Cardiotoxicity of T cell immunotherapies

Abstract

T cell immunotherapies offer a new approach to cancer therapy. Chimeric antigen receptor (CAR) T cell therapy is the most prolific of these treatments, leveraging genetically engineered T cells to augment the antitumour response. Bispecific antibodies, T cell receptor-engineered T cells and tumour-infiltrating lymphocytes have also emerged as novel T cell therapies with therapeutic benefit. As the variety of T cell therapies and indications for their use expand, a nuanced understanding of potential haemodynamic sequelae and cardiovascular toxicities is required. T cell activation can lead to massive cytokine release and excessive inflammation, termed cytokine release syndrome (CRS). Like other inflammatory syndromes, CRS can lead to cardiovascular complications, including arrhythmias, myocardial infarction and heart failure, with an incidence of cardiovascular events as high as 20% among patients who develop high-grade CRS. In this Review, we summarize the mechanisms, epidemiology and management of T cell therapy-associated CRS and subsequent cardiotoxicity. We also explore how an improved understanding of CAR T cell therapy, and other emerging T cell-based treatments, will inform the prevention and management of adverse cardiovascular events. As the indications for T cell immunotherapies, particularly chimeric antigen receptor T cell therapy, continue to expand, a nuanced understanding of their potential adverse effects is required. In this Review, Raddatz and colleagues summarize the mechanisms, epidemiology and management of T cell therapy-associated cytokine release syndrome and subsequent cardiotoxicity.