Updated two-year overall survival and toxicity outcomes of BCMA CAR-T therapy compared with teclistamab in multiple myeloma.

7527 Background: B-cell maturation antigen (BCMA) targeted chimeric antigen receptor T-cell therapy (CAR-T) and bispecific antibodies have transformed the treatment landscape for relapsed or refractory multiple myeloma. In a prior real-world study, CAR-T therapy was associated with improved short-term overall survival compared with teclistamab; however, follow-up was limited to less than one year. Longer-term comparative outcomes between these modalities remain insufficiently characterized. This sequel study evaluates the updated two-year overall survival and toxicity outcomes. Methods: We conducted a retrospective cohort study using the TriNetX US Collaborative Network, comprising data from over 70 healthcare institutions in the United States, to identify patients with multiple myeloma treated between 2021 and 2023 with either CAR-T therapy (ciltacabtagene autoleucel cilta-cel or idecabtagene vicleucel ide-cel) or teclistamab. Patients who received other bispecific antibodies, including elranatamab, talquetamab, or linvoseltamab, were excluded. Two mutually exclusive cohorts were defined: patients who received CAR-T therapy without prior or subsequent teclistamab and patients who received teclistamab without prior or subsequent CAR-T therapy. Propensity score matching was performed to balance baseline demographics, comorbidities, prior therapies, and laboratory values. HR and 95% CI were estimated using Cox proportional hazards models for two-year overall survival, cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS). Results: A total of 351 CAR-T cell therapy recipients and 507 teclistamab recipients were included. After propensity score matching, 227 patients were retained in each cohort, with well-balanced baseline characteristics, including demographics (mean age: 65 years, White: 74%, male: 53%), comorbidities, and prior multiple myeloma treatments, including immunomodulatory drugs, proteasome inhibitors, dexamethasone, and anti-CD38 antibodies. Mean follow-up durations were comparable between the CAR-T and teclistamab cohorts at 524 and 438 days, respectively. CAR-T therapy was associated with significantly improved two-year overall survival compared with teclistamab (HR: 0.61, 95% CI: 0.43-0.87, p=0.005). In contrast, CAR-T therapy was associated with higher risks of CRS (HR: 1.48, 95% CI: 1.12-1.96, p=0.003) and ICANS (HR: 2.02, 95% CI: 1.20-3.41, p=0.007). Conclusions: In this extended two-year real-world analysis, CAR-T therapy was associated with superior overall survival compared with teclistamab, albeit with increased immune-mediated toxicities. These findings build upon prior short-term data and underscore the need for prospective studies directly comparing BCMA-targeted treatment strategies across longer follow-up intervals.