B-Cell Lymphoma ICYMI

Key clinical point: The ibrutinib + bortezomib combination shows durable efficacy and manageable safety in patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL), including high-risk patients.

Major finding: The combination led to an objective response rate of 81.8% (90% CI 71.1%-89.8%), which increased to 87.3% (90% CI 77.4%-93.9%) with ibrutinib maintenance. At a 25.4-month median follow-up, the median duration of response and progression-free survival were 22.7 (95% CI 12.3-not achieved) and 18.6 (95% CI 12.5-not achieved) months, respectively. The adverse event profile was consistent with the known safety profiles of individual drugs.

Study details: This phase 2 trial included 55 ibrutinib-naive and bortezomib-naive patients with R/R MCL previously treated with ≤2 lines of chemotherapy (of whom 75.6% had ≥1 high-risk features) who received 6 cycles of ibrutinib + bortezomib followed by ibrutinib maintenance.

Disclosures: This study was supported by Janssen and others. Some authors declared serving on the advisory boards of or receiving research funding, consulting fees, honoraria, or meeting or travel support from various sources, including Janssen.

Source: Novak U et al. Combined therapy with ibrutinib and bortezomib followed by ibrutinib maintenance in relapsed or refractory mantle cell lymphoma and high-risk features: A phase 1/2 trial of the European MCL network (SAKK 36/13). EClinicalMedicine. 2023;64:102221 (Sep 21). doi: 10.1016/j.eclinm.2023.102221

Key clinical point: The ibrutinib + bortezomib combination shows durable efficacy and manageable safety in patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL), including high-risk patients.

Major finding: The combination led to an objective response rate of 81.8% (90% CI 71.1%-89.8%), which increased to 87.3% (90% CI 77.4%-93.9%) with ibrutinib maintenance. At a 25.4-month median follow-up, the median duration of response and progression-free survival were 22.7 (95% CI 12.3-not achieved) and 18.6 (95% CI 12.5-not achieved) months, respectively. The adverse event profile was consistent with the known safety profiles of individual drugs.

Study details: This phase 2 trial included 55 ibrutinib-naive and bortezomib-naive patients with R/R MCL previously treated with ≤2 lines of chemotherapy (of whom 75.6% had ≥1 high-risk features) who received 6 cycles of ibrutinib + bortezomib followed by ibrutinib maintenance.

Disclosures: This study was supported by Janssen and others. Some authors declared serving on the advisory boards of or receiving research funding, consulting fees, honoraria, or meeting or travel support from various sources, including Janssen.

Source: Novak U et al. Combined therapy with ibrutinib and bortezomib followed by ibrutinib maintenance in relapsed or refractory mantle cell lymphoma and high-risk features: A phase 1/2 trial of the European MCL network (SAKK 36/13). EClinicalMedicine. 2023;64:102221 (Sep 21). doi: 10.1016/j.eclinm.2023.102221

Key clinical point: The ibrutinib + bortezomib combination shows durable efficacy and manageable safety in patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL), including high-risk patients.

Major finding: The combination led to an objective response rate of 81.8% (90% CI 71.1%-89.8%), which increased to 87.3% (90% CI 77.4%-93.9%) with ibrutinib maintenance. At a 25.4-month median follow-up, the median duration of response and progression-free survival were 22.7 (95% CI 12.3-not achieved) and 18.6 (95% CI 12.5-not achieved) months, respectively. The adverse event profile was consistent with the known safety profiles of individual drugs.

Study details: This phase 2 trial included 55 ibrutinib-naive and bortezomib-naive patients with R/R MCL previously treated with ≤2 lines of chemotherapy (of whom 75.6% had ≥1 high-risk features) who received 6 cycles of ibrutinib + bortezomib followed by ibrutinib maintenance.

Disclosures: This study was supported by Janssen and others. Some authors declared serving on the advisory boards of or receiving research funding, consulting fees, honoraria, or meeting or travel support from various sources, including Janssen.

Source: Novak U et al. Combined therapy with ibrutinib and bortezomib followed by ibrutinib maintenance in relapsed or refractory mantle cell lymphoma and high-risk features: A phase 1/2 trial of the European MCL network (SAKK 36/13). EClinicalMedicine. 2023;64:102221 (Sep 21). doi: 10.1016/j.eclinm.2023.102221

Key clinical point: Ibrutinib maintenance (I-M; dose 560 mg daily) for 4 years is effective in patients with treatment-naive mantle cell lymphoma (MCL) who are responsive to frontline chemo-immunotherapy with significant but manageable toxicities.

Major finding: The 3-year progression-free survival (PFS) and overall survival (OS) rates were 94% and 97%, whereas the 5-year PFS and OS rates were 89% and 91%, respectively. In patients with prior autologous stem cell transplantation (autoSCT), the 5-year PFS and OS rates were 100% each. The most common treatment-related adverse event was infection (86%; grades 1-2), and the most common grade 3-4 toxicities were hematologic.

Study details: This multicenter phase 2 study included patients with treatment-naive MCL who achieved a complete or partial response to frontline intensive induction chemo-immunotherapy with or without autoSCT and received 560 mg I-M daily for 4 years.

Disclosures: This study was supported by Pharmacyclics and Janssen. R Karmali and B Pro declared serving as consultants, speakers, or advisory board members for or receiving research funding or honoraria from various sources.

Source: Karmali R et al. Ibrutinib maintenance following frontline treatment in patients with mantle cell lymphoma. Blood Adv. 2023 (Sep 27). doi: 10.1182/bloodadvances.2023011271

Key clinical point: Ibrutinib maintenance (I-M; dose 560 mg daily) for 4 years is effective in patients with treatment-naive mantle cell lymphoma (MCL) who are responsive to frontline chemo-immunotherapy with significant but manageable toxicities.

Major finding: The 3-year progression-free survival (PFS) and overall survival (OS) rates were 94% and 97%, whereas the 5-year PFS and OS rates were 89% and 91%, respectively. In patients with prior autologous stem cell transplantation (autoSCT), the 5-year PFS and OS rates were 100% each. The most common treatment-related adverse event was infection (86%; grades 1-2), and the most common grade 3-4 toxicities were hematologic.

Study details: This multicenter phase 2 study included patients with treatment-naive MCL who achieved a complete or partial response to frontline intensive induction chemo-immunotherapy with or without autoSCT and received 560 mg I-M daily for 4 years.

Disclosures: This study was supported by Pharmacyclics and Janssen. R Karmali and B Pro declared serving as consultants, speakers, or advisory board members for or receiving research funding or honoraria from various sources.

Source: Karmali R et al. Ibrutinib maintenance following frontline treatment in patients with mantle cell lymphoma. Blood Adv. 2023 (Sep 27). doi: 10.1182/bloodadvances.2023011271

Key clinical point: Ibrutinib maintenance (I-M; dose 560 mg daily) for 4 years is effective in patients with treatment-naive mantle cell lymphoma (MCL) who are responsive to frontline chemo-immunotherapy with significant but manageable toxicities.

Major finding: The 3-year progression-free survival (PFS) and overall survival (OS) rates were 94% and 97%, whereas the 5-year PFS and OS rates were 89% and 91%, respectively. In patients with prior autologous stem cell transplantation (autoSCT), the 5-year PFS and OS rates were 100% each. The most common treatment-related adverse event was infection (86%; grades 1-2), and the most common grade 3-4 toxicities were hematologic.

Study details: This multicenter phase 2 study included patients with treatment-naive MCL who achieved a complete or partial response to frontline intensive induction chemo-immunotherapy with or without autoSCT and received 560 mg I-M daily for 4 years.

Disclosures: This study was supported by Pharmacyclics and Janssen. R Karmali and B Pro declared serving as consultants, speakers, or advisory board members for or receiving research funding or honoraria from various sources.

Source: Karmali R et al. Ibrutinib maintenance following frontline treatment in patients with mantle cell lymphoma. Blood Adv. 2023 (Sep 27). doi: 10.1182/bloodadvances.2023011271

Key clinical point: Prophylaxis with high-dose methotrexate (HD-MTX) was not associated with a clinically meaningful reduction in the risk for central nervous system (CNS) progression in high-risk patients with aggressive B-cell lymphoma (BCL).

Major finding: Patients who did vs did not receive HD-MTX had a significantly lower risk for CNS progression (adjusted 5-year risk difference 1.6%; adjusted hazard ratio [aHR] 0.59; P = .014), but the significance was lost when considering only those who achieved a complete response at chemoimmunotherapy completion (adjusted 5-year risk difference 1.4%; aHR 0.74; P = .30).

Study details: This multicenter retrospective study included 2418 adults with aggressive BCL and a high risk for CNS progression treated with curative-intent anti-CD20-based chemoimmunotherapy who did or did not receive HD-MTX, of whom 1616 achieved a complete response.

Disclosures: This study was funded by Janssen Pharmaceuticals and others. All authors except TC El-Galaly declared serving as consultants, advisors, or speakers for or receiving honoraria, research funding, or travel support from various sources, including Janssen.

Source: Lewis KL et al on behalf of the International CNS Prophylaxis Study Group. High-dose methotrexate as CNS prophylaxis in high-risk aggressive B-cell lymphoma. J Clin Oncol. 2023 (Oct 5). doi: 10.1200/JCO.23.00365

Key clinical point: Prophylaxis with high-dose methotrexate (HD-MTX) was not associated with a clinically meaningful reduction in the risk for central nervous system (CNS) progression in high-risk patients with aggressive B-cell lymphoma (BCL).

Major finding: Patients who did vs did not receive HD-MTX had a significantly lower risk for CNS progression (adjusted 5-year risk difference 1.6%; adjusted hazard ratio [aHR] 0.59; P = .014), but the significance was lost when considering only those who achieved a complete response at chemoimmunotherapy completion (adjusted 5-year risk difference 1.4%; aHR 0.74; P = .30).

Study details: This multicenter retrospective study included 2418 adults with aggressive BCL and a high risk for CNS progression treated with curative-intent anti-CD20-based chemoimmunotherapy who did or did not receive HD-MTX, of whom 1616 achieved a complete response.

Disclosures: This study was funded by Janssen Pharmaceuticals and others. All authors except TC El-Galaly declared serving as consultants, advisors, or speakers for or receiving honoraria, research funding, or travel support from various sources, including Janssen.

Source: Lewis KL et al on behalf of the International CNS Prophylaxis Study Group. High-dose methotrexate as CNS prophylaxis in high-risk aggressive B-cell lymphoma. J Clin Oncol. 2023 (Oct 5). doi: 10.1200/JCO.23.00365

Key clinical point: Prophylaxis with high-dose methotrexate (HD-MTX) was not associated with a clinically meaningful reduction in the risk for central nervous system (CNS) progression in high-risk patients with aggressive B-cell lymphoma (BCL).

Major finding: Patients who did vs did not receive HD-MTX had a significantly lower risk for CNS progression (adjusted 5-year risk difference 1.6%; adjusted hazard ratio [aHR] 0.59; P = .014), but the significance was lost when considering only those who achieved a complete response at chemoimmunotherapy completion (adjusted 5-year risk difference 1.4%; aHR 0.74; P = .30).

Study details: This multicenter retrospective study included 2418 adults with aggressive BCL and a high risk for CNS progression treated with curative-intent anti-CD20-based chemoimmunotherapy who did or did not receive HD-MTX, of whom 1616 achieved a complete response.

Disclosures: This study was funded by Janssen Pharmaceuticals and others. All authors except TC El-Galaly declared serving as consultants, advisors, or speakers for or receiving honoraria, research funding, or travel support from various sources, including Janssen.

Source: Lewis KL et al on behalf of the International CNS Prophylaxis Study Group. High-dose methotrexate as CNS prophylaxis in high-risk aggressive B-cell lymphoma. J Clin Oncol. 2023 (Oct 5). doi: 10.1200/JCO.23.00365

Key clinical point: Second-line vs later-line zanubrutinib treatment leads to significantly improved long-term survival outcomes in patients with relapsed or refractory mantle cell lymphoma (MCL).

Major finding: At a median follow-up of 35.2 months, patients receiving second-line vs later-line zanubrutinib had significantly improved median overall survival (adjusted hazard ratio 0.459; P = .044) and numerically longer median progression-free survival (27.8 vs 22.1 months). Adverse events observed in both groups were consistent with the known safety profile of zanubrutinib.

Study details: Findings are from an updated pooled analysis of 112 patients from the BGB-3111-AU-003 and BGB-3111-206 clinical trials who had relapsed or refractory MCL and received second-line (n = 41) or later-line (n = 71) zanubrutinib.

Disclosures: The BGB-3111-AU-003 and BGB-3111-206 trials were sponsored by BeiGene. C Fang and S Sun declared being employees of BeiGene Co., Ltd., China. The other authors declared no conflicts of interest.

Source: Song Y et al. Long-term outcomes of second-line versus later-line zanubrutinib treatment in patients with relapsed/refractory mantle cell lymphoma: An updated pooled analysis. Cancer Med. 2023;12(18):18643-18653 (Sep 14). doi: 10.1002/cam4.6473

Key clinical point: Second-line vs later-line zanubrutinib treatment leads to significantly improved long-term survival outcomes in patients with relapsed or refractory mantle cell lymphoma (MCL).

Major finding: At a median follow-up of 35.2 months, patients receiving second-line vs later-line zanubrutinib had significantly improved median overall survival (adjusted hazard ratio 0.459; P = .044) and numerically longer median progression-free survival (27.8 vs 22.1 months). Adverse events observed in both groups were consistent with the known safety profile of zanubrutinib.

Study details: Findings are from an updated pooled analysis of 112 patients from the BGB-3111-AU-003 and BGB-3111-206 clinical trials who had relapsed or refractory MCL and received second-line (n = 41) or later-line (n = 71) zanubrutinib.

Disclosures: The BGB-3111-AU-003 and BGB-3111-206 trials were sponsored by BeiGene. C Fang and S Sun declared being employees of BeiGene Co., Ltd., China. The other authors declared no conflicts of interest.

Source: Song Y et al. Long-term outcomes of second-line versus later-line zanubrutinib treatment in patients with relapsed/refractory mantle cell lymphoma: An updated pooled analysis. Cancer Med. 2023;12(18):18643-18653 (Sep 14). doi: 10.1002/cam4.6473

Key clinical point: Second-line vs later-line zanubrutinib treatment leads to significantly improved long-term survival outcomes in patients with relapsed or refractory mantle cell lymphoma (MCL).

Major finding: At a median follow-up of 35.2 months, patients receiving second-line vs later-line zanubrutinib had significantly improved median overall survival (adjusted hazard ratio 0.459; P = .044) and numerically longer median progression-free survival (27.8 vs 22.1 months). Adverse events observed in both groups were consistent with the known safety profile of zanubrutinib.

Study details: Findings are from an updated pooled analysis of 112 patients from the BGB-3111-AU-003 and BGB-3111-206 clinical trials who had relapsed or refractory MCL and received second-line (n = 41) or later-line (n = 71) zanubrutinib.

Disclosures: The BGB-3111-AU-003 and BGB-3111-206 trials were sponsored by BeiGene. C Fang and S Sun declared being employees of BeiGene Co., Ltd., China. The other authors declared no conflicts of interest.

Source: Song Y et al. Long-term outcomes of second-line versus later-line zanubrutinib treatment in patients with relapsed/refractory mantle cell lymphoma: An updated pooled analysis. Cancer Med. 2023;12(18):18643-18653 (Sep 14). doi: 10.1002/cam4.6473

Key clinical point: Second-line axicabtagene ciloleucel (axi-cel) provides high response rates and manageable safety in patients with high-risk relapsed or refractory (R/R) large B-cell lymphoma (LBCL) who are ineligible for autologous stem-cell transplantation (ASCT).

Major finding: At 3 months from axi-cel infusion, the complete metabolic response rate was 71.0% (95% CI 58.1%-81.8%). At a 12-month median follow-up, the median progression-free survival was 11.8 months (95% CI 8.4-not reached) whereas median overall survival was not reached. Grade ≥3 cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome occurred in 8.1% and 14.5% of patients, respectively.

Study details: Findings are from the phase 2 ALYCANTE trial including 62 ASCT-ineligible patients with high-risk R/R LBCL who underwent leukapheresis and subsequently received second-line axi-cel.

Disclosures: This study was funded by Kite, a Gilead company. Some authors declared serving as members of directors’ boards or advisory committees of or receiving honoraria, research funding, consulting fees, or travel or accommodation expenses from various sources, including Kite and Gilead.

Source: Houot R et al. Axicabtagene ciloleucel as second-line therapy in large B cell lymphoma ineligible for autologous stem cell transplantation: A phase 2 trial. Nat Med. 2023;29:2593-2601 (Sep 14). doi: 10.1038/s41591-023-02572-5

Key clinical point: Second-line axicabtagene ciloleucel (axi-cel) provides high response rates and manageable safety in patients with high-risk relapsed or refractory (R/R) large B-cell lymphoma (LBCL) who are ineligible for autologous stem-cell transplantation (ASCT).

Major finding: At 3 months from axi-cel infusion, the complete metabolic response rate was 71.0% (95% CI 58.1%-81.8%). At a 12-month median follow-up, the median progression-free survival was 11.8 months (95% CI 8.4-not reached) whereas median overall survival was not reached. Grade ≥3 cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome occurred in 8.1% and 14.5% of patients, respectively.

Study details: Findings are from the phase 2 ALYCANTE trial including 62 ASCT-ineligible patients with high-risk R/R LBCL who underwent leukapheresis and subsequently received second-line axi-cel.

Disclosures: This study was funded by Kite, a Gilead company. Some authors declared serving as members of directors’ boards or advisory committees of or receiving honoraria, research funding, consulting fees, or travel or accommodation expenses from various sources, including Kite and Gilead.

Source: Houot R et al. Axicabtagene ciloleucel as second-line therapy in large B cell lymphoma ineligible for autologous stem cell transplantation: A phase 2 trial. Nat Med. 2023;29:2593-2601 (Sep 14). doi: 10.1038/s41591-023-02572-5

Key clinical point: Second-line axicabtagene ciloleucel (axi-cel) provides high response rates and manageable safety in patients with high-risk relapsed or refractory (R/R) large B-cell lymphoma (LBCL) who are ineligible for autologous stem-cell transplantation (ASCT).

Major finding: At 3 months from axi-cel infusion, the complete metabolic response rate was 71.0% (95% CI 58.1%-81.8%). At a 12-month median follow-up, the median progression-free survival was 11.8 months (95% CI 8.4-not reached) whereas median overall survival was not reached. Grade ≥3 cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome occurred in 8.1% and 14.5% of patients, respectively.

Study details: Findings are from the phase 2 ALYCANTE trial including 62 ASCT-ineligible patients with high-risk R/R LBCL who underwent leukapheresis and subsequently received second-line axi-cel.

Disclosures: This study was funded by Kite, a Gilead company. Some authors declared serving as members of directors’ boards or advisory committees of or receiving honoraria, research funding, consulting fees, or travel or accommodation expenses from various sources, including Kite and Gilead.

Source: Houot R et al. Axicabtagene ciloleucel as second-line therapy in large B cell lymphoma ineligible for autologous stem cell transplantation: A phase 2 trial. Nat Med. 2023;29:2593-2601 (Sep 14). doi: 10.1038/s41591-023-02572-5

There have been several recent developments in the treatment of B-cell lymphoma; however, one of the most significant advances has been the development of chimeric antigen receptor (CAR) T-cell therapy. CAR T-cell therapy is a type of personalized immunotherapy that can help cure some people with aggressive non-Hodgkin lymphoma (NHL), including diffuse large B-cell lymphoma (DLBCL), the most common form of aggressive NHL. CAR T-cell therapy has revolutionized the treatment of hematologic malignancies over the past 5 years, with impressive response rates and durable remissions for patients who previously had no viable options. This strategy is highly effective in patients with relapsed/refractory DLBCL, as well as mantle cell lymphoma, follicular lymphoma, acute lymphoblastic leukemia (ALL), and multiple myeloma, as evidenced by recent regulatory approvals. 

The initial products, axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel)— both FDA approved in 2017—involve administration of autologous T-cells programmed to express a CAR targeting the B-cell marker CD19. 

In 2021, the FDA also approved lisocabtagene maraleucel (liso-cel), a new CAR T-cell therapy for the treatment of adults with relapsed or refractory (nonresponsive) large B-cell lymphoma (LBCL) have been treated with at least 2 prior lines of therapy. These products have design differences, including differences in the costimulatory domain, mechanism of gene/transgene delivery, ability for cryopreservation, and need for T-cell selection.

The CAR T-cell therapy axi-cel demonstrated superior results in the ZUMA-7 clinical trial, which compared CAR T-cell therapy directly to traditional chemotherapy with intended autologous stem cell transplant (ASCT). About 55% of patients were still alive 4 years after receiving axi-cel, compared with 46% of those who initially received the standard treatment for relapsed disease. Based on these results, axi-cel is now the preferred treatment for people whose DLBCL has recurred with 12 months of front-line treatment or who are resistant to standard initial treatment.

Additionally, the BELINDA trial was a randomized phase 3 trial that compared CAR T-cell therapy with liso-cel with second-line chemotherapy with planned ASCT. Like ZUMA-7, this study also demonstrated an improvement in progression-free survival (PFS) compared to standard treatment. As such, CAR T-cell therapy represents the new standard of care for second-line treatment in appropriate patients with refractory or early relapsing LBCL.

There have been several other recent studies on the use of CAR T-cell therapy for B-cell lymphoma. One study, published in Blood Advances (2023), found that receiving a greater number of therapies prior to CAR T-cell therapy is associated with poorer outcomes in patients with aggressive relapsed/refractory B-cell NHL. The study, which included 514 patients from 13 centers treated with CAR-T for aggressive B-cell NHL between 2015 and 2021, found that a greater number of lines of therapy before CAR-T apheresis and bridging therapy were predictive of inferior PFS and overall survival. 

Another study compared 2 CD19-targeting CAR T-cell treatments, axi-cel and tisa-cel, with ASCT in the second line setting for LBCL. The study found that axi-cel was superior to ASCT, with longer median event-free survival and a higher response rate. However, tisa-cel was not found to be superior to ASCT. Further studies will be needed to definitively characterize the relative benefits of CAR-T cell therapies and standard second-line treatments for different subgroups of patients with LBCL. 

An increasing number of effective targeted agents for DLBCL, including novel monoclonal antibodies (tafasitamab) and antibody-drug conjugates (polatuzumab vedotin and loncastuximab teserine), are being used in earlier lines of therapy. Additionally, 2 anti-CD20 bispecific antibodies (epcoritamab and glofitamab) have gained approval for relapsed/refractory DLBCL due to high response rates. Future studies will be needed to determine if treatment with these agents can produce durable remissions like that of CAR-T cell therapy.

There have been several recent developments in the treatment of B-cell lymphoma; however, one of the most significant advances has been the development of chimeric antigen receptor (CAR) T-cell therapy. CAR T-cell therapy is a type of personalized immunotherapy that can help cure some people with aggressive non-Hodgkin lymphoma (NHL), including diffuse large B-cell lymphoma (DLBCL), the most common form of aggressive NHL. CAR T-cell therapy has revolutionized the treatment of hematologic malignancies over the past 5 years, with impressive response rates and durable remissions for patients who previously had no viable options. This strategy is highly effective in patients with relapsed/refractory DLBCL, as well as mantle cell lymphoma, follicular lymphoma, acute lymphoblastic leukemia (ALL), and multiple myeloma, as evidenced by recent regulatory approvals. 

The initial products, axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel)— both FDA approved in 2017—involve administration of autologous T-cells programmed to express a CAR targeting the B-cell marker CD19. 

In 2021, the FDA also approved lisocabtagene maraleucel (liso-cel), a new CAR T-cell therapy for the treatment of adults with relapsed or refractory (nonresponsive) large B-cell lymphoma (LBCL) have been treated with at least 2 prior lines of therapy. These products have design differences, including differences in the costimulatory domain, mechanism of gene/transgene delivery, ability for cryopreservation, and need for T-cell selection.

The CAR T-cell therapy axi-cel demonstrated superior results in the ZUMA-7 clinical trial, which compared CAR T-cell therapy directly to traditional chemotherapy with intended autologous stem cell transplant (ASCT). About 55% of patients were still alive 4 years after receiving axi-cel, compared with 46% of those who initially received the standard treatment for relapsed disease. Based on these results, axi-cel is now the preferred treatment for people whose DLBCL has recurred with 12 months of front-line treatment or who are resistant to standard initial treatment.

Additionally, the BELINDA trial was a randomized phase 3 trial that compared CAR T-cell therapy with liso-cel with second-line chemotherapy with planned ASCT. Like ZUMA-7, this study also demonstrated an improvement in progression-free survival (PFS) compared to standard treatment. As such, CAR T-cell therapy represents the new standard of care for second-line treatment in appropriate patients with refractory or early relapsing LBCL.

There have been several other recent studies on the use of CAR T-cell therapy for B-cell lymphoma. One study, published in Blood Advances (2023), found that receiving a greater number of therapies prior to CAR T-cell therapy is associated with poorer outcomes in patients with aggressive relapsed/refractory B-cell NHL. The study, which included 514 patients from 13 centers treated with CAR-T for aggressive B-cell NHL between 2015 and 2021, found that a greater number of lines of therapy before CAR-T apheresis and bridging therapy were predictive of inferior PFS and overall survival. 

Another study compared 2 CD19-targeting CAR T-cell treatments, axi-cel and tisa-cel, with ASCT in the second line setting for LBCL. The study found that axi-cel was superior to ASCT, with longer median event-free survival and a higher response rate. However, tisa-cel was not found to be superior to ASCT. Further studies will be needed to definitively characterize the relative benefits of CAR-T cell therapies and standard second-line treatments for different subgroups of patients with LBCL. 

An increasing number of effective targeted agents for DLBCL, including novel monoclonal antibodies (tafasitamab) and antibody-drug conjugates (polatuzumab vedotin and loncastuximab teserine), are being used in earlier lines of therapy. Additionally, 2 anti-CD20 bispecific antibodies (epcoritamab and glofitamab) have gained approval for relapsed/refractory DLBCL due to high response rates. Future studies will be needed to determine if treatment with these agents can produce durable remissions like that of CAR-T cell therapy.

There have been several recent developments in the treatment of B-cell lymphoma; however, one of the most significant advances has been the development of chimeric antigen receptor (CAR) T-cell therapy. CAR T-cell therapy is a type of personalized immunotherapy that can help cure some people with aggressive non-Hodgkin lymphoma (NHL), including diffuse large B-cell lymphoma (DLBCL), the most common form of aggressive NHL. CAR T-cell therapy has revolutionized the treatment of hematologic malignancies over the past 5 years, with impressive response rates and durable remissions for patients who previously had no viable options. This strategy is highly effective in patients with relapsed/refractory DLBCL, as well as mantle cell lymphoma, follicular lymphoma, acute lymphoblastic leukemia (ALL), and multiple myeloma, as evidenced by recent regulatory approvals. 

The initial products, axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel)— both FDA approved in 2017—involve administration of autologous T-cells programmed to express a CAR targeting the B-cell marker CD19. 

In 2021, the FDA also approved lisocabtagene maraleucel (liso-cel), a new CAR T-cell therapy for the treatment of adults with relapsed or refractory (nonresponsive) large B-cell lymphoma (LBCL) have been treated with at least 2 prior lines of therapy. These products have design differences, including differences in the costimulatory domain, mechanism of gene/transgene delivery, ability for cryopreservation, and need for T-cell selection.

The CAR T-cell therapy axi-cel demonstrated superior results in the ZUMA-7 clinical trial, which compared CAR T-cell therapy directly to traditional chemotherapy with intended autologous stem cell transplant (ASCT). About 55% of patients were still alive 4 years after receiving axi-cel, compared with 46% of those who initially received the standard treatment for relapsed disease. Based on these results, axi-cel is now the preferred treatment for people whose DLBCL has recurred with 12 months of front-line treatment or who are resistant to standard initial treatment.

Additionally, the BELINDA trial was a randomized phase 3 trial that compared CAR T-cell therapy with liso-cel with second-line chemotherapy with planned ASCT. Like ZUMA-7, this study also demonstrated an improvement in progression-free survival (PFS) compared to standard treatment. As such, CAR T-cell therapy represents the new standard of care for second-line treatment in appropriate patients with refractory or early relapsing LBCL.

There have been several other recent studies on the use of CAR T-cell therapy for B-cell lymphoma. One study, published in Blood Advances (2023), found that receiving a greater number of therapies prior to CAR T-cell therapy is associated with poorer outcomes in patients with aggressive relapsed/refractory B-cell NHL. The study, which included 514 patients from 13 centers treated with CAR-T for aggressive B-cell NHL between 2015 and 2021, found that a greater number of lines of therapy before CAR-T apheresis and bridging therapy were predictive of inferior PFS and overall survival. 

Another study compared 2 CD19-targeting CAR T-cell treatments, axi-cel and tisa-cel, with ASCT in the second line setting for LBCL. The study found that axi-cel was superior to ASCT, with longer median event-free survival and a higher response rate. However, tisa-cel was not found to be superior to ASCT. Further studies will be needed to definitively characterize the relative benefits of CAR-T cell therapies and standard second-line treatments for different subgroups of patients with LBCL. 

An increasing number of effective targeted agents for DLBCL, including novel monoclonal antibodies (tafasitamab) and antibody-drug conjugates (polatuzumab vedotin and loncastuximab teserine), are being used in earlier lines of therapy. Additionally, 2 anti-CD20 bispecific antibodies (epcoritamab and glofitamab) have gained approval for relapsed/refractory DLBCL due to high response rates. Future studies will be needed to determine if treatment with these agents can produce durable remissions like that of CAR-T cell therapy.

The treatment of mantle cell lymphoma (MCL) continues to evolve. In the front-line setting, studies are evaluating the role of novel therapies as well as consolidation with autologous stem cell transplantation. In the relapsed/refractory setting, patients can be considered for treatment with Bruton tyrosine kinase (BTK) inhibitors, other targeted therapies, or chimeric antigen receptor (CAR) T-cell therapy. Other novel therapies, including bispecific antibodies and novel antibody drug conjugates, are being studied as well.

Despite the availability of novel agents, a subset of patients continues to have difficult-to-treat disease and a poor prognosis. Established prognostic tools that aid in identifying high-risk patients include alternations in TP53, high proliferation rates, nonclassic morphology, and the Mantle Cell Lymphoma International Prognostic Index (MIPI) score, which incorporates age, performance status, lactate dehydrogenase levels, and white blood cell count. The Nordic study group recently published a paper which provides additional prognostic information beyond these known variables (Rodrigues et al). They examined MYC expression in a cohort of 251 patients with MCL and structural aberrations in MYC and MYC mRNA levels in a smaller cohort. They found that patients with tumors comprising 20% or more cells with MYC overexpression (MYC^high tumors) vs MYC^low tumors had significantly higher risks for death (adjusted hazard ratio [aHR] 2.03; P = .007) and disease progression (aHR 2.20; P = .04), when adjusted for additional high-risk features. Patients with tumors with concomitant MYC^high expression and TP53/p53 alterations vs MYC^low tumors had a particularly poor prognosis, with significantly increased risks for progression (HR 16.90) and death (HR 7.83) with a median overall survival of only 0.9 years (both P < .001). Though MYC overexpression was rare, this study identified a high-risk group of patients, especially those harboring concurrent TP53 aberrations, that may benefit from novel treatment approaches.

Another study recently aimed to identify patients who are at risk for poor outcomes after treatment with brexucabtagene autoleucel (brexu-cel) infusion. Though brexu-cel is an active therapy for patients with relapsed/refractory MCL, there are known toxicities, including cytokine release syndrome, neurologic toxicity, and hematologic toxicity. Given the potential for prolonged cytopenias and immune suppression, patients are also at risk for severe infections, which currently represent the driving determinant of nonrelapse mortality.¹ The CAR-HEMATOTOX (HT) score was previously found to identify patients who are at increased risk for hematologic toxicity after CAR T-cell therapy in diffuse large B-cell lymphoma.² In the current multicenter observational study, which included 103 patients receiving brexu-cel, the authors reported an association between baseline HT score and outcome in MCL as well. Patients with high (2-7) vs low (0-1) HT scores had significantly longer median duration of severe neutropenia (P < .0001), higher rates of severe infections (P = .001), and lower overall response rates (P = .003). The HT score represented an independent predictor of poor progression-free (aHR 3.7; P < .001) and overall (aHR 5.6; P = .002) survival. This tool may provide a helpful guide when counseling patients on treatment options and allow for more personalized toxicity management.

Despite availability of BTK inhibitors and CAR T-cell therapy for patients with MCL, relapses remain common. As upregulation of phosphoinositide 3-kinase (PI3K) is known to play a critical role in lymphomagenesis, there has been interest in targeting this pathway across lymphoma subtypes. Though PI3K inhibitors have been found to be active agents, they have also been associated with poor tolerability and safety concerns. Parsaclisib is a selective PI3K delta inhibitor that showed encouraging data in the phase 1/2 study in patients with non-Hodgkin lymphoma.³ More recently, the phase 2 CITADEL-205 study, which included adult patients with relapsed or refractory MCL previously treated with one to three systemic therapies, with (n = 53) or without (n = 108) prior BTK inhibitor treatment, was published (Zinazni et al). Patients received 20 mg parsaclisib once daily for 8 weeks followed by either 20 mg parsaclisib once weekly or 2.5 mg parsaclisib once daily. Among BTK inhibitor–naive patients who received parsaclisib once daily, 70.1% (95% CI 58.6%-80.0%) and 15.6% (95% CI 8.3%-25.6%) achieved an objective response and a complete response, respectively, with the median duration of response being 12.1 months (95% CI 9.0 to not evaluable). Responses were not thought to be clinically meaningful in the patients treated with prior BTK inhibitors. Most treatment-emergent adverse events were low grade and manageable by dose interruptions or reductions. A total of 30% of patients required drug discontinuation due to adverse events. Though parsaclisib demonstrated activity in patients with relapsed/refractory MCL, the role of this drug in clinical practice is not clear given the increased use of BTK inhibitors as a preferred second-line therapy and ongoing concerns regarding PI3K inhibitor-related toxicity.

Additional References

1.      Wang Y, Jain P, Locke FL, et al. Brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma in standard-of-care practice: Results from the US Lymphoma CAR T Consortium. J Clin Oncol. 2023;41:2594-2606. doi: 10.1200/JCO.22.01797

2.      Rejeski K, Perez A, Sesques P, et al. CAR-HEMATOTOX: A model for CAR T-cell-related hematologic toxicity in relapsed/refractory large B-cell lymphoma. Blood. 2021;138:2499-2513. doi: 10.1182/blood.2020010543

3.      Forero-Torres A, Ramchandren R, Yacoub A, et al. Parsaclisib, a potent and highly selective PI3Kδ inhibitor, in patients with relapsed or refractory B-cell malignancies. Blood. 2019;133:1742-1752. doi: 10.1182/blood-2018-08-867499

The treatment of mantle cell lymphoma (MCL) continues to evolve. In the front-line setting, studies are evaluating the role of novel therapies as well as consolidation with autologous stem cell transplantation. In the relapsed/refractory setting, patients can be considered for treatment with Bruton tyrosine kinase (BTK) inhibitors, other targeted therapies, or chimeric antigen receptor (CAR) T-cell therapy. Other novel therapies, including bispecific antibodies and novel antibody drug conjugates, are being studied as well.

Despite the availability of novel agents, a subset of patients continues to have difficult-to-treat disease and a poor prognosis. Established prognostic tools that aid in identifying high-risk patients include alternations in TP53, high proliferation rates, nonclassic morphology, and the Mantle Cell Lymphoma International Prognostic Index (MIPI) score, which incorporates age, performance status, lactate dehydrogenase levels, and white blood cell count. The Nordic study group recently published a paper which provides additional prognostic information beyond these known variables (Rodrigues et al). They examined MYC expression in a cohort of 251 patients with MCL and structural aberrations in MYC and MYC mRNA levels in a smaller cohort. They found that patients with tumors comprising 20% or more cells with MYC overexpression (MYC^high tumors) vs MYC^low tumors had significantly higher risks for death (adjusted hazard ratio [aHR] 2.03; P = .007) and disease progression (aHR 2.20; P = .04), when adjusted for additional high-risk features. Patients with tumors with concomitant MYC^high expression and TP53/p53 alterations vs MYC^low tumors had a particularly poor prognosis, with significantly increased risks for progression (HR 16.90) and death (HR 7.83) with a median overall survival of only 0.9 years (both P < .001). Though MYC overexpression was rare, this study identified a high-risk group of patients, especially those harboring concurrent TP53 aberrations, that may benefit from novel treatment approaches.

Another study recently aimed to identify patients who are at risk for poor outcomes after treatment with brexucabtagene autoleucel (brexu-cel) infusion. Though brexu-cel is an active therapy for patients with relapsed/refractory MCL, there are known toxicities, including cytokine release syndrome, neurologic toxicity, and hematologic toxicity. Given the potential for prolonged cytopenias and immune suppression, patients are also at risk for severe infections, which currently represent the driving determinant of nonrelapse mortality.¹ The CAR-HEMATOTOX (HT) score was previously found to identify patients who are at increased risk for hematologic toxicity after CAR T-cell therapy in diffuse large B-cell lymphoma.² In the current multicenter observational study, which included 103 patients receiving brexu-cel, the authors reported an association between baseline HT score and outcome in MCL as well. Patients with high (2-7) vs low (0-1) HT scores had significantly longer median duration of severe neutropenia (P < .0001), higher rates of severe infections (P = .001), and lower overall response rates (P = .003). The HT score represented an independent predictor of poor progression-free (aHR 3.7; P < .001) and overall (aHR 5.6; P = .002) survival. This tool may provide a helpful guide when counseling patients on treatment options and allow for more personalized toxicity management.

Despite availability of BTK inhibitors and CAR T-cell therapy for patients with MCL, relapses remain common. As upregulation of phosphoinositide 3-kinase (PI3K) is known to play a critical role in lymphomagenesis, there has been interest in targeting this pathway across lymphoma subtypes. Though PI3K inhibitors have been found to be active agents, they have also been associated with poor tolerability and safety concerns. Parsaclisib is a selective PI3K delta inhibitor that showed encouraging data in the phase 1/2 study in patients with non-Hodgkin lymphoma.³ More recently, the phase 2 CITADEL-205 study, which included adult patients with relapsed or refractory MCL previously treated with one to three systemic therapies, with (n = 53) or without (n = 108) prior BTK inhibitor treatment, was published (Zinazni et al). Patients received 20 mg parsaclisib once daily for 8 weeks followed by either 20 mg parsaclisib once weekly or 2.5 mg parsaclisib once daily. Among BTK inhibitor–naive patients who received parsaclisib once daily, 70.1% (95% CI 58.6%-80.0%) and 15.6% (95% CI 8.3%-25.6%) achieved an objective response and a complete response, respectively, with the median duration of response being 12.1 months (95% CI 9.0 to not evaluable). Responses were not thought to be clinically meaningful in the patients treated with prior BTK inhibitors. Most treatment-emergent adverse events were low grade and manageable by dose interruptions or reductions. A total of 30% of patients required drug discontinuation due to adverse events. Though parsaclisib demonstrated activity in patients with relapsed/refractory MCL, the role of this drug in clinical practice is not clear given the increased use of BTK inhibitors as a preferred second-line therapy and ongoing concerns regarding PI3K inhibitor-related toxicity.

Additional References

1.      Wang Y, Jain P, Locke FL, et al. Brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma in standard-of-care practice: Results from the US Lymphoma CAR T Consortium. J Clin Oncol. 2023;41:2594-2606. doi: 10.1200/JCO.22.01797

2.      Rejeski K, Perez A, Sesques P, et al. CAR-HEMATOTOX: A model for CAR T-cell-related hematologic toxicity in relapsed/refractory large B-cell lymphoma. Blood. 2021;138:2499-2513. doi: 10.1182/blood.2020010543

3.      Forero-Torres A, Ramchandren R, Yacoub A, et al. Parsaclisib, a potent and highly selective PI3Kδ inhibitor, in patients with relapsed or refractory B-cell malignancies. Blood. 2019;133:1742-1752. doi: 10.1182/blood-2018-08-867499

The treatment of mantle cell lymphoma (MCL) continues to evolve. In the front-line setting, studies are evaluating the role of novel therapies as well as consolidation with autologous stem cell transplantation. In the relapsed/refractory setting, patients can be considered for treatment with Bruton tyrosine kinase (BTK) inhibitors, other targeted therapies, or chimeric antigen receptor (CAR) T-cell therapy. Other novel therapies, including bispecific antibodies and novel antibody drug conjugates, are being studied as well.

Despite the availability of novel agents, a subset of patients continues to have difficult-to-treat disease and a poor prognosis. Established prognostic tools that aid in identifying high-risk patients include alternations in TP53, high proliferation rates, nonclassic morphology, and the Mantle Cell Lymphoma International Prognostic Index (MIPI) score, which incorporates age, performance status, lactate dehydrogenase levels, and white blood cell count. The Nordic study group recently published a paper which provides additional prognostic information beyond these known variables (Rodrigues et al). They examined MYC expression in a cohort of 251 patients with MCL and structural aberrations in MYC and MYC mRNA levels in a smaller cohort. They found that patients with tumors comprising 20% or more cells with MYC overexpression (MYC^high tumors) vs MYC^low tumors had significantly higher risks for death (adjusted hazard ratio [aHR] 2.03; P = .007) and disease progression (aHR 2.20; P = .04), when adjusted for additional high-risk features. Patients with tumors with concomitant MYC^high expression and TP53/p53 alterations vs MYC^low tumors had a particularly poor prognosis, with significantly increased risks for progression (HR 16.90) and death (HR 7.83) with a median overall survival of only 0.9 years (both P < .001). Though MYC overexpression was rare, this study identified a high-risk group of patients, especially those harboring concurrent TP53 aberrations, that may benefit from novel treatment approaches.

Another study recently aimed to identify patients who are at risk for poor outcomes after treatment with brexucabtagene autoleucel (brexu-cel) infusion. Though brexu-cel is an active therapy for patients with relapsed/refractory MCL, there are known toxicities, including cytokine release syndrome, neurologic toxicity, and hematologic toxicity. Given the potential for prolonged cytopenias and immune suppression, patients are also at risk for severe infections, which currently represent the driving determinant of nonrelapse mortality.¹ The CAR-HEMATOTOX (HT) score was previously found to identify patients who are at increased risk for hematologic toxicity after CAR T-cell therapy in diffuse large B-cell lymphoma.² In the current multicenter observational study, which included 103 patients receiving brexu-cel, the authors reported an association between baseline HT score and outcome in MCL as well. Patients with high (2-7) vs low (0-1) HT scores had significantly longer median duration of severe neutropenia (P < .0001), higher rates of severe infections (P = .001), and lower overall response rates (P = .003). The HT score represented an independent predictor of poor progression-free (aHR 3.7; P < .001) and overall (aHR 5.6; P = .002) survival. This tool may provide a helpful guide when counseling patients on treatment options and allow for more personalized toxicity management.

Despite availability of BTK inhibitors and CAR T-cell therapy for patients with MCL, relapses remain common. As upregulation of phosphoinositide 3-kinase (PI3K) is known to play a critical role in lymphomagenesis, there has been interest in targeting this pathway across lymphoma subtypes. Though PI3K inhibitors have been found to be active agents, they have also been associated with poor tolerability and safety concerns. Parsaclisib is a selective PI3K delta inhibitor that showed encouraging data in the phase 1/2 study in patients with non-Hodgkin lymphoma.³ More recently, the phase 2 CITADEL-205 study, which included adult patients with relapsed or refractory MCL previously treated with one to three systemic therapies, with (n = 53) or without (n = 108) prior BTK inhibitor treatment, was published (Zinazni et al). Patients received 20 mg parsaclisib once daily for 8 weeks followed by either 20 mg parsaclisib once weekly or 2.5 mg parsaclisib once daily. Among BTK inhibitor–naive patients who received parsaclisib once daily, 70.1% (95% CI 58.6%-80.0%) and 15.6% (95% CI 8.3%-25.6%) achieved an objective response and a complete response, respectively, with the median duration of response being 12.1 months (95% CI 9.0 to not evaluable). Responses were not thought to be clinically meaningful in the patients treated with prior BTK inhibitors. Most treatment-emergent adverse events were low grade and manageable by dose interruptions or reductions. A total of 30% of patients required drug discontinuation due to adverse events. Though parsaclisib demonstrated activity in patients with relapsed/refractory MCL, the role of this drug in clinical practice is not clear given the increased use of BTK inhibitors as a preferred second-line therapy and ongoing concerns regarding PI3K inhibitor-related toxicity.

Additional References

1.      Wang Y, Jain P, Locke FL, et al. Brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma in standard-of-care practice: Results from the US Lymphoma CAR T Consortium. J Clin Oncol. 2023;41:2594-2606. doi: 10.1200/JCO.22.01797

2.      Rejeski K, Perez A, Sesques P, et al. CAR-HEMATOTOX: A model for CAR T-cell-related hematologic toxicity in relapsed/refractory large B-cell lymphoma. Blood. 2021;138:2499-2513. doi: 10.1182/blood.2020010543

3.      Forero-Torres A, Ramchandren R, Yacoub A, et al. Parsaclisib, a potent and highly selective PI3Kδ inhibitor, in patients with relapsed or refractory B-cell malignancies. Blood. 2019;133:1742-1752. doi: 10.1182/blood-2018-08-867499

Key clinical point: Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who respond to salvage chemotherapy immediately before chimeric antigen receptor (CAR) T-cell therapy administration have better survival outcomes than those with stable or progressive disease, irrespective of the administration timing.

Major finding: Patients who did vs did not respond to salvage chemotherapy immediately before receiving CAR T-cell therapy had significantly longer overall survival rates (P < .001). The number of prior lines of salvage chemotherapy or before CAR T-cell infusion was not significantly associated with overall survival (P = .28).

Study details: This single-center, retrospective study included 76 autologous stem cell transplantation-eligible patients with relapsed or refractory DLBCL who received second-line salvage chemotherapy with curative intent, of whom 30 patients achieved partial or complete response and 34 patients (with or without response) eventually received CAR T-cell therapy.

Disclosures: This study did not disclose the funding source. N Doki declared receiving lecture fees from various sources.

Source: Yagi Y et al. Clinical outcomes in transplant-eligible patients with relapsed or refractory diffuse large B-cell lymphoma after second-line salvage chemotherapy: A retrospective study. Cancer Med. 2023 (Aug 28). doi: 10.1002/cam4.6412

Key clinical point: Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who respond to salvage chemotherapy immediately before chimeric antigen receptor (CAR) T-cell therapy administration have better survival outcomes than those with stable or progressive disease, irrespective of the administration timing.

Major finding: Patients who did vs did not respond to salvage chemotherapy immediately before receiving CAR T-cell therapy had significantly longer overall survival rates (P < .001). The number of prior lines of salvage chemotherapy or before CAR T-cell infusion was not significantly associated with overall survival (P = .28).

Study details: This single-center, retrospective study included 76 autologous stem cell transplantation-eligible patients with relapsed or refractory DLBCL who received second-line salvage chemotherapy with curative intent, of whom 30 patients achieved partial or complete response and 34 patients (with or without response) eventually received CAR T-cell therapy.

Disclosures: This study did not disclose the funding source. N Doki declared receiving lecture fees from various sources.

Source: Yagi Y et al. Clinical outcomes in transplant-eligible patients with relapsed or refractory diffuse large B-cell lymphoma after second-line salvage chemotherapy: A retrospective study. Cancer Med. 2023 (Aug 28). doi: 10.1002/cam4.6412

Key clinical point: Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who respond to salvage chemotherapy immediately before chimeric antigen receptor (CAR) T-cell therapy administration have better survival outcomes than those with stable or progressive disease, irrespective of the administration timing.

Major finding: Patients who did vs did not respond to salvage chemotherapy immediately before receiving CAR T-cell therapy had significantly longer overall survival rates (P < .001). The number of prior lines of salvage chemotherapy or before CAR T-cell infusion was not significantly associated with overall survival (P = .28).

Study details: This single-center, retrospective study included 76 autologous stem cell transplantation-eligible patients with relapsed or refractory DLBCL who received second-line salvage chemotherapy with curative intent, of whom 30 patients achieved partial or complete response and 34 patients (with or without response) eventually received CAR T-cell therapy.

Disclosures: This study did not disclose the funding source. N Doki declared receiving lecture fees from various sources.

Source: Yagi Y et al. Clinical outcomes in transplant-eligible patients with relapsed or refractory diffuse large B-cell lymphoma after second-line salvage chemotherapy: A retrospective study. Cancer Med. 2023 (Aug 28). doi: 10.1002/cam4.6412

Key clinical point: Radiation therapy (RT) as a bridging or salvage approach leads to favorable in‐field control and minimal toxicity in patients with relapsed or refractory mantle cell lymphoma (MCL) undergoing CD19‐targeted chimeric antigen receptor (CAR) T‐cell therapy.

Major finding: At a median RT dose of 15 Gy, the in-field complete response and partial response rates were 86% and 14%, respectively, with a 100% local control rate. Low-dose RT (3.6-6 Gy) achieved similar rates of in-field complete response (70%) and partial response (30%), with the local control rate remaining unchanged. Only one patient experienced grade 3 RT dermatitis after undergoing 40 Gy RT in 16 fractions.

Study details: This retrospective study included 21 patients with relapsed or refractory MCL who were treated with CD19‐targeted CAR T‐cell therapy, of whom 7 patients received prior bridging RT, post‐CAR T salvage RT, or both at 23 sites.

Disclosures: This study did not report any funding source. MJ Frigault declared serving as a consultant for and receiving research funding from various organizations.

Source: Ababneh HS et al. Radiation therapy for patients with relapsed or refractory mantle cell lymphoma undergoing CD19-targeted chimeric antigen receptor T-cell therapy. Hematol Oncol. 2023 (Sep 7). doi: 10.1002/hon.3221

Key clinical point: Radiation therapy (RT) as a bridging or salvage approach leads to favorable in‐field control and minimal toxicity in patients with relapsed or refractory mantle cell lymphoma (MCL) undergoing CD19‐targeted chimeric antigen receptor (CAR) T‐cell therapy.

Major finding: At a median RT dose of 15 Gy, the in-field complete response and partial response rates were 86% and 14%, respectively, with a 100% local control rate. Low-dose RT (3.6-6 Gy) achieved similar rates of in-field complete response (70%) and partial response (30%), with the local control rate remaining unchanged. Only one patient experienced grade 3 RT dermatitis after undergoing 40 Gy RT in 16 fractions.

Study details: This retrospective study included 21 patients with relapsed or refractory MCL who were treated with CD19‐targeted CAR T‐cell therapy, of whom 7 patients received prior bridging RT, post‐CAR T salvage RT, or both at 23 sites.

Disclosures: This study did not report any funding source. MJ Frigault declared serving as a consultant for and receiving research funding from various organizations.

Source: Ababneh HS et al. Radiation therapy for patients with relapsed or refractory mantle cell lymphoma undergoing CD19-targeted chimeric antigen receptor T-cell therapy. Hematol Oncol. 2023 (Sep 7). doi: 10.1002/hon.3221

Key clinical point: Radiation therapy (RT) as a bridging or salvage approach leads to favorable in‐field control and minimal toxicity in patients with relapsed or refractory mantle cell lymphoma (MCL) undergoing CD19‐targeted chimeric antigen receptor (CAR) T‐cell therapy.

Major finding: At a median RT dose of 15 Gy, the in-field complete response and partial response rates were 86% and 14%, respectively, with a 100% local control rate. Low-dose RT (3.6-6 Gy) achieved similar rates of in-field complete response (70%) and partial response (30%), with the local control rate remaining unchanged. Only one patient experienced grade 3 RT dermatitis after undergoing 40 Gy RT in 16 fractions.

Study details: This retrospective study included 21 patients with relapsed or refractory MCL who were treated with CD19‐targeted CAR T‐cell therapy, of whom 7 patients received prior bridging RT, post‐CAR T salvage RT, or both at 23 sites.

Disclosures: This study did not report any funding source. MJ Frigault declared serving as a consultant for and receiving research funding from various organizations.

Source: Ababneh HS et al. Radiation therapy for patients with relapsed or refractory mantle cell lymphoma undergoing CD19-targeted chimeric antigen receptor T-cell therapy. Hematol Oncol. 2023 (Sep 7). doi: 10.1002/hon.3221

Key clinical point: In low endemic areas for hepatitis B surface antigen, patients with past or active hepatitis B virus (HBV) infections have an increased risk for diffuse large B-cell lymphoma (DLBCL).

Major finding: Patients with DLBCL, but not with various types of indolent B-cell non-Hodgkin lymphomas (NHL), had a significantly higher prevalence of chronic (P = .008) and past (P = 0.002) HBV infections vs HBV-negative serology. The DLBCL vs pooled indolent B-cell NHL group had a significantly higher prevalence of chronic (adjusted odds ratio [aOR] 2.8; P = .014) and past (aOR 2.4; P = .0006) HBV infections.

Study details: This retrospective single-center study included patients with DLBCL (n = 253) or different types of indolent B-cell NHL (n = 694) who had either chronic or past HBV infections or no serological evidence for either.

Disclosures: This study was supported by grants from the Intramural Research Program of Sapienza University of Rome. The authors declared no conflicts of interest.

Source: Visentini M et al. High prevalence of past hepatitis B virus infection in diffuse large B cell lymphoma: A retrospective study from Italy. Ann Hematol. 2023 (Aug 31). doi: 10.1007/s00277-023-05412-1

Key clinical point: In low endemic areas for hepatitis B surface antigen, patients with past or active hepatitis B virus (HBV) infections have an increased risk for diffuse large B-cell lymphoma (DLBCL).

Major finding: Patients with DLBCL, but not with various types of indolent B-cell non-Hodgkin lymphomas (NHL), had a significantly higher prevalence of chronic (P = .008) and past (P = 0.002) HBV infections vs HBV-negative serology. The DLBCL vs pooled indolent B-cell NHL group had a significantly higher prevalence of chronic (adjusted odds ratio [aOR] 2.8; P = .014) and past (aOR 2.4; P = .0006) HBV infections.

Study details: This retrospective single-center study included patients with DLBCL (n = 253) or different types of indolent B-cell NHL (n = 694) who had either chronic or past HBV infections or no serological evidence for either.

Disclosures: This study was supported by grants from the Intramural Research Program of Sapienza University of Rome. The authors declared no conflicts of interest.

Source: Visentini M et al. High prevalence of past hepatitis B virus infection in diffuse large B cell lymphoma: A retrospective study from Italy. Ann Hematol. 2023 (Aug 31). doi: 10.1007/s00277-023-05412-1

Key clinical point: In low endemic areas for hepatitis B surface antigen, patients with past or active hepatitis B virus (HBV) infections have an increased risk for diffuse large B-cell lymphoma (DLBCL).

Major finding: Patients with DLBCL, but not with various types of indolent B-cell non-Hodgkin lymphomas (NHL), had a significantly higher prevalence of chronic (P = .008) and past (P = 0.002) HBV infections vs HBV-negative serology. The DLBCL vs pooled indolent B-cell NHL group had a significantly higher prevalence of chronic (adjusted odds ratio [aOR] 2.8; P = .014) and past (aOR 2.4; P = .0006) HBV infections.

Study details: This retrospective single-center study included patients with DLBCL (n = 253) or different types of indolent B-cell NHL (n = 694) who had either chronic or past HBV infections or no serological evidence for either.

Disclosures: This study was supported by grants from the Intramural Research Program of Sapienza University of Rome. The authors declared no conflicts of interest.

Source: Visentini M et al. High prevalence of past hepatitis B virus infection in diffuse large B cell lymphoma: A retrospective study from Italy. Ann Hematol. 2023 (Aug 31). doi: 10.1007/s00277-023-05412-1