Neurological complications of immune checkpoint inhibitors: a practical guide

Immune checkpoint inhibition unleashes the power of the immune system against tumour cells. Immune checkpoint inhibitors (ICIs) block the inhibitory effects of cytotoxic T-lymphocyte associated protein 4 (CTLA-4), programmed death protein 1 (PD-1), programmed death ligand 1 (PD-L1) and lymphocyte activation gene 3 (LAG-3) molecules on T-cells, and so enhance physiological cytotoxic effects. ICIs can significantly improve survival from cancers, including those previously associated with poor treatment response, such as metastatic melanoma. However, on-target off-tumour effects of ICIs result in immune-related adverse events. These toxicities are common and require new multidisciplinary expertise to manage. ICI neurotoxicity is relatively rare but ominous due to its severity, heterogenous manifestations and potential for long-term disability. Neurotoxic syndromes are novel and often present precipitously. Here, we describe ICI mechanisms of action, their impact on cancer outcomes and their frequency of immune-related adverse events. We focus particularly on neurotoxicity. We discuss the current appreciation of neurotoxic syndromes, management strategies and outcomes based on clinical expertise and consensus, multi-specialty guidance. The use of immunotherapy is expanding exponentially across multiple cancer types and so too will our approach to these cases.