Unravelling the Acute, Chronic and Steroid-Refractory Management of High-Grade Neurological Immune-Related Adverse Events: A Call to Action

Rare side effects of immune-checkpoint inhibitors (ICIs) are known as neurological immune-related adverse events (n-irAEs). Typically, n-irAEs affect the peripheral nervous system, primarily presenting as myositis, polyradiculoneuropathy, or cranial neuropathy. Less commonly, they impact the central nervous system, resulting in encephalitis, meningitis, or myelitis. High-grade n-irAEs managing and recognizing remains challenging, considering the risk of mortality and long-term disability. To date, strong scientific data are lacking to support the management of high-grade clinical forms. We performed a systematic literature search, selecting all articles describing high-grade steroid-resistance n-irAEs. and we reported them in a practical review. Specifically, current recommendations advise stopping ICI use and beginning corticosteroid treatment. Our findings highlighted that in steroid-resistant n-irAEs, it should be recommended to quickly escalate to plasma exchange (PLEX) and/or intravenously immunoglobulins (IVIg), usually in association with other immunosuppressants. Furthermore, newer evidence supports the use of drugs that may specifically block inflammation without reducing the anti-tumour effect of ICIs. In this practical review, we provide new evidence regarding the therapeutic approach of high-grade n-irAEs, particularly in steroid-resistant cases. We would also stress the importance of informing the scientific community of the discrepancy between current guidelines and clinical evidence in these rare forms of pathology.