Acute Neurotoxicity Syndromes from Immunotherapy: Emergency and ICU Management

Advances in cancer immunotherapy have transformed survival outcomes and driven widespread adoption of these treatments. However, as the population receiving immunotherapy has grown, neurologic complications have increasingly emerged, with rates of 1 to 3% among patients receiving immune checkpoint inhibitors and 26.9% among chimeric antigen receptor (CAR) T cell therapy recipients across all FDA-approved products. This review focuses on the early recognition and acute management of neurologic toxicities associated with immunotherapy, with particular emphasis on immune effector cell–associated neurotoxicity syndrome (ICANS) related to CD19 and BCMA-directed CAR T cell therapies. Herein we synthesize current understanding of clinical phenotypes and risk factors for severe neurotoxicity, and review evidence-based approaches to diagnostic evaluation, including neuroimaging, electroencephalography, and laboratory markers. Practical management strategies for severe cases are discussed, including corticosteroid initiation, cytokine-directed immunomodulatory therapies, exploratory therapies, and neurocritical supportive care for fulminant cerebral edema and status epilepticus. We address less common but high-risk neurologic complications associated with CAR T cell therapy beyond ICANS. Lastly, we touch upon key clinical findings and treatments for acute neurologic complications related to immune checkpoint inhibitors, bispecific T cell engagers, tumor-infiltrating lymphocyte therapy, and engineered T cell receptor therapies.