.8) months and 22.3 (95% CI 7.3-not reached) months, respectively. The objective response rate was 41.5%. Grade 3 or 4 treatment-related adverse events occurred in 22.6% of patients.

Study details: Findings are from the final analysis of the phase 2 KEYNOTE-170 trial including 53 adult patients with relapsed or refractory PMBCL whose disease progressed after or who were ineligible for (after ≥2 prior lines of therapy) autologous stem cell transplantation and received pembrolizumab every 3 weeks for up to 2 years.

Disclosures: The KEYNOTE-170 trial was funded by Merck Sharp & Dohme (MSD). Some authors reported ties with various organizations, including MSD. Three authors declared being employees of and holding stock or stock options in MSD.

Source: Zinzani PL et al. Pembrolizumab in relapsed or refractory primary mediastinal large B-cell lymphoma: Final analysis of KEYNOTE-170. Blood. 2023 (May 2). Doi: 10.1182/blood.2022019340

Key clinical point: Pembrolizumab offers potent and sustained efficacy with an acceptable safety profile in heavily pretreated patients with relapsed or refractory primary mediastinal B-cell lymphoma (PMBCL).

Major finding: After a median follow-up of 48.7 months, the median progression-free survival and overall survival were 4.3 (95% CI 2.8-13.8) months and 22.3 (95% CI 7.3-not reached) months, respectively. The objective response rate was 41.5%. Grade 3 or 4 treatment-related adverse events occurred in 22.6% of patients.

Study details: Findings are from the final analysis of the phase 2 KEYNOTE-170 trial including 53 adult patients with relapsed or refractory PMBCL whose disease progressed after or who were ineligible for (after ≥2 prior lines of therapy) autologous stem cell transplantation and received pembrolizumab every 3 weeks for up to 2 years.

Disclosures: The KEYNOTE-170 trial was funded by Merck Sharp & Dohme (MSD). Some authors reported ties with various organizations, including MSD. Three authors declared being employees of and holding stock or stock options in MSD.

Source: Zinzani PL et al. Pembrolizumab in relapsed or refractory primary mediastinal large B-cell lymphoma: Final analysis of KEYNOTE-170. Blood. 2023 (May 2). Doi: 10.1182/blood.2022019340

Key clinical point: Among patients with diffuse large B-cell lymphoma (DLBCL) who do not complete the recommended six cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) combination chemotherapy, those who do vs do not achieve primary response or complete ≥3 chemotherapy cycles have better survival.

Major finding: The 5-year overall survival rate was significantly higher in patients who did vs did not complete ≥3 cycles of R-CHOP (58.5% vs 24.2%; P < .001) and in those who did vs did not achieve complete or partial response after R-CHOP (56.9% vs 14.1%; P < .001).

Study details: Findings are from a single-center real-world retrospective study including 165 patients with DLBCL who did not receive the planned 6 cycles of R-CHOP.

Disclosures: No information on the source of funding was provided. SS Yoon declared serving as an advisor for and receiving research grants from various organizations.

Source: Yoon J et al. Clinical outcomes after incomplete cycles of R-CHOP for diffuse large B-cell lymphoma: 10 years' real-world experience in a single institute. Ann Hematol. 2023;102:1467-1476 (Apr 26). Doi: 10.1007/s00277-023-05179-5

Key clinical point: Among patients with diffuse large B-cell lymphoma (DLBCL) who do not complete the recommended six cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) combination chemotherapy, those who do vs do not achieve primary response or complete ≥3 chemotherapy cycles have better survival.

Major finding: The 5-year overall survival rate was significantly higher in patients who did vs did not complete ≥3 cycles of R-CHOP (58.5% vs 24.2%; P < .001) and in those who did vs did not achieve complete or partial response after R-CHOP (56.9% vs 14.1%; P < .001).

Study details: Findings are from a single-center real-world retrospective study including 165 patients with DLBCL who did not receive the planned 6 cycles of R-CHOP.

Disclosures: No information on the source of funding was provided. SS Yoon declared serving as an advisor for and receiving research grants from various organizations.

Source: Yoon J et al. Clinical outcomes after incomplete cycles of R-CHOP for diffuse large B-cell lymphoma: 10 years' real-world experience in a single institute. Ann Hematol. 2023;102:1467-1476 (Apr 26). Doi: 10.1007/s00277-023-05179-5

Key clinical point: Among patients with diffuse large B-cell lymphoma (DLBCL) who do not complete the recommended six cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) combination chemotherapy, those who do vs do not achieve primary response or complete ≥3 chemotherapy cycles have better survival.

Major finding: The 5-year overall survival rate was significantly higher in patients who did vs did not complete ≥3 cycles of R-CHOP (58.5% vs 24.2%; P < .001) and in those who did vs did not achieve complete or partial response after R-CHOP (56.9% vs 14.1%; P < .001).

Study details: Findings are from a single-center real-world retrospective study including 165 patients with DLBCL who did not receive the planned 6 cycles of R-CHOP.

Disclosures: No information on the source of funding was provided. SS Yoon declared serving as an advisor for and receiving research grants from various organizations.

Source: Yoon J et al. Clinical outcomes after incomplete cycles of R-CHOP for diffuse large B-cell lymphoma: 10 years' real-world experience in a single institute. Ann Hematol. 2023;102:1467-1476 (Apr 26). Doi: 10.1007/s00277-023-05179-5

Key clinical point: Orelabrutinib showed considerable efficacy and a favorable safety profile in patients with relapsed or refractory mantle cell lymphoma (MCL).

Major finding: After a median follow-up of 23.8 months, the overall response rate was 81.1%, with 27.4% and 53.8% of patients achieving complete and partial responses, respectively. The median duration of response and progression-free survival were 22.9 (95% CI 16.4-not reached) and 22.0 (95% CI 13.8-not reached) months, respectively. The median overall survival was not reached. Most adverse events (AE) were grade 1 or 2. Grade ≥3 AE were infrequent, with thrombocytopenia (13.2%), neutropenia (8.5%), and anemia (7.5%) being the most common.

Study details: This multicenter phase 1/2 study included adult patients with MCL who had relapsed after or were refractory to ≥1 and ≤4 prior therapies and received 150 mg oral orelabrutinib once daily (n = 86) or 100 mg twice daily (n = 20).

Disclosures: This study was sponsored by InnoCare Pharma Limited, China. Four authors declared being employees of InnoCare. The other authors declared no financial conflicts of interest.

Source: Deng LJ et al. Orelabrutinib for the treatment of relapsed or refractory MCL: A phase 1/2, open-label, multicenter, single-arm study. Blood Adv. 2023 (Apr 20). Doi: 10.1182/bloodadvances.2022009168

Key clinical point: Orelabrutinib showed considerable efficacy and a favorable safety profile in patients with relapsed or refractory mantle cell lymphoma (MCL).

Major finding: After a median follow-up of 23.8 months, the overall response rate was 81.1%, with 27.4% and 53.8% of patients achieving complete and partial responses, respectively. The median duration of response and progression-free survival were 22.9 (95% CI 16.4-not reached) and 22.0 (95% CI 13.8-not reached) months, respectively. The median overall survival was not reached. Most adverse events (AE) were grade 1 or 2. Grade ≥3 AE were infrequent, with thrombocytopenia (13.2%), neutropenia (8.5%), and anemia (7.5%) being the most common.

Study details: This multicenter phase 1/2 study included adult patients with MCL who had relapsed after or were refractory to ≥1 and ≤4 prior therapies and received 150 mg oral orelabrutinib once daily (n = 86) or 100 mg twice daily (n = 20).

Disclosures: This study was sponsored by InnoCare Pharma Limited, China. Four authors declared being employees of InnoCare. The other authors declared no financial conflicts of interest.

Source: Deng LJ et al. Orelabrutinib for the treatment of relapsed or refractory MCL: A phase 1/2, open-label, multicenter, single-arm study. Blood Adv. 2023 (Apr 20). Doi: 10.1182/bloodadvances.2022009168

Key clinical point: Orelabrutinib showed considerable efficacy and a favorable safety profile in patients with relapsed or refractory mantle cell lymphoma (MCL).

Major finding: After a median follow-up of 23.8 months, the overall response rate was 81.1%, with 27.4% and 53.8% of patients achieving complete and partial responses, respectively. The median duration of response and progression-free survival were 22.9 (95% CI 16.4-not reached) and 22.0 (95% CI 13.8-not reached) months, respectively. The median overall survival was not reached. Most adverse events (AE) were grade 1 or 2. Grade ≥3 AE were infrequent, with thrombocytopenia (13.2%), neutropenia (8.5%), and anemia (7.5%) being the most common.

Study details: This multicenter phase 1/2 study included adult patients with MCL who had relapsed after or were refractory to ≥1 and ≤4 prior therapies and received 150 mg oral orelabrutinib once daily (n = 86) or 100 mg twice daily (n = 20).

Disclosures: This study was sponsored by InnoCare Pharma Limited, China. Four authors declared being employees of InnoCare. The other authors declared no financial conflicts of interest.

Source: Deng LJ et al. Orelabrutinib for the treatment of relapsed or refractory MCL: A phase 1/2, open-label, multicenter, single-arm study. Blood Adv. 2023 (Apr 20). Doi: 10.1182/bloodadvances.2022009168

Key clinical point: First-line autologous stem cell transplantation (ASCT) resulted in long-term clinical and molecular remissions in patients with disseminated mantle cell lymphoma (MCL).

Major finding: The 10-year overall survival, progression-free survival, and freedom from progression rates for the first-line vs second-line cohort were 64%, 52%, and 59% vs 50%, 20%, and 20%, respectively. Overall, 27 patients experienced sustained clinical remissions between 5 and 19 years, of which 26 were continuously minimal residual disease (MRD) negative based on all samples collected after ASCT.

Study details: The data come from a partly prospective and partly retrospective study including 65 patients with disseminated MCL who received high-dose therapy with ASCT as first- (n = 54), second- (n = 10), or third-line (n = 1) treatment.

Disclosures: The MRD analysis was partly funded by BMBF (The Federal Ministry of Education and Research, Germany). M Dreyling declared serving on the scientific advisory boards of and receiving research support and speaker honoraria from various organizations. Other authors declared no conflicts of interest.

Source: Metzner B et al. Long-term outcome in patients with mantle cell lymphoma following high-dose therapy and autologous stem cell transplantation. Eur J Haematol. 2023 (Apr 24). Doi: 10.1111/ejh.13985

Key clinical point: First-line autologous stem cell transplantation (ASCT) resulted in long-term clinical and molecular remissions in patients with disseminated mantle cell lymphoma (MCL).

Major finding: The 10-year overall survival, progression-free survival, and freedom from progression rates for the first-line vs second-line cohort were 64%, 52%, and 59% vs 50%, 20%, and 20%, respectively. Overall, 27 patients experienced sustained clinical remissions between 5 and 19 years, of which 26 were continuously minimal residual disease (MRD) negative based on all samples collected after ASCT.

Study details: The data come from a partly prospective and partly retrospective study including 65 patients with disseminated MCL who received high-dose therapy with ASCT as first- (n = 54), second- (n = 10), or third-line (n = 1) treatment.

Disclosures: The MRD analysis was partly funded by BMBF (The Federal Ministry of Education and Research, Germany). M Dreyling declared serving on the scientific advisory boards of and receiving research support and speaker honoraria from various organizations. Other authors declared no conflicts of interest.

Source: Metzner B et al. Long-term outcome in patients with mantle cell lymphoma following high-dose therapy and autologous stem cell transplantation. Eur J Haematol. 2023 (Apr 24). Doi: 10.1111/ejh.13985

Key clinical point: First-line autologous stem cell transplantation (ASCT) resulted in long-term clinical and molecular remissions in patients with disseminated mantle cell lymphoma (MCL).

Major finding: The 10-year overall survival, progression-free survival, and freedom from progression rates for the first-line vs second-line cohort were 64%, 52%, and 59% vs 50%, 20%, and 20%, respectively. Overall, 27 patients experienced sustained clinical remissions between 5 and 19 years, of which 26 were continuously minimal residual disease (MRD) negative based on all samples collected after ASCT.

Study details: The data come from a partly prospective and partly retrospective study including 65 patients with disseminated MCL who received high-dose therapy with ASCT as first- (n = 54), second- (n = 10), or third-line (n = 1) treatment.

Disclosures: The MRD analysis was partly funded by BMBF (The Federal Ministry of Education and Research, Germany). M Dreyling declared serving on the scientific advisory boards of and receiving research support and speaker honoraria from various organizations. Other authors declared no conflicts of interest.

Source: Metzner B et al. Long-term outcome in patients with mantle cell lymphoma following high-dose therapy and autologous stem cell transplantation. Eur J Haematol. 2023 (Apr 24). Doi: 10.1111/ejh.13985

Key clinical point: Single nucleotide polymorphisms (SNP) of genes encoding specific cellular proteins may be associated with clinical outcomes and represent predictive biomarkers of poor response to lenalidomide maintenance after autologous stem cell transplantation (ASCT) in mantle cell lymphoma (MCL).

Major finding: Patients with ABCB1 or VEGF polymorphisms vs homozygous wild type (WT) in the lenalidomide arm had significantly higher 3-year progression-free survival (PFS) rates (85% vs 70%; P  =  .047 and 85% vs 60%; P  =  .0021, respectively). Lenalidomide vs observation did not improve 3-year PFS rates in patients carrying both ABCB1 and VEGF WT (P  =  .632).

Study details: This pharmacogenetic study included 278 adult patients with previously untreated MCL and adequate biological samples from the phase 3 MCL0208 study, 197 of whom were genotyped after ASCT and randomly assigned to the lenalidomide maintenance or observation arm.

Disclosures: This study was funded by Cancer Research UK and others. Some authors reported ties with various organizations.

Source: Ferrero S et al. Candidate germline biomarkers of lenalidomide efficacy in mantle cell lymphoma: The FIL MCL0208 trial. Blood Adv. 2023 (Apr 14). Doi: 10.1182/bloodadvances.2022009504

Key clinical point: Single nucleotide polymorphisms (SNP) of genes encoding specific cellular proteins may be associated with clinical outcomes and represent predictive biomarkers of poor response to lenalidomide maintenance after autologous stem cell transplantation (ASCT) in mantle cell lymphoma (MCL).

Major finding: Patients with ABCB1 or VEGF polymorphisms vs homozygous wild type (WT) in the lenalidomide arm had significantly higher 3-year progression-free survival (PFS) rates (85% vs 70%; P  =  .047 and 85% vs 60%; P  =  .0021, respectively). Lenalidomide vs observation did not improve 3-year PFS rates in patients carrying both ABCB1 and VEGF WT (P  =  .632).

Study details: This pharmacogenetic study included 278 adult patients with previously untreated MCL and adequate biological samples from the phase 3 MCL0208 study, 197 of whom were genotyped after ASCT and randomly assigned to the lenalidomide maintenance or observation arm.

Disclosures: This study was funded by Cancer Research UK and others. Some authors reported ties with various organizations.

Source: Ferrero S et al. Candidate germline biomarkers of lenalidomide efficacy in mantle cell lymphoma: The FIL MCL0208 trial. Blood Adv. 2023 (Apr 14). Doi: 10.1182/bloodadvances.2022009504

Key clinical point: Single nucleotide polymorphisms (SNP) of genes encoding specific cellular proteins may be associated with clinical outcomes and represent predictive biomarkers of poor response to lenalidomide maintenance after autologous stem cell transplantation (ASCT) in mantle cell lymphoma (MCL).

Major finding: Patients with ABCB1 or VEGF polymorphisms vs homozygous wild type (WT) in the lenalidomide arm had significantly higher 3-year progression-free survival (PFS) rates (85% vs 70%; P  =  .047 and 85% vs 60%; P  =  .0021, respectively). Lenalidomide vs observation did not improve 3-year PFS rates in patients carrying both ABCB1 and VEGF WT (P  =  .632).

Study details: This pharmacogenetic study included 278 adult patients with previously untreated MCL and adequate biological samples from the phase 3 MCL0208 study, 197 of whom were genotyped after ASCT and randomly assigned to the lenalidomide maintenance or observation arm.

Disclosures: This study was funded by Cancer Research UK and others. Some authors reported ties with various organizations.

Source: Ferrero S et al. Candidate germline biomarkers of lenalidomide efficacy in mantle cell lymphoma: The FIL MCL0208 trial. Blood Adv. 2023 (Apr 14). Doi: 10.1182/bloodadvances.2022009504

Key clinical point: The addition of venetoclax to ibrutinib treatment led to a high rate of undetectable measurable residual disease with 10^–4 sensitivity (U-MRD4) in the bone marrow (BM) in high-risk patients with chronic lymphocytic leukemia (CLL).

Major finding: Adding venetoclax to ibrutinib therapy led to a cumulative BM U-MRD4 rate of 73%. BM U-MRD4 was achieved by 71% of patients after venetoclax therapy completion and by 38% and 57% of patients after 6 and 12 cycles, respectively.

Study details: This phase 2 study included 45 patients with CLL and detectable disease (≥0.01% measurable residual disease in BM) treated with ibrutinib for ≥12 months who had ≥1 high-risk feature for disease progression and received combined treatment with ibrutinib (previously tolerated dose) and venetoclax (escalated to 400 mg once daily) for ≤24 cycles.

Disclosures: This study was funded by AbbVie. Some authors declared serving as consultants or on speaker’s bureaus for or receiving advisory board or consulting honoraria or research support from AbbVie and others.

Source: Thompson PA et al. Venetoclax consolidation in high-risk CLL treated with ibrutinib for ≥1 year achieves a high rate of undetectable MRD. Leukemia. 2023 (May 3). Doi: 10.1038/s41375-023-01901-4

Key clinical point: The addition of venetoclax to ibrutinib treatment led to a high rate of undetectable measurable residual disease with 10^–4 sensitivity (U-MRD4) in the bone marrow (BM) in high-risk patients with chronic lymphocytic leukemia (CLL).

Major finding: Adding venetoclax to ibrutinib therapy led to a cumulative BM U-MRD4 rate of 73%. BM U-MRD4 was achieved by 71% of patients after venetoclax therapy completion and by 38% and 57% of patients after 6 and 12 cycles, respectively.

Study details: This phase 2 study included 45 patients with CLL and detectable disease (≥0.01% measurable residual disease in BM) treated with ibrutinib for ≥12 months who had ≥1 high-risk feature for disease progression and received combined treatment with ibrutinib (previously tolerated dose) and venetoclax (escalated to 400 mg once daily) for ≤24 cycles.

Disclosures: This study was funded by AbbVie. Some authors declared serving as consultants or on speaker’s bureaus for or receiving advisory board or consulting honoraria or research support from AbbVie and others.

Source: Thompson PA et al. Venetoclax consolidation in high-risk CLL treated with ibrutinib for ≥1 year achieves a high rate of undetectable MRD. Leukemia. 2023 (May 3). Doi: 10.1038/s41375-023-01901-4

Key clinical point: The addition of venetoclax to ibrutinib treatment led to a high rate of undetectable measurable residual disease with 10^–4 sensitivity (U-MRD4) in the bone marrow (BM) in high-risk patients with chronic lymphocytic leukemia (CLL).

Major finding: Adding venetoclax to ibrutinib therapy led to a cumulative BM U-MRD4 rate of 73%. BM U-MRD4 was achieved by 71% of patients after venetoclax therapy completion and by 38% and 57% of patients after 6 and 12 cycles, respectively.

Study details: This phase 2 study included 45 patients with CLL and detectable disease (≥0.01% measurable residual disease in BM) treated with ibrutinib for ≥12 months who had ≥1 high-risk feature for disease progression and received combined treatment with ibrutinib (previously tolerated dose) and venetoclax (escalated to 400 mg once daily) for ≤24 cycles.

Disclosures: This study was funded by AbbVie. Some authors declared serving as consultants or on speaker’s bureaus for or receiving advisory board or consulting honoraria or research support from AbbVie and others.

Source: Thompson PA et al. Venetoclax consolidation in high-risk CLL treated with ibrutinib for ≥1 year achieves a high rate of undetectable MRD. Leukemia. 2023 (May 3). Doi: 10.1038/s41375-023-01901-4