CARDIOVASCULAR EVENTS ASSOCIATED WITH CAR-T THERAPY (ANALYSIS OF THE FDA ADVERSE EVENTS REPORTING SYSTEM)

Abstract

Background Chimeric Antigen Receptor (CAR-T) cell therapy is approved in the US for treatment of Leukemias/Lymphomas. Multiple cardiovascular adverse events (CVAE) after CAR-T have been noted in small studies. Methods We used the FDA adverse events reporting system (FAERS) to identify all reported adverse events (AEs) associated CAR-T therapies (axicabtagene ciloleucel and tisagenlecleucel) from 2017 to 2019. Reports with missing age and sex were excluded. Cardiovascular (CV) AEs were classified as arrhythmias (supraventricular/ventricular), heart failure (HF), myocardial infarction (MI) and other CVAEs. Multivariable logistic regression was used to identify factors associated with CVAEs. Results A total of 996 reported AEs were observed (39.1% tisagenlecleucel and 60% axicabtagene ciloleucel). Median age was 54 (IQR 21-65) years; 38.9% were females and 91.1% had an FDA-approved indication for CAR-T use. Among these, 196 (19.7% of all AEs) were CVAEs: arrhythmias (77.6%), HF (14.3%), and MI (0.5%). In unadjusted models, there was no association between age, sex, CAR-T type, or indication with reported CVAEs. Reported CVAEs were associated with 30.1% mortality. Association between cytokine release syndrome, neurotoxicity, IL-6 antagonist use, and CVAE is shown in figure. [Figure presented] Conclusion In FAERS, CVAEs were frequently reported with CAR-T use, and are associated with high reported mortality. CRS and neurotoxicity are strongly associated with CVAEs and should prompt cardiovascular work-up.