CAR T-Cell Therapy and Bispecific Antibodies Diverge in Relapsed or Refractory DLBCL

Key Clinical Summary

• Recent phase 3 trials moved chimeric antigen receptor (CAR) T-cell therapy into the second-line setting for large B-cell lymphoma, potentially shifting bispecific antibody use later in treatment sequencing. 
• Across indirect comparisons and registry data, CAR T-cell products generally showed higher progression-free and overall survival than bispecific antibodies in relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL). 
• Bispecific antibodies demonstrated lower rates of severe cytokine release syndrome and neurotoxicity, with off-the-shelf availability and outpatient feasibility that may reduce logistical burden. 

Recent evidence highlights important differences between CAR T-cell therapy and bispecific antibodies in R/R DLBCL, with implications for sequencing, toxicity management, access, and payer decision-making. A review in Cancer Medicine summarizes efficacy, safety, and operational tradeoffs as these immunotherapies reshape care.

Main Findings

The review notes that second-line CAR T-cell therapy has gained momentum after the phase 3 ZUMA-7 trial of axicabtagene ciloleucel and the TRANSFORM trial of lisocabtagene maraleucel showed superior event-free survival vs salvage chemotherapy followed by autologous stem-cell transplant. This shift may place CAR T-cell therapy before bispecific antibodies in treatment sequencing.

In R/R DLBCL, efficacy signals favored CAR T-cell therapy in available indirect comparisons. One matching-adjusted indirect comparison reported median progression-free survival of 12.5 months for axicabtagene ciloleucel vs 4.4 months for epcoritamab. In the DESCAR-T registry, 1-year progression-free survival was 46.6% with axicabtagene ciloleucel and 33.2% with tisagenlecleucel; corresponding 1-year overall survival rates were 63.5% and 48.8%, respectively.

By comparison, bispecific antibody outcomes were generally lower, though active. Reported overall response rates ranged from 52% to 73.4% for epcoritamab and 52% for glofitamab, with complete response rates ranging from 36% to 48.5% for epcoritamab and 39% for glofitamab. Meta-analysis data cited in the review showed 1-year overall survival for bispecific antibodies ranging from 32% to 50%.

Safety profiles differed substantially. The review reports grade 3 or higher cytokine release syndrome rates of 4% to 22% with CAR T-cell therapy vs 2% to 8% with bispecific antibodies. Grade 3 or higher neurotoxicity was reported at 3% to 12% with CAR T-cell therapy and 1% to 3% with bispecific antibodies. Grade 3 or higher infections occurred in 15% to 20% of CAR T-cell cohorts and 10% to 15% of bispecific antibody trials.

Clinical Implications

For managed care stakeholders, the review underscores a classic tradeoff: higher efficacy and potential durability with CAR T-cell therapy vs lower acute toxicity and easier access with bispecific antibodies.

Reference

Abou DS, Thalib HI, Akil F, et al. Bispecific antibodies versus chimeric antigen receptor t-cell therapy in relapsed/refractory diffuse large b-cell lymphoma: a comparative narrative review of efficacy, safety, and accessibility. Cancer Med. 2026;15(2): e71562. doi:10.1002/cam4.71562