Predictive factors and baseline risk stratification for CAR-T cell therapy-related cardiovascular toxicity

Abstract Background/ Introduction Baseline cardiovascular (CV) risk stratification is an essential part of the management of patients undergoing potential cardiotoxic anticancer therapies. Chimeric antigen receptor (CAR)-T cells represent a revolutionary therapy for haematologic malignancies that carries a non-negligible risk of CV adverse events (CVAE). Purpose We sought to identify predictors of CAR-T cell-related CVAE and develop a risk stratification score. Methods We performed a meta-analysis of studies reporting differences in baseline clinical, biomarker, echocardiographic and pharmaceutical treatment-related factors between patients who developed CAR-T cell-related CVAE and those who did not. We subsequently used the pooled relative risks (RR) of significant predictors to build a risk stratification score. Results We identified 12 relevant studies comprising 1,354 patients with haematologic malignancies, the majority of which were treated with CD19- directed CAR-T cell therapy, of whom 228 (16,8%) developed CVAE. Significant predictors of CAR-T cell-related CVAE included coronary artery disease RR=2.27 (95% confidence interval, 1.46-3.51), hyperlipidaemia 1.57 (1.14-2.15), diabetes 1.59 (1.13-2.24), hypertension 1.45 (1.18 – 1.77), atrial fibrillation 2.42 (1.51-3.88), heart failure 2.74 (1.62-4.61) and smoking 1.40 (1.10-1.79). The resulting risk prediction score, incorporating the above seven factors, called CART-7, ranges from 0 to 33, with a score of 0-8 indicating low risk, 9-17 moderate risk, 18-25 high risk and 26-33 very high risk. Conclusion Seven baseline CV conditions were significantly associated with CAR-T cell therapy; the resulting prediction score, CART-7, could be used for baseline risk stratification for patients scheduled for this therapy.Graphical Summary Forest Plots