Association of cardiotoxicity with chimeric antigen receptor T-cell (CAR-T) therapy: A systematic review.

Abstract

e19522 Background: Chimeric antigen receptor (CAR) T-cells represent a novel and highly effective option for the treatment of relapsed/refractory hematologic malignancies. However, CAR T-cell therapy also creates the potential for unpredictable and serious side effects, particularly cytokine release syndrome (CRS) and cardiovascular ischemia. Recent evidence has shown that there is an increasing recognition of arrhythmias, heart failure, and left ventricular dysfunction during the post-infusion period. Methods: A systematic review of published literature was performed in accordance with PRISMA guidance. PubMed/MEDLINE, Embase, Scopus, and the Cochrane Library were searched from inception to the most recent available date for studies reporting cardiovascular adverse events following CAR T-cell therapy. Eligible studies included clinical trials, observational cohorts, registry-based studies, and case series in adult or pediatric populations. Data was extracted on patient characteristics, CAR-T product type, CRS severity, cardiovascular event definitions, diagnostic modalities, timing of events, therapeutic interventions, and clinical outcomes. Risk of bias was assessed using study-design appropriate tools. Results: There were 20 studies included in our analysis. Pooled incidence of cardiovascular events observed was approximately 19.68% with arrhythmias (7.70%); heart failure (5.73%); and decreased left ventricular ejection fraction (3.86%) representing the most commonly reported cardiovascular events. Troponin elevation was reported in 23.61% of patients while NT-proBNP elevation occurred in 9.4% of patients studied. Most commonly, cardiovascular toxicity occurs shortly after CAR T-cell infusion and is frequently reported alongside systemic inflammatory toxicity/CRS. Higher CRS grade, elevated inflammatory markers, and baseline cardiovascular comorbidities were consistently associated with increased risk of cardiotoxicity. Management strategies reported included early CRS-directed therapy, hemodynamic support, temporary interruption of cardiotoxic co-medications, and treatment for arrhythmias and ventricular dysfunction. Conclusions: In summary, CAR T-cell therapy-associated cardiotoxicity is a clinically relevant event for approximately 1 in 5 patients; arrhythmias and heart failure represent the most prevalent phenotypes of this form of toxicity. Cardiac biomarker elevation is very common and provides an avenue for accurately detecting early development of toxicity, particularly among patients at risk for the development of cardiotoxicity. Establishing clear definitions for evaluating cardiotoxicity, along with developing surveillance and clinical management strategies within an integrated cardio-oncology clinical pathway, are essential for facilitating early detection and improving prognosis.