BACKGROUND : Chimeric Antigen Receptor (CAR-T) cell therapy is approved in the US for the treatment of Acute Lymphocytic Leukemia and aggressive B-Cell Lymphomas. Multiple cardiovascular adverse events (CVE) associated with CAR-Ts have been observed in small studies, but no large-scale studies exist.

METHODS : Leveraging the FDA adverse events reporting system (FAERS), we identified all reported adverse events (AEs) associated with CAR-T therapy (tisagenlecleucel, and axicabtagene ciloleucel) from 2017-2019. Reports with missing age and sex were excluded. CVEs were classified into arrhythmias, heart failure (HF), myocardial infarction (MI), and other CVE. Logistic regression and hierarchical clustering were used to identify factors associated with CVEs.

RESULTS : A total of 996 reported AEs were observed (39.1% associated with tisagenlecleucel, and 60% with axicabtagene ciloleucel). Of all patients experiencing AEs, the median age was 54 (IQR 21-65) years; 38.9% were females. 19.7% (196) of all AEs reported to the FDA were CVEs. The most common CVEs were arrhythmia (77.6%), followed by HF (14.3%) and MI (0.5%). In adjusted analysis a positive association was observed between those presenting with CVE with neurotoxicity [OR = 1.76 (95% CI = 1.20 - 2.60), p = 0.004]. Additionally, when both CVE and cytokine release syndrome (CRS) are present, neurotoxicity is the most common non-cardiac AE, which clusters with them [Jaccard Similarity: 73.1]. The mortality rate was 21.1% overall, but 30.1% for those reporting CVEs.

CONCLUSIONS : In FAERS, reported CVEs with CAR-T are associated with high reported mortality. The development of either CRS or neurotoxicity should prompt vigilance for cardiovascular events.