Neurotoxicity associated with cancer immunotherapy: immune checkpoint inhibitors and chimeric antigen receptor T-cell...

Immune checkpoint inhibitors (ICPI) and chimeric antigen receptor T cells (CAR-T) represent novel therapies recently approved to treat a number of human cancers. As both approaches modulate the immune system, they can generate a number of immune-related adverse events (irAEs), including a large spectrum of novel neurological toxicities. These are of special interest given their potential severity and risk of compromising further oncologic treatment. We aim to provide a comprehensive review of the literature and discuss their optimal management.

In contrast to irAEs involving other organs, neurological complications of ICPI are uncommon, may present throughout the course of treatment and involve the peripheral and central nervous system, including polyneuropathy, myositis, myasthenia gravis, demyelinating polyradiculopathy, myelitis, encephalitis and others. If started early, ICPI-related neurologic irAEs are usually responsive to steroids. In contrast, as many as 40% of patients undergoing CAR-T therapy will develop neurologic complications in the form of a cytokine-release-associated encephalopathy. It includes delirium, aphasia, tremor/myoclonus, seizure and seizure-like activity.

irAEs associated with CAR-T and ICPI therapy constitute new entities. Early identification and treatment are essential to optimize the functional outcome and further oncologic management of the patient.