Key Clinical Summary

• Real-world matched data showed bispecific antibodies (BsAbs) were associated with significantly lower rates of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), ICU admission, and neutropenia compared with CAR T therapy in patients with diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL).
• Infection and delayed immune complications were comparable between treatment groups, with similar rates of infections and hypogammaglobulinemia.
• Lower 90-day overall survival was observed in the BsAb cohort, which investigators noted was likely influenced by treatment selection bias because BsAbs are often used in patients who are ineligible for CAR T therapy.

A retrospective real-world analysis using the TriNetX Research Network found that bispecific antibodies were associated with substantially lower early immune-mediated toxicities compared with CAR T cell therapy in adults with relapsed or refractory DLBCL and FL. Investigators reported that infectious complications and delayed immune effects were similar between treatment groups, providing important safety data for newer bispecific therapies.

Early Toxicity and Safety Outcomes in DLBCL and Follicular Lymphoma

Researchers analyzed adults with DLBCL or FL treated with either BsAbs or CAR T therapy using the TriNetX Research Network. Following 1:1 propensity score matching for demographics, comorbidities, laboratory values, and prior chemotherapy exposure, 384 patients were included in each treatment cohort.

Compared with CAR T therapy, BsAbs were associated with significantly lower rates of CRS. CRS occurred in 25.3% of patients receiving BsAbs vs 56.3% of patients receiving CAR T therapy within 14 days (risk ratio [RR], 0.45; 95% CI, 0.37-0.55). At 30 days, CRS rates remained lower with BsAbs (31.8% vs 59.6%; RR, 0.52; 95% CI, 0.44-0.62).

ICANS was also less common with bispecific antibodies. ICANS occurred in 8.1% vs 22.4% of patients at 30 days (RR, 0.30; 95% CI, 0.20-0.47) and in 9.4% vs 26.0% at 60 days (RR, 0.36; 95% CI, 0.25-0.51) for BsAbs and CAR T therapy, respectively.

Health care utilization also differed between groups. ICU admission within 90 days occurred in 12.0% of patients treated with BsAbs compared with 21.4% of those receiving CAR T therapy (RR, 0.56; 95% CI, 0.40-0.78). Neutropenia was likewise less frequent with BsAbs (49.2% vs 89.6%; RR, 0.55; 95% CI, 0.49-0.61).

In contrast, infection rates within 90 days were similar between groups (34.6% vs 32.6%; RR, 1.06; 95% CI, 0.87-1.30), as were rates of hypogammaglobulinemia within 180 days (27.1% vs 33.6%; RR, 0.81; 95% CI, 0.65-1.01).

Clinical Relevance of BsAbs vs CAR T Therapy

The findings suggest that bispecific antibodies may offer a more favorable early safety profile than CAR T therapy in routine clinical practice for patients with relapsed or refractory DLBCL and FL. Lower rates of CRS, ICANS, ICU admission, and neutropenia may have important implications for toxicity management and health care resource utilization.

At the same time, clinicians should interpret survival findings cautiously. Ninety-day overall survival was lower among patients treated with BsAbs (hazard ratio, 2.99; 95% CI, 1.89-4.73). Investigators noted that this difference was likely driven by treatment selection bias because bispecific antibodies are frequently administered to patients who are ineligible for CAR T therapy due to poor performance status, significant comorbidities, or aggressive disease rather than reflecting an inherent difference in treatment efficacy.

Overall, the analysis provides additional real-world safety data supporting the use of newer bispecific antibodies while reinforcing the importance of considering patient selection when comparing outcomes across treatment modalities.

Study Conclusions From the Investigators

The investigators concluded that, in this real-world cohort of patients with DLBCL and FL, BsAbs were associated with substantially lower early immune-mediated toxicity and reduced health care utilization compared with CAR T therapy, while infectious complications and delayed immune effects were similar between treatment groups. They stated that these findings provide important real-world safety data for newer bispecific agents.

Supporting Treatment Decisions With Real-World Evidence

This propensity score–matched real-world analysis demonstrates that bispecific antibodies were associated with lower rates of early treatment-related toxicities than CAR T therapy in patients with DLBCL and FL. Although overall survival differed between groups, investigators attributed this finding to treatment selection bias, underscoring the value of these data in informing toxicity management and treatment decision-making.

Reference

Siva NK. Real-world toxicity of bispecific antibodies versus CAR-T cell therapy in diffuse large B-cell lymphoma and follicular lymphoma. Presented at: ASCO 2026; May 29-June 2, 2026. Chicago, IL.