November 2023
Neurological immune-related adverse events with immune checkpoint inhibitor therapy for melanoma

Development of a neurological immune-related adverse event was associated with longer survival.

Therapy with immune checkpoint inhibitors has revolutionised the treatment a wide variety of cancers, including melanoma. However, immune checkpoint inhibitors have been associated with a variety of immune-related adverse events (irAEs), including those of the nervous system (nirAEs; NEJM JW Neurol 2017 Oct 31 and JAMA Neurol 2017; 74: 1216-1222 and Neurology 2017; 89: 1127-1134). To explore the association of patient age with development of a nirAE and the association of nirAEs with survival out-comes, researchers in Israel performed a retrospective, single-centre study of patients treated with immune check-point inhibitor therapy for melanoma over a seven-year period.

Among 937 immune checkpoint inhibitor-treated patients, 76 (8%) developed a nirAE, most commonly myositis (40% of nirAEs), encephalitis (11%) and neuropathy (11%). Patient age was not associated with nirAE occurrence. Among nirAE patients, 40% required hospitalisation. However, only 46% of nirAE patients required corticosteroid treatment, and nine of these patients needed additional immunosuppressive treatment. Immune checkpoint inhibitor therapy was resumed in 18% of nirAE patients, and 29% of these patients experienced another nirAE. Patients who developed a nirAE had significantly higher overall survival (hazard ratio for death, 0.497; 95% confidence interval, 0.32–0.77) than those who developed no irAE. Only one patient’s death was due to a nirAE (myasthenia). 

Comment: This series demonstrates that, in patients with melanoma treated with immune checkpoint inhibitors, neurological immune-related adverse events are frequent but do not reduce overall survival. In fact, the development of a nirAE is associated with higher overall survival, potentially indicative of a robust ICI-induced immune response. Further research is needed to better identify patients at particular risk for nirAEs and those who would benefit from immune checkpoint inhibitor rechallenge. From the limited data here, immune checkpoint inhibitor rechallenge with close clinical monitoring seems a reasonable consideration.

Note to readers: At the time we reviewed this paper, its publisher noted that it was not in final form and that subsequent changes might be made.

John C. Probasco, MD, Professor, Department of Neurology, and Director, Division of Advanced Clinical Neurology, Johns Hopkins University School of Medicine, Baltimore, USA.

Pepys J, et al. Incidence and outcome of neurologic immune-related adverse events associated with immune checkpoint inhibitors in patients with melanoma. Neurology 2023 Aug 31; e-pub (https://

This summary is taken from the following Journal Watch title: Neurology.