Chimeric Antigen Receptor (CAR) T-Cell Therapy and Cardiovascular Risks

Chimeric antigen receptor (CAR) T-cell therapy is a personalized, genetically engineered cellular therapy that has revolutionized the treatment of refractory multiple myeloma and large B-cell lymphoma. However, its use has been associated with significant cardiovascular morbidity and mortality, including major adverse cardiovascular events (MACE), which pose a risk for the overall treatment outcome of the underlying malignancy. A better understanding of risk factors for these cardiovascular complications is essential for prevention and treatment of such adverse events.

At #AHA22, the cardiovascular complications observed in patients receiving CAR T therapy were discussed. UT Southwestern’s Ari Bennett, M.D., reported an increased prevalence of arrhythmias, including electrical storm. A multicenter registry of patients led by Weill Cornell Medical Center's Syed Saad Mahmood, M.D., M.P.H., revealed an increased incidence of cardiovascular events as defined by the composite endpoint of cardiogenic shock, clinical heart failure, myocardial infarction, and arrhythmia following CAR T-cell infusion in patients with underlying cardiac dysfunction. Alan Baik, M.D., from UC San Francisco, discussed research on immunocellular oncological therapies, including the expanding spectrum of CAR T, such as genetically engineered cellular therapies targeting myocardial fibrosis.

One of us (ME) presented findings from a single-center retrospective analysis of patients at UT Southwestern receiving CAR T-cell therapy. We assessed multiple potential risk factors for MACE, including age, sex, body mass index, coronary artery calcium, lipid profiles, baseline medications, preceding anthracycline or carfilzomib exposure, cancer type, cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), tocilizumab, and baseline echocardiographic parameters. We found that elevated levels of inflammation, specifically C-reactive protein (CRP) levels, were the strongest predictors of MACE. CRS and ICANS grades were also associated with MACE. Interestingly, baseline echocardiographic parameters were not different between patients who did or did not experience MACE. Based on these findings, we hypothesized that monitoring inflammatory markers, and implementing anti-inflammatory strategies, may decrease the incidence of MACE in patients undergoing CAR T-cell therapy, laying the foundation for future studies of these strategies.