Neurotoxicities After CAR T-Cell Immunotherapy

Abstract Neurologic adverse events occur in a high proportion of patients treated with CD19-directed chimeric antigen receptor (CAR) T-cells for B-cell malignancies and are also observed after treatment with CD22- and B-cell maturation antigen–targeted CAR T-cell therapy. Clinical manifestations such as delirium, language disturbance, and seizures develop in conjunction with or soon after cytokine release syndrome and are usually reversible; however, in rare cases, fatal neurotoxicity can occur. Data from patients and animal models of neurotoxicity demonstrate high levels of key cytokines in the blood and cerebrospinal fluid. Monocyte/macrophage and endothelial cell activation with compromise of the blood-brain barrier appears to contribute to the pathogenesis. Treatment with corticosteroids, IL-6-targeted therapies, and supportive care are frequently used to manage patients with neurotoxicity.