Neurological complications of chimeric antigen receptor T cells and immune-checkpoint inhibitors: ongoing challenges in daily practice

Purpose of review The aim of this review is to summarize the most recent advances in the management of neurological toxicities associated with immune-checkpoint inhibitors (ICIs) and chimeric antigen receptor (CAR)-T cells. Recent findings The advent of cancer immunotherapies has dramatically improved the prognosis of several refractory and advanced neoplasms. Owing to their mechanism of action, cancer immunotherapies have been associated with a variety of immune-related adverse events (irAE). Neurological irAE are uncommon compared with other irAE, but they are associated with significant morbidity and mortality. Despite the efforts to draft common protocols and guidelines, the management of neurological irAE remains challenging. Our ability to predict the development of neurotoxicity is still limited, hampering to elaborate prevention strategies. Treatment heavily relies on the administration of high-dose corticosteroids that, however, have the potential to impair oncological efficacy. The experimentation of novel strategies to avoid resorting to corticosteroids is hindered by the lack of an adequate understanding of the pathogenetic mechanisms driving the development of irAE. In this review, we will discuss the most recent advances on the diagnosis and management of neurological irAE associated with ICIs and CAR-T cells, focusing on the issues that remain most challenging in clinical practice.