Bispecific antibodies (BsAbs) are rapidly reshaping the treatment landscape for relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) and follicular lymphoma, offering an off-the-shelf alternative to CAR-T therapy. New real-world analyses provide important insight into how these therapies compare in both safety and effectiveness, while also highlighting emerging differences among individual BsAbs.
A large retrospective study using the TriNetX research network examined outcomes among patients treated with either CAR-T therapy or BsAbs, focusing on early toxicity and healthcare utilization.1 After careful matching of baseline characteristics, 359 patients were included in each group. The findings point to a consistently more favorable early safety profile with BsAbs. Rates of cytokine release syndrome (CRS), a hallmark toxicity of immune-based therapies, were significantly lower with BsAbs (31.8% vs 59.6%) from an analysis of 0 to 60 days. Similarly, immune effector cell–associated neurotoxicity syndrome (ICANS) occurred less frequently in patients receiving BsAbs (9.4% vs 26%) in an analysis of 0 to 60 days.1
Despite these tolerability advantages, short-term survival favored CAR-T therapy, with higher 90-day overall survival (OS) compared with BsAbs (hazard ratio, 2.99; 95% CI, 1.89-4.73).1 Investigators noted that this difference likely reflects a real-world treatment selection bias, as BsAbs are often used in patients with poorer prognostic features or those ineligible for CAR-T therapy. Importantly, risks of infection and longer-term immune suppression, including hypogammaglobulinemia, were similar between the approaches, underscoring shared immunologic effects.1
Further insight into BsAb use comes from a second TriNetX analysis directly comparing 2 CD20×CD3 bispecific antibodies, epcoritamab and glofitamab, in heavily pretreated R/R DLBCL.2 Among matched cohorts of 205 patients each, glofitamab was associated with improved early survival.2 At 6 months, OS was 68% with glofitamab compared with 56% with epcoritamab, corresponding to a significant reduction in mortality risk.2
Safety profiles between the agents were broadly similar. Rates of CRS, including severe events, did not significantly differ, and ICANS remained low with both therapies. Hematologic toxicities and ICU admissions were also comparable, suggesting similar overall tolerability.2
One notable distinction between patients treated with glofitamab and those treated with epcoritamab was infection risk. Patients treated with glofitamab experienced significantly fewer infections compared with those receiving epcoritamab (38% vs 49%), highlighting a potential advantage in real-world use. Although survival differences beyond 6 months were not statistically significant, trends continued to favor glofitamab, emphasizing the need for longer follow-up.2
Taken together, these findings reinforce the growing role of bispecific antibodies as a safer, more accessible immunotherapy option for patients with B-cell lymphomas, particularly those who may not be candidates for CAR-T therapy. At the same time, differences emerging among individual BsAbs suggest that treatment selection may soon become more nuanced, requiring consideration of both efficacy and safety profiles. As real-world experience continues to expand, these data will be critical in guiding optimal sequencing and selection of immunotherapies in this evolving treatment landscape.