Cardiovascular Toxicities with Chimeric Antigen Receptor T-cell Therapy

Chimeric antigen receptor (CAR) T-cell therapy has shown remarkable efficacy in treating highly refractory and relapsing hematological malignancies in pediatric and adult patients. However, this promising therapy is limited by severe and potentially life-threatening toxicities. Cytokine release syndrome (CRS) is the most commonly observed of these toxicities. The cardiovascular manifestations of CRS include tachycardia, hypotension, left ventricular dysfunction, arrhythmias, troponin elevation, cardiogenic shock, and pulmonary edema. Recent data suggest that cardiotoxicities may be transient and reversible in younger patients with few cardiac comorbidities; however, cardiotoxicities may be fatal in older patients with significant cardiac risk factors. The literature remains sparse regarding long-term cardiotoxicities associated with CAR-T cell therapy. Furthermore, consensus guidelines for monitoring and prevention of cardiotoxicities remain illdefined. Therefore, this review will detail the cardiovascular toxicities of CAR T-cell therapy seen in clinical trials and observational studies, summarize treatment approaches for CRS, outline the currently adopted surveillance protocols for CAR T-cell associated cardiotoxicity, and explore the future directions of research in this rapidly emerging field.