B Cell Lymphoma

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

Key clinical point: The addition of rituximab to chemotherapy increased the risk for prolonged hypogammaglobulinemia in children with high-risk mature B-cell non-Hodgkin lymphoma (B-NHL); however, severe infections after therapy completion were rare.

Major finding: At 1 year after therapy commencement, the chemotherapy+rituximab vs chemotherapy arm had a significantly higher proportion of children with low immunoglobulin G levels (55% vs 25%; odds ratio 3.64; P  =  .0003). The occurrence of grade ≥3 nonhematologic adverse events after 1 month of therapy completion was rare.

Study details: This secondary analysis of the Inter-B-NHL-Ritux 2010 trial included children (6 months-18 years) with high-risk mature B-NHL who were randomly (n = 289) or nonrandomly (n = 132) assigned to receive either chemotherapy alone or chemotherapy+rituximab.

Disclosures: The Inter-B-NHL-Ritux 2010 trial was supported by F Hoffmann-La Roche and others, and this study was funded by the National Cancer Institute of the US National Institutes of Health. Some authors reported ties with F Hoffmann-La Roche or other sources.

Source: Alexander S et al for the Children's Oncology Group and the European Intergroup for Childhood Non-Hodgkin's Lymphoma. Effect of rituximab on immune status in children with mature B-cell non-Hodgkin lymphoma: A prespecified secondary analysis of the Inter-B-NHL Ritux 2010 trial. Lancet Haematol. 2023 (Apr 21). Doi: 10.1016/S2352-3026(23)00062-5

Key clinical point: The addition of rituximab to chemotherapy increased the risk for prolonged hypogammaglobulinemia in children with high-risk mature B-cell non-Hodgkin lymphoma (B-NHL); however, severe infections after therapy completion were rare.

Major finding: At 1 year after therapy commencement, the chemotherapy+rituximab vs chemotherapy arm had a significantly higher proportion of children with low immunoglobulin G levels (55% vs 25%; odds ratio 3.64; P  =  .0003). The occurrence of grade ≥3 nonhematologic adverse events after 1 month of therapy completion was rare.

Study details: This secondary analysis of the Inter-B-NHL-Ritux 2010 trial included children (6 months-18 years) with high-risk mature B-NHL who were randomly (n = 289) or nonrandomly (n = 132) assigned to receive either chemotherapy alone or chemotherapy+rituximab.

Disclosures: The Inter-B-NHL-Ritux 2010 trial was supported by F Hoffmann-La Roche and others, and this study was funded by the National Cancer Institute of the US National Institutes of Health. Some authors reported ties with F Hoffmann-La Roche or other sources.

Source: Alexander S et al for the Children's Oncology Group and the European Intergroup for Childhood Non-Hodgkin's Lymphoma. Effect of rituximab on immune status in children with mature B-cell non-Hodgkin lymphoma: A prespecified secondary analysis of the Inter-B-NHL Ritux 2010 trial. Lancet Haematol. 2023 (Apr 21). Doi: 10.1016/S2352-3026(23)00062-5

Key clinical point: The addition of rituximab to chemotherapy increased the risk for prolonged hypogammaglobulinemia in children with high-risk mature B-cell non-Hodgkin lymphoma (B-NHL); however, severe infections after therapy completion were rare.

Major finding: At 1 year after therapy commencement, the chemotherapy+rituximab vs chemotherapy arm had a significantly higher proportion of children with low immunoglobulin G levels (55% vs 25%; odds ratio 3.64; P  =  .0003). The occurrence of grade ≥3 nonhematologic adverse events after 1 month of therapy completion was rare.

Study details: This secondary analysis of the Inter-B-NHL-Ritux 2010 trial included children (6 months-18 years) with high-risk mature B-NHL who were randomly (n = 289) or nonrandomly (n = 132) assigned to receive either chemotherapy alone or chemotherapy+rituximab.

Disclosures: The Inter-B-NHL-Ritux 2010 trial was supported by F Hoffmann-La Roche and others, and this study was funded by the National Cancer Institute of the US National Institutes of Health. Some authors reported ties with F Hoffmann-La Roche or other sources.

Source: Alexander S et al for the Children's Oncology Group and the European Intergroup for Childhood Non-Hodgkin's Lymphoma. Effect of rituximab on immune status in children with mature B-cell non-Hodgkin lymphoma: A prespecified secondary analysis of the Inter-B-NHL Ritux 2010 trial. Lancet Haematol. 2023 (Apr 21). Doi: 10.1016/S2352-3026(23)00062-5

Key clinical point: Compared with the standard intravenous (IV) rituximab induction therapy, a short subcutaneous rituximab maintenance therapy after subcutaneous rituximab induction therapy improves complete response (CR) and progression-free survival (PFS) in patients with CD20⁺ low-tumor burden follicular lymphoma (FL).

Major finding: Patients receiving rituximab induction (first IV and then subcutaneous) followed by a short subcutaneous rituximab maintenance therapy (four infusions; experimental arm) vs four weekly IV rituximab infusions (control arm) had significantly higher 4-year PFS (58.1% vs 41.2%; hazard ratio 0.585; P  =  .008) and CR (59.0% vs 36.3%; P  =  .001) rates.

Study details: Findings are from a phase 3 study, FLIRT, that included 202 patients with CD20⁺ low-tumor burden FL who were randomly assigned to the control or experimental arm.

Disclosures: This study was supported by the Lymphoma Academic Research Organization (LYSARC), France. Some authors declared serving as consultants or advisors for or receiving honoraria, research funding, or travel and accommodation expenses from various sources.

Source: Cartron G et al. Randomized phase III trial evaluating subcutaneous rituximab for the first-line treatment of low–tumor burden follicular lymphoma: Results of a LYSA study. J Clin Oncol. 2023 (Apr 18). Doi: 10.1200/JCO.22.02327

Key clinical point: Compared with the standard intravenous (IV) rituximab induction therapy, a short subcutaneous rituximab maintenance therapy after subcutaneous rituximab induction therapy improves complete response (CR) and progression-free survival (PFS) in patients with CD20⁺ low-tumor burden follicular lymphoma (FL).

Major finding: Patients receiving rituximab induction (first IV and then subcutaneous) followed by a short subcutaneous rituximab maintenance therapy (four infusions; experimental arm) vs four weekly IV rituximab infusions (control arm) had significantly higher 4-year PFS (58.1% vs 41.2%; hazard ratio 0.585; P  =  .008) and CR (59.0% vs 36.3%; P  =  .001) rates.

Study details: Findings are from a phase 3 study, FLIRT, that included 202 patients with CD20⁺ low-tumor burden FL who were randomly assigned to the control or experimental arm.

Disclosures: This study was supported by the Lymphoma Academic Research Organization (LYSARC), France. Some authors declared serving as consultants or advisors for or receiving honoraria, research funding, or travel and accommodation expenses from various sources.

Source: Cartron G et al. Randomized phase III trial evaluating subcutaneous rituximab for the first-line treatment of low–tumor burden follicular lymphoma: Results of a LYSA study. J Clin Oncol. 2023 (Apr 18). Doi: 10.1200/JCO.22.02327

Key clinical point: Compared with the standard intravenous (IV) rituximab induction therapy, a short subcutaneous rituximab maintenance therapy after subcutaneous rituximab induction therapy improves complete response (CR) and progression-free survival (PFS) in patients with CD20⁺ low-tumor burden follicular lymphoma (FL).

Major finding: Patients receiving rituximab induction (first IV and then subcutaneous) followed by a short subcutaneous rituximab maintenance therapy (four infusions; experimental arm) vs four weekly IV rituximab infusions (control arm) had significantly higher 4-year PFS (58.1% vs 41.2%; hazard ratio 0.585; P  =  .008) and CR (59.0% vs 36.3%; P  =  .001) rates.

Study details: Findings are from a phase 3 study, FLIRT, that included 202 patients with CD20⁺ low-tumor burden FL who were randomly assigned to the control or experimental arm.

Disclosures: This study was supported by the Lymphoma Academic Research Organization (LYSARC), France. Some authors declared serving as consultants or advisors for or receiving honoraria, research funding, or travel and accommodation expenses from various sources.

Source: Cartron G et al. Randomized phase III trial evaluating subcutaneous rituximab for the first-line treatment of low–tumor burden follicular lymphoma: Results of a LYSA study. J Clin Oncol. 2023 (Apr 18). Doi: 10.1200/JCO.22.02327

Key clinical point: Compared with fludarabine, cyclophosphamide, and rituximab, ibrutinib and rituximab provided a significant progression-free survival (PFS) benefit in treatment-naive patients with chronic lymphocytic leukemia (CLL).

Major finding: After a median follow-up of 53 months, the median PFS was not reached in patients receiving ibrutinib and rituximab and was 67 months (95% CI 63-not reached) in those receiving fludarabine, cyclophosphamide, and rituximab (hazard ratio 0.44; P < .0001). A substantial number of sudden cardiac or unexplained deaths occurred, which were more frequent in the ibrutinib and rituximab group.

Study details: This interim analysis of the multicenter phase 3 FLAIR trial included 771 treatment-naive adult patients with CLL or small lymphocytic lymphoma who were randomly assigned to receive ibrutinib and rituximab (n = 386) or fludarabine, cyclophosphamide, and rituximab (n = 385).

Disclosures: This study was funded by Cancer Research UK, Janssen, and others. Some authors declared participating on data safety monitoring or advisory boards and receiving grants, personal consulting or speaker fees, lecture honoraria, or travel support from the study funders and others.

Source: Hillmen P et al. Ibrutinib and rituximab versus fludarabine, cyclophosphamide, and rituximab for patients with previously untreated chronic lymphocytic leukaemia (FLAIR): Interim analysis of a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2023;24(5):535-552 (May). Doi: 10.1016/S1470-2045(23)00144-4

Key clinical point: Compared with fludarabine, cyclophosphamide, and rituximab, ibrutinib and rituximab provided a significant progression-free survival (PFS) benefit in treatment-naive patients with chronic lymphocytic leukemia (CLL).

Major finding: After a median follow-up of 53 months, the median PFS was not reached in patients receiving ibrutinib and rituximab and was 67 months (95% CI 63-not reached) in those receiving fludarabine, cyclophosphamide, and rituximab (hazard ratio 0.44; P < .0001). A substantial number of sudden cardiac or unexplained deaths occurred, which were more frequent in the ibrutinib and rituximab group.

Study details: This interim analysis of the multicenter phase 3 FLAIR trial included 771 treatment-naive adult patients with CLL or small lymphocytic lymphoma who were randomly assigned to receive ibrutinib and rituximab (n = 386) or fludarabine, cyclophosphamide, and rituximab (n = 385).

Disclosures: This study was funded by Cancer Research UK, Janssen, and others. Some authors declared participating on data safety monitoring or advisory boards and receiving grants, personal consulting or speaker fees, lecture honoraria, or travel support from the study funders and others.

Source: Hillmen P et al. Ibrutinib and rituximab versus fludarabine, cyclophosphamide, and rituximab for patients with previously untreated chronic lymphocytic leukaemia (FLAIR): Interim analysis of a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2023;24(5):535-552 (May). Doi: 10.1016/S1470-2045(23)00144-4

Key clinical point: Compared with fludarabine, cyclophosphamide, and rituximab, ibrutinib and rituximab provided a significant progression-free survival (PFS) benefit in treatment-naive patients with chronic lymphocytic leukemia (CLL).

Major finding: After a median follow-up of 53 months, the median PFS was not reached in patients receiving ibrutinib and rituximab and was 67 months (95% CI 63-not reached) in those receiving fludarabine, cyclophosphamide, and rituximab (hazard ratio 0.44; P < .0001). A substantial number of sudden cardiac or unexplained deaths occurred, which were more frequent in the ibrutinib and rituximab group.

Study details: This interim analysis of the multicenter phase 3 FLAIR trial included 771 treatment-naive adult patients with CLL or small lymphocytic lymphoma who were randomly assigned to receive ibrutinib and rituximab (n = 386) or fludarabine, cyclophosphamide, and rituximab (n = 385).

Disclosures: This study was funded by Cancer Research UK, Janssen, and others. Some authors declared participating on data safety monitoring or advisory boards and receiving grants, personal consulting or speaker fees, lecture honoraria, or travel support from the study funders and others.

Source: Hillmen P et al. Ibrutinib and rituximab versus fludarabine, cyclophosphamide, and rituximab for patients with previously untreated chronic lymphocytic leukaemia (FLAIR): Interim analysis of a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2023;24(5):535-552 (May). Doi: 10.1016/S1470-2045(23)00144-4