Neurologic Toxicity of Immune Checkpoint Inhibitors: A Review of Literature.

Immune checkpoint inhibitors have entailed a change of paradigm in the management of multiple malignant diseases and are acquiring a key role in an increasing number of clinical sceneries. However, since their mechanism of action is not limited to the tumor microenvironment, their systemic activity may lead to a wide spectrum of immune-related side effects. Although neurological adverse events are much less frequent than gastrointestinal, hepatic, or lung toxicity, with an incidence of <5%, their potential severity and consequent interruptions to cancer treatment make them of particular importance. Despite them mainly implying peripheral neuropathies, immunotherapy has also been associated with an increased risk of encephalitis and paraneoplastic disorders affecting the central nervous system, often appearing in a clinical context where the appropriate diagnosis and early management of neuropsychiatric symptoms can be challenging. Although the pathogenesis of these complications is not fully understood yet, the blockade of tumoral inhibitory signals, and therefore the elicitation of cytotoxic T-cell-mediated response, seems to play a decisive role. The aim of this review was to summarize the current knowledge about the pathogenic mechanisms, clinical manifestations, and therapeutic recommendations regarding the main forms of neurotoxicity related to checkpoint inhibitors.
Competing Interests: CS travel and educational support: Novartis, Lilly, Pfizer, MSD, BMS. AS travel and educational support: MSD, BMS, and Pierre Fabre and has served as advisor and delivered lectures for Novartis, MSD, BMS, Sanofi Aventis, Pierre Fabre, and Merck Serono. PG travel and educational support: Pfizer, Ipsen, Sanofi-Genzyne, Roche, and Jansen and has served as advisor and delivered lectures for BMS, MSD, Merck Serono, Pfizer, Ipsen, Roche, Adacap, Eisai, Sanofi-Genzyme, Novartis, and Jansen. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2022 Albarrán, Chamorro, Rosero, Saavedra, Soria, Carrato and Gajate.)