Introduction: The emergence of novel immunotherapies and cellular therapies has transformed the treatment landscape for hematological malignancies such as diffuse large B-cell lymphoma (DLBCL). As these therapies become more widely adopted in clinical practice, comparative evidence is needed to inform treatment selection and guide patient care. We conducted a national, real-world analysis of clinical outcomes between current FDA-approved CAR-T cell therapies (CAR-T) and bispecific antibodies (BsAbs) in patients with DLBCL.

Methods: We conducted a retrospective cohort study using real-world data from the TriNetX United States Research Database, a federated network of de-identified electronic health records (EHRs) from over 70 healthcare organizations. The study period included all relevant data from August 1st, 2005, to August 1st, 2025, or a standard 20-year lookback period. Propensity score matching was used to adjust for confounders, and time-to-event analysis was performed using Cox proportional hazards models with additional Kaplan-Meier survival analyses where appropriate. Statistical significance was determined by p < 0.001. Our primary outcome was overall survival, and several additional secondary outcomes were explored.

Results: 107,742 DLBCL patients were identified, of whom 2,840 were exposed to CAR-T only and 199 were exposed to BsAbs only. Propensity score matching identified 190 patients per cohort thereafter. The Cox proportional hazards model demonstrated that DLBCL patients who received CAR-T had greater overall survival than those who received BsAbs (HR 0.431, CI 0.337-0.551, p<0.0001). Median overall survival for CAR-T was 37.8 months, and for BsAbs was 14.3 months; median follow-up time for CAR-T was 15.5 months and for BsAbs was 6.01 months. Furthermore, CAR-T recipients were less likely to progress to further lines of treatment (HR 0.372, CI 0.278-0.497, p<0.0001) at data cutoff.

On secondary analysis, CAR-T was found to have a higher risk of cytokine release syndrome (CRS; RR 1.414, CI 1.081-1.851), immune effector cell-associated neurotoxicity syndrome (ICANS; RR 1.800, CI 1.153-2.811), febrile neutropenia (RR 2.778, CI 1.878-4.108), and pancytopenia (RR 2.121, CI 1.670-2.693) than BsAbs. Lastly, CAR-T use was found to have higher rates of hypogammaglobulinemia (RR 2.000, CI 1.424-2.809), but the rate of IVIG use between cohorts was statistically insignificant.

Conclusion: In this real-world, retrospective multi-cohort analysis, we report comparative outcomes associated with CAR-T versus BsAbs in DLBCL. Most notably, CAR-T demonstrated greater overall survival and a lower likelihood of requiring further lines of therapy; however, CAR-T was also associated with greater hematotoxicity. As the use of these novel agents expands, ongoing evaluation of these analyses will be essential to inform treatment sequencing and optimize patient care.

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2025
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