Updated insights on cardiac risks of CD19-directed chimeric antigen receptor T-cell therapy: a pharmacovigilance study

Plain language summaryChimeric antigen receptor T-cell (CAR-T) therapy is effective in a wide spectrum of malignancies. However, the complete cardiotoxicity profile associated with this new treatment has not been characterized. This study systematically analyzed the reported cardiac events of four approved CAR-T agents using the US FDA's Adverse Event Reporting System database. It indicated that the type of cardiac events was broad and overlapped a lot with cytokine release syndrome. Pre-therapy assessment, intensive monitoring and appropriate intervention were critical to reduce the level of cardiac damage or the rate of mortality in patients receiving CAR-T. Aim: Comprehensively characterize the cardiotoxicity of CD19-directed chimeric antigen receptor T-cell (CAR-T) products. Materials & methods: Data between 2017 and 2021 in the US FDA's Adverse Event Reporting System database were utilized. Disproportionality was measured using reporting odds ratio and information component. Hierarchical clustering analysis was performed to explore the relationships among cardiac events. Results: Tisagenlecleucel exhibited the highest percentage of death (53.24%) and life-threatening (13.39%) outcomes. Axicabtagene ciloleucel and tisagenlecleucel were equal in the number of positive signals (n = 15), while the former had excessive reporting of several cardiac events versus the latter, such as atrial fibrillation, cardiomyopathy, cardiorenal syndrome and sinus bradycardia. Conclusion: Several cardiac risks should be considered for CAR-T treatment and these events might vary in frequency and severity following different CAR-T agents.