Central nervous system injury from novel cancer immunotherapies

Neurotoxicity from antineoplastic treatment remains a challenge in oncology. Cancer treatment-induced central nervous system (CNS) injury can be therapy-limiting, severely disabling, and even fatal. While emerging cancer immunotherapies have revolutionized oncology during the past decade, their immunomodulatory properties can cause immune-related adverse effects (IRAE) across organ systems, including the nervous system. Central neurologic IRAEs from chimeric antigen receptor T cells (CAR-T) and immune checkpoint inhibitors (ICPI) are challenging complications of such therapies.We aim to provide clinicians with a comprehensive review of the relevant forms of CAR-T and ICPI-associated CNS toxicity, focusing on clinical features of such complications, diagnostic workup, predictive biomarkers, and management considerations in affected patients.

Unique forms of CAR-T and ICPI-related CNS toxicity have been characterized in the recent literature. CAR-T-related neurotoxicity is common and clinically well delineated. ICPI-related CNS toxicity is relatively rare but includes a heterogenous spectrum of severe and diagnostically challenging conditions. While putative risk factors, neurotoxicity biomarkers, imaging correlates and treatment strategies have been put forward, development of tailored diagnostic and management consensus guidelines awaits further clinical investigation.

As CAR-T and ICPI become more widely adopted, early recognition, documentation, and management of immunotherapy-related CNS toxicity are of paramount importance in the clinical setting.