Chimeric antigen receptor T-cell therapy toxicities.

ABSTRACT

Cancer immunotherapy has greatly advanced in recent years, with chimeric antigen receptor (CAR) T cells emerging as an innovative technology that harnesses the immune system to fight malignant diseases. These genetically engineered T-cells have shown encouraging results for B-cell lymphoid malignancies and are now being explored for other cancer types. However, this novel adoptive cell therapy is associated with a new spectrum of immune-mediated adverse events and toxicities. As CAR T cells recognize and engage tumour cells, cytokines are secreted and activate other immune cells, frequently leading to rapid development of cytokine release syndrome, which can result in acute deterioration of the patient's clinical condition. In many patients, cytokine release syndrome is mild and easy to manage, but others experience persistent fevers accompanied by hypotension and hypoxia, which require management with immune-modulatory agents. Another deleterious effect of cytokines released by effector cells is immune effector cell-associated neurotoxicity syndrome. This syndrome, caused by a disruption of the blood-brain barrier as a consequence of the immune process, can result in rapid deterioration in cognitive function. This is often associated with subtle changes in handwriting, often progressing to loss of memory and concentration and reduced ability to name objects or follow commands. In some cases, the neurological state is further compromised by seizures and in rare instances with fulminant life-threatening cerebral oedema. In this review, we discuss these toxicities, as well as other CAR T-cell-related immune phenomenon, and address their clinical manifestations, grading, and management options.