Cardiovascular effects associated with chimeric antigen receptor T cell therapy in cancer patients: A meta-analysis

Abstract

BackgroundAlthough numerous studies confirmed the marked efficacy of chimeric antigen receptor T cells (CAR-T cells) in many hematologic malignancies, severe cardiovascular toxicities remain to be a major obstacle when incorporating this technology. Furthermore, previous individual investigations regarding the cardiovascular toxicities of CAR-T cell therapy also reported controversial conclusions. Therefore, a meta-analysis was performed to further evaluate the impacts of CAR-T cell therapy on cardiovascular toxicities.MethodsThe PubMed, Embase, Web of Science, and ClinicalTrials.gov databases were searched for eligible studies up to April 2022. All analyses were carried out using the R 4.1.0 software.ResultsEventually, 25 related studies consisting of 2,059 patients were enrolled in the current meta-analysis. We discovered that the pooled incidence rate of the all-cause mortality rate was 14.1% and that the pooled incidence rates of overall cardiovascular (CV) events and CV events with cytokine release syndrome (CRS) grade ≥ 2 were 25.6% and 14.2%, respectively. The pooled incidence of hypotension was 28.6%. Further analysis showed that the incidence rates of arrhythmias, cardiovascular dysfunction, heart failure (HF), CV deaths, acute coronary syndrome (ACS), cardiomyopathy, cardiac arrest, and other CV events were 19.2%, 8.0%, 5.3%, 1.8%, 2.5%, 2.9%, 1.3%, and 1.9%, respectively.ConclusionCancer patients treated with CAR-T cell therapy were at risk for cardiovascular toxicities, of which the most common cardiovascular events were arrhythmias, cardiovascular dysfunction, and heart failure. These findings would contribute to achieving more rational and individualized use of CAR-T cells in clinical treatment.

How to Treat Diffuse Large B-Cell Lymphoma

“…More recently, there have been increasing reports of cardiovascular events also associated with CD19-directed CAR-T therapy including hypotension, pulmonary edema, heart failure, arrythmia, and cardiac arrest. 52 , 53 , 54 , 55 , 56 Acute cardiotoxicity occurs mostly in the context of cytokine release syndrome (CRS), which is caused by surge in cytokines due to the activation of immune cells themselves as well as the resultant tumor-cell lysis. The rate of cardiotoxicity generally correlates with the severity of CRS, 54 and a recent study showed lower rates of cardiotoxicity when there was a shorter time between the start of CRS and the administration of IL-6 inhibitor tocilizumab.…”