Cardiovascular toxicities associated with novel cellular immune therapies

Over the past decade, T-cell-directed therapies, including chimeric antigen receptor T-cell (CAR-T) and bispecific T-cell engager (BTE) therapies, have reshaped the treatment of an expanding number of hematologic malignancies, whereas tumor-infiltrating lymphocytes, a recently approved cellular therapy, targets solid tumor malignancies. Emerging data suggest that these therapies may be associated with a high incidence of serious cardiovascular toxicities, including atrial fibrillation, heart failure, ventricular arrhythmias, and other cardiovascular toxicities. The development of these events is a major limitation to long-term survival after these treatments. This review examines the current state of evidence, including reported incidence rates, risk factors, mechanisms, and management strategies of cardiovascular toxicities after treatment with these novel therapies. We specifically focus on CAR-T and BTE therapies and their relation to arrhythmia, heart failure, myocarditis, bleeding, and other major cardiovascular events. Beyond the relationship between cytokine release syndrome and cardiotoxicity, we describe other potential mechanisms and highlight key unanswered questions and future directions of research.