Comparative cardiovascular and hematologic safety of CAR-T cell therapies and bispecific antibodies: A FAERS-based disproportionality analysis (2022–2024).

444 Background: CAR-T cell therapies and bispecific antibodies are novel immunotherapies for hematologic malignancies. While trials have reported immune-related toxicities, real-world comparative safety data remain limited. Identifying high-risk adverse events (AEs) in clinical practice is crucial for informed decision-making and patient safety. Methods: This retrospective pharmacovigilance study analyzed U.S. FDA Adverse Event Reporting System (FAERS) data from 2022 to 2024. Reports involving CAR-T therapies and bispecific antibodies were extracted and categorized. Descriptive statistics and disproportionality analyses using Reporting Odds Ratios (RORs) with 95% confidence intervals (CIs) were performed. Analyses were conducted in R version 4.5.0. Results: A total of 3,867 AE reports were included, with 2,060 involving CAR-T therapies and 1,807 involving bispecific antibodies. CAR-T recipients had a higher mean age (60.4 years) compared to bispecific users (52.6 years), and males predominated in both groups. Common AEs for CAR-T therapy included cytokine release syndrome (n = 697), decreased neutrophil count (n = 355), and decreased white blood cell count (n = 349). For bispecific antibody users, frequently reported AEs included cytokine release syndrome (n = 339), recurrent acute lymphocytic leukemia (n = 185), and death (n = 176). Disproportionality analysis revealed significantly elevated RORs for CAR-T therapies across a wide range of hematologic and inflammatory events. Notably, the ROR for myelodysplastic syndrome was 25.7 (95% CI: 11.4–57.9), hypophosphatemia 21.0 (8.4–52.8), decreased immunoglobulin G 20.1 (7.4–54.4), hypoalbuminemia 15.8 (7.0–35.8), and elevated C-reactive protein 15.6 (7.2–33.7). Additional elevated risks were observed for decreased lymphocyte count, peripheral edema, decreased appetite, acute myeloid leukemia, decreased platelet count, decreased neutrophil count, elevated gamma-glutamyltransferase, asthenia, decreased white blood cell count, hypocalcemia, disease progression, cough, hypokalemia, and elevated aspartate aminotransferase. These results suggest that CAR-T therapies are associated with a broader and more severe toxicity profile than bispecific antibodies. Conclusions: Compared to bispecific antibodies, CAR-T therapies are associated with substantially higher reporting odds of hematologic and inflammatory adverse events. The consistently elevated RORs across a wide range of toxicities underscore the need for rigorous monitoring and follow-up in patients receiving CAR-T therapy. These findings highlight the utility of FAERS-based pharmacovigilance in identifying post-marketing safety signals and informing clinical decision-making in immunotherapy.