Rare Toxicities of CAR T-Cell Therapy: Cardiovascular, Hematopoietic and Other Infrequent Adverse Events

Chimeric antigen receptor (CAR) T-cell therapy has proven to be an effective treatment option for various hematological malignancies. Despite the enormous potential of CAR T-cell therapy, there are still challenges to be addressed, including the management of significant toxicities associated with the treatment. The most frequent adverse events associated with CAR T-cell infusion are cytokine release syndrome (CRS), a systemic inflammatory response triggered by rapid CAR T-cell activation and expansion, and immune effector cell-associated neurotoxicity syndrome (ICANS) caused by peripheral immune overactivation, blood–brain barrier dysfunction, and central nervous system (CNS) inflammation. We recently reported on a spectrum of rare side effects of CAR T cells, specifically, toxicities caused by cellular infiltrations and local inflammation in critical sites and damage to neuronal structures or functions. This review article focuses on the less common toxicities of CAR T-cell products, including those related to cardiovascular and hematological complications, as well as other rare side effects. Efforts to understand the underlying mechanisms driving these toxicities and develop strategies to predict, prevent and manage them are crucial for optimizing the safety and efficacy of CAR T-cell therapy in clinical practice. PEER REVIEWED ARTICLE **Peer reviewers:** Prof. Dr Andreas Holbro, University Hospital Basel, Basel, Switzerland Prof. Dr Christoph Renner, Hospital Hirslanden, Zurich, Switzerland Prof. Dr Dr Dominik Schneidawind, University Hospital Zurich, Zurich, Switzerland Received: May 13, 2024; accepted after peer review: June 26, 2024.