Cardiac adverse events after Chimeric Antigen Receptor (CAR) T cell therapies: an updated systematic review and meta-analysis

Abstract

Purpose: Chimeric antigen receptor (CAR) T-cell therapy is a new revolutionary method for treating refractory or relapsed hematologic malignancies, CAR T-cell therapy has been associated with cytokine release syndrome (CRS) and cardiotoxicity. We directed a systematic review and meta-analysis to determine the incidence and predictors of cardiovascular events (CVE) with CAR T-cell therapy. Methods: We investigated PubMed, Embase, Cochrane Library, and ClinicalTrials.gov for studies reporting cardiovascular outcomes in CAR-T cell recipients. The study protocol was listed in the International Prospective Register of Systematic Reviews (PROSPERO ID: CRD42023478602). Twenty-three studies were included in this study. Results: The pooled incidence of CVE was 54% for arrhythmias, 30% for heart failure, 20% for cardiomyopathy, 10% for acute coronary syndrome, and 7% for cardiac arrest. Patients with CVE had a higher incidence of cytokine release syndrome grade ≥ 2 (RR 2.36, 95% CI 1.86–2.99). The incidence of cardiac mortality in our meta-analysis was 2% (95% CI: 1%–3%). Left ventricular ejection fraction decline was greater in the CVE group (-9.4% versus -1.5%, p < 0.001). Cardiac biomarkers like BNP, CRP, creatinine, and ferritin were also elevated. Conclusions: CAR T-cell therapy commonly leads to cardiotoxicity, mediated by cytokine release syndrome. Vigilant monitoring and tailored treatments are crucial to mitigate these effects. Importantly, there's no significant difference in cardiac mortality between groups, suggesting insights for optimizing preventive interventions and reducing risks after CAR T-cell therapy. Graphical Abstract: (Figure presented.).