Comparative toxicity profile of chimeric antigen receptor T-cell therapy versus bispecific T-cell engagers in multiple myeloma and B-cell lymphomas: A propensity-matched real-world analysis.

e19524 Background: Chimeric antigen receptor T-cell (CAR-T) therapy and bispecific T-cell engagers (BiTEs) are widely used T-cell–redirecting immunotherapies for multiple myeloma and B-cell lymphomas. However, their comparative real-world toxicity profiles have not been widely studied, particularly given differences in treatment intensity and patient selection. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network, a federated database of de-identified electronic health records. Adult patients (≥18 years) with multiple myeloma or B-cell lymphoma treated with CAR-T therapy were compared with those treated with BiTE therapy. Propensity score matching (1:1) was performed on age, sex, race/ethnicity, diagnosis, prior stem cell transplantation, baseline cytopenias, and major comorbidities. Toxicity and healthcare utilization outcomes were assessed at 1, 2, and 5-year follow-up. Results: A total of 6,596 patients were identified (CAR-T: n = 480; BiTE: n = 6,116). After propensity score matching, 342 patients were included in each cohort. 342 patients were included in each cohort. In the matched population, mean age was 63.0 years in the CAR-T cohort and 64.5 years in the BiTE cohort, with a similar proportion of male patients (61.7% vs 61.1%). CAR-T therapy was associated with higher risks of neutropenia at 1 year (RR 2.92, 95% CI 2.02–4.22; p < 0.001), 2 years (RR 2.50, 95% CI 1.78–3.49; p < 0.001), and 5 years (RR 2.32, 95% CI 1.68–3.19; p < 0.001). Hospitalization was more frequent following CAR-T therapy at 1 year (RR 2.34, 95% CI 1.65–3.32; p < 0.001), 2 years (RR 2.24, 95% CI 1.59–3.16; p < 0.001), and 5 years (RR 2.16, 95% CI 1.55–3.01; p < 0.001). Thrombocytopenia occurred more commonly with CAR-T at 1 year (RR 1.48, 95% CI 1.02–2.15; p = 0.036) but not at later intervals, while anemia rates were comparable throughout follow-up. Immune-mediated toxicities were more common with CAR-T therapy, including cytokine release syndrome (RR 2.78, 95% CI 2.01–3.84; p < 0.001) and ICANS (RR 1.81, 95% CI 1.09–3.02; p = 0.021), with differences persisting through 5 years. Sepsis rates were similar between cohorts. Conclusions: In this real-world analysis, CAR-T therapy was associated with a higher burden of neutropenia, immune-mediated toxicity, and hospitalization compared with BiTE therapy across all follow-up intervals. Although prior studies report higher response rates with CAR-T therapy, these benefits must be weighed against its greater toxicity burden. These findings highlight meaningful safety differences between T-cell–redirecting therapies and underscore the importance of individualized treatment decisions in immunotherapy selection.