Real-world toxicity of bispecific antibodies versus CAR-T cell therapy in diffuse large B-cell lymphoma and follicular lymphoma.

Abstract

7033 Background: CAR-T cell therapy and bispecific antibodies (BsAbs) have transformed treatment of relapsed or refractory B-cell lymphomas. While CAR-T toxicities are well characterized, real-world comparative safety data for newer BsAbs remain limited. We compared early and delayed toxicities of CAR-T versus BsAbs in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). Methods: Using the TriNetX Research Network, we conducted a retrospective cohort study of adults with DLBCL or FL treated with BsAbs or CAR-T therapy. 1:1 propensity score matching was performed for demographics, comorbidities, laboratory values, and prior lines of chemotherapy. Outcomes included cytokine release syndrome (CRS) at 14 and 30 days; immune effector cell–associated neurotoxicity syndrome (ICANS) at 30 and 60 days; ICU admission within 90 days; infections within 90 days; hypogammaglobulinemia within 180 days; neutropenia within 90 days; and treatment-related mortality at 90 days. Analyses used Kaplan–Meier methods, hazard ratios (HR), risk ratios (RR), and 95% confidence intervals (CI). Results: A total of 1,110 CAR-T–treated and 897 BsAb-treated patients met inclusion criteria. After matching, 384 patients were included per cohort. Compared with CAR-T, BsAbs were associated with lower CRS at 14 days (RR 0.45, 95% CI 0.37–0.55) and 30 days (RR 0.52, 95% CI 0.44–0.62), and lower ICANS at 30 days (RR 0.30, 95% CI 0.20–0.47) and 60 days (RR 0.36, 95% CI 0.25–0.51). ICU admission within 90 days occurred less frequently with BsAbs (RR 0.56, 95% CI 0.40–0.78). Infection rates at 90 days (RR 1.06, 95% CI 0.87–1.30) and hypogammaglobulinemia at 180 days (RR 0.81, 95% CI 0.65–1.01) were similar between groups. Neutropenia within 90 days was lower with BsAbs (RR 0.55, 95% CI 0.49–0.61). 90-day overall survival was lower with BsAbs (HR 2.99, 95% CI 1.89–4.73), likely driven by treatment selection bias, as BsAbs are frequently used in patients ineligible for CAR-T due to poor performance status, comorbidities, or aggressive disease. Conclusions: In this real-world cohort of DLBCL and FL, BsAbs were associated with substantially lower early immune-mediated toxicity and healthcare utilization compared with CAR-T therapy, while infectious and delayed immune complications were similar. These findings provide important safety data for newer bispecific agents. Outcome Bispecific Antibodies(n = 384) CAR-T(n = 384) HR/RR[95% CI] CRS (0–14 days) 25.3% 56.3% 0.45 [0.37-0.55] CRS (0–60 days) 31.8% 59.6% 0.53 [0.45-0.63] ICANS (0–30 days) 8.1% 22.4% 0.30 [0.20-0.47] ICANS (0–60 days) 9.4% 26.0% 0.36 [0.25-0.51] ICU admission (0–90 days) 12.0% 21.4% 0.56 [0.40-0.78] Infections (0–90 days) 34.6% 32.6% 1.06 [0.87-1.30] Neutropenia (0–90 days) 49.2% 89.6% 0.55 [0.49-0.61] Hypogammaglobulinemia (0–180 days) 27.1% 33.6% 0.81 [0.65-1.01] Overall Survival (0–90 days) 81.4% 93.2% 2.99 [1.89 – 4.73]