Immune-related adverse events and immune checkpoint inhibitors: a focus on neurotoxicity and clinical management

Immune checkpoint inhibitors (ICIs) represent an innovative therapeutic approach of oncologic diseases. In Europe, this therapeutic class currently includes eight agents: ipilimumab, pembrolizumab, nivolumab, atezolizumab, avelumab, cemiplimab, durvalumab and dostarlimab. Despite their proved clinical benefits, they can induce immune-related adverse events (irADRs), that can also involve the nervous system.

Despite their rarity, neurological irADRs related to ICI-treatments can lead to serious and dangerous complications, highlighting the importance of a strict monitoring of patients. This review aims to summarize the safety profile of ICIs, focusing on their possible neurotoxicity and their management.

Considering the clinical relevance of ICIs-induced irADRs and that the underlying mechanisms are still not completely understood, the use of ICIs requires extensive safety monitoring. Before to prescribe immunotherapy, oncologists should identify possible individual risk factors that may favor the onset of irADRs. Oncologists and general practitioners should inform and educate patients about the specific toxicities of immunological checkpoint inhibitors, including nervous ones. They should be carefully monitored at least 6 months after the end of treatment. ICIs-related nervous toxicities require a multidisciplinary management, in which neurologists and clinical pharmacologists should participate.