Abstract Body (Do not enter title and authors here): Background: Chimeric antigen receptor T-cell (CAR-T) and bispecific T-cell engager (BiTE) therapies are T-cell engaging treatments with expanding indications in hematologic malignancies, particularly relapsed/refractory multiple myeloma (MM). BiTE agents are also under investigation for first line use and solid tumors. While their efficacy is established, immune-related adverse events (AEs), especially cytokine release syndrome (CRS) and downstream cardiovascular effects, pose clinical challenges. The cardiovascular sequelae of CRS remain under-characterized, with limited comparative data across therapies.

Methods: The FDA Adverse Event Reporting System (FAERS) was queried for AEs linked to five MM-approved immunotherapies: idecabtagene vicleucel and ciltacabtagene autoleucel (CAR-Ts); teclistamab, talquetamab, and elranatamab (BiTEs). Reports were filtered by “plasma cell myeloma” and the AE term “cytokine release syndrome”. Disproportionality metrics including reporting odds ratio (ROR), proportional reporting ratio (PRR), and Bayesian information component were calculated for each drug and pooled by class. Significance was assessed via log(ROR) comparison.

Results: Of 45,285 MM-related AEs, 1,379 (3.0%) were CRS. RORs were highest for idecabtagene (65.7; 55.9–76.9), followed by ciltacabtagene (11.1; 9.29–13.29). BiTE agents showed lower RORs: teclistamab (8.59; 7.42–9.95), talquetamab (6.93; 5.3–9.04), and elranatamab (6.15; 4.77–7.93). Pooled RORs demonstrated a ~3.9-fold higher CRS signal with CAR-Ts (29.9; 26.5–33.6) than BiTEs (7.71; 6.87–8.64; p < 0.00001). Pooled Bayesian values further confirmed this disparity: CAR-T (3.73; 3.37–4.14) vs. BiTEs (2.52; 2.25–2.82).

Conclusion: CAR-T therapies exhibit significantly higher CRS pharmacovigilance signals than BiTE agents in MM, suggesting higher cardiotoxic potential. These findings support CV risk stratification in treatment selection and underscore the need for prospective cardio-oncology registries to validate real-world toxicity patterns.