Comparative effectiveness and toxicity of CAR-T therapy versus blinatumomab in adult B-cell acute lymphoblastic leukemia: A real-world propensity-matched analysis.

6551 Background: Chimeric antigen receptor T-cell (CAR-T) therapy and blinatumomab are established treatment options for relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). While CAR-T therapy offers durable disease control, it is associated with significant immune-mediated toxicities, including cytokine release syndrome (CRS) and neurotoxicity. Comparative real-world data evaluating long-term mortality and toxicity outcomes between CAR-T therapy and blinatumomab remain limited. Methods: We conducted a retrospective cohort study using the TriNetX Analytics Network. Adult patients with B-cell acute lymphoblastic leukemia treated with either CAR-T therapy or blinatumomab were identified. Propensity score matching (1:1) was performed to balance baseline demographic and clinical characteristics, yielding 306 patients in each cohort. Primary outcomes included all-cause mortality at 1 and 3 years. Secondary outcomes included cytokine release syndrome at 1 year and neurotoxicity (including delirium, encephalopathy, and altered mental status) at 3 months, 1 year, and 3 years. Outcomes were assessed using risk ratios (RR), odds ratios (OR), Kaplan–Meier survival analysis, and Cox proportional hazards models. Results: After propensity matching, 612 patients were analyzed (306 per cohort). At 1 year, all-cause mortality was significantly higher with CAR-T than blinatumomab (50.98% vs 17.97%; RR 2.84, 95% CI 2.18–3.69; p<0.0001). Kaplan–Meier analysis showed inferior survival with CAR-T (HR 3.48, 95% CI 2.56–4.74; log-rank p<0.0001). This excess mortality persisted at 3 years (52.61% vs 18.95%; RR 2.78, 95% CI 2.15–3.58; p<0.0001; HR 3.43, 95% CI 2.54–4.63). CAR-T was associated with higher cytokine release syndrome at 1 year (20.59% vs 5.88%; RR 3.50, 95% CI 2.12–5.77; p<0.0001). Neurotoxicity was consistently more frequent with CAR-T: 27.78% vs 13.40% at 3 months (RR 2.07, 95% CI 1.48–2.91; p<0.0001), 25.16% vs 11.44% at 1 year (RR 2.20, 95% CI 1.52–3.18; p<0.0001), and 27.78% vs 13.40% at 3 years (RR 2.07, 95% CI 1.49–3.15; p<0.0001). Kaplan–Meier analyses confirmed a persistently higher cumulative neurotoxicity risk with CAR-T across all time points. Conclusions: In this large real-world propensity-matched analysis, CAR-T therapy for B-cell ALL was associated with significantly higher short- and long-term mortality compared with blinatumomab, as well as markedly increased risks of cytokine release syndrome and neurotoxicity. These findings highlight the substantial toxicity burden associated with CAR-T therapy in routine clinical practice and underscore the importance of careful patient selection, early toxicity recognition, and risk-benefit stratification when choosing between advanced immunotherapeutic options for B-ALL.