Abstract
Introduction: The emergence of novel immunotherapies and cellular therapies has transformed the treatment landscape for hematological malignancies such as multiple myeloma (MM). 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 multiple myeloma.
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: 176,183 MM patients were identified, of whom 1,556 were exposed to CAR-T only and 1,173 were exposed to BsAbs only. Propensity score matching identified 959 patients per cohort thereafter. The Cox proportional hazards model demonstrated that MM patients who received CAR-T had greater overall survival than those who received BsAbs (HR 0.622, CI 0.525-0.737, p<0.0001). Median overall survival for CAR-T was 60.7 months and had not yet been met for BsAbs; however, median follow-up time for CAR-T recipients was 16.3 months, whereas BsAbs recipients was 9.80 months. CAR-T recipients were also more likely to require further lines of treatment (HR 4.233, CI 3.537-5.066, p<0.0001) at data cutoff.
On secondary analysis, CAR-T was found to have a higher risk of cytokine release syndrome (CRS; RR 1.980, CI 1.749-2.241), immune effector cell-associated neurotoxicity syndrome (ICANS; RR 1.432, CI 1.206-1.961), all-cause seizures (RR 2.500, CI 1.628-3.839), febrile neutropenia (RR 3.130, CI 2.609-3.756), anemia (RR 1.268, CI 1.133-1.419), thrombocytopenia (RR 1.488, CI 1.320-1.677), and pancytopenia (RR 1.898, CI 1.734-2.077) than BsAbs. Lastly, CAR-T use was found to have higher rates of hypogammaglobulinemia (RR 1.172, CI 1.071-1.282), 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 multiple myeloma. Most notably, CAR-T demonstrated greater overall survival, but BsAbs demonstrated a lower likelihood of requiring further lines of therapy. 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.
