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) therapy have reshaped the treatment of an expanding number of hematologic malignancies, while tumor infiltrating lymphocytes (TILs), a recently approved cellular therapy, targets solid tumor malignancies. Emerging data suggests that these therapies may be associated with a high incidence of serious cardiotoxicities, including atrial fibrillation, heart failure, ventricular arrhythmias, and other cardiovascular toxicities. The development of these events is a major limitation to long-term survival following these treatments. This review examines the current state of evidence, including reported incidence rates, risk factors, mechanisms, and management strategies of cardiovascular toxicities following treatment with these novel therapies. We specifically focus on CAR-T, BTE, and their relation to arrhythmias, 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.