A retrospective pharmacovigilance analysis based on the FAERS database reveals sex-associated differences in toxicities of CAR T-cell therapy.

Chimeric antigen receptor (CAR) T-cell therapy has significantly advanced treatment outcomes for hematological malignancies; however, therapy-associated toxicities are often severe and sex-related differences in toxicity remain under-investigated. Here, we extract data from FDA Adverse Event Reporting System (FAERS) to evaluate sex-associated differences in CAR T-cell therapy toxicities. Among 7700 cases, females show higher reporting odds of cytokine release syndrome (CRS), with a reporting odds ratio (ROR) of 1.10 and a confidence interval (CI) of [1.00, 1.20], as well as leukemias (ROR = 1.34; CI [1.05, 1.70]). Elevated reporting odds in females are observed across multiple organ systems. Comparisons across cancer treatments indicate that sex-associated reporting patterns in CAR T-cell therapy cannot be attributed to baseline sex differences across cancer therapies. Stratified analyses further identify heterogeneity by cancer type and CAR T product. These results highlight distinct sex-associated toxicity patterns and may support incorporating sex into toxicity management.