# Toxicity profiles of immune checkpoint inhibitors in nervous system cancer: a comprehensive disproportionality analysis using FDA adverse event reporting system

## TL;DR

This study examines the side effects of immune checkpoint inhibitors in nervous system cancer patients, identifying common adverse events and their potential molecular causes.

## Contribution

The study provides a comprehensive analysis of immune-related adverse events in nervous system cancer patients using FDA data and molecular mechanisms from the GEO database.

## Key findings

- Fourteen immune-related adverse events were identified, with seizure, confused state, encephalopathy, muscular weakness, and gait disturbance being the most common.
- Older patients were more likely to develop adverse events and showed differences in the time to onset compared to younger patients.
- Potential mechanisms for adverse events include inflammatory responses and aberrant activation of pathologic pathways.

## Abstract

Background: Immune-related adverse events (irAEs) always occur during treatment with immune checkpoint inhibitors (ICIs). Patients with nervous system cancer (NSC) may gain clinical benefit from ICIs, but irAEs in NSC patients are rarely examined. Therefore, our study systematically summarized reports of irAEs in NSC. Methods: We obtained information from the FDA adverse event reporting system from the first quarter (Q1) of 2013 to the fourth quarter (Q4) of 2022. We examined use of a combination of ICIs and chemotherapy (ICI_Chemo) or chemotherapy only (ICI_Chemo) for patients with NSC. Multiple disproportionality analyses were applied to assess irAEs. Multiomics data from the gene expression omnibus (GEO) database were analyzed to explore potential molecular mechanisms associated with irAEs in NSC patients. Results: Fourteen irAEs were identified in 8,357 NSC patients after removing duplicates; the top five events were seizure, confused state, encephalopathy, muscular weakness and gait disturbance. Older patients were more likely to develop irAEs than were younger patients. From the start of ICIs_Chemo to irAE occurrence, there was a significant difference in the time to onset of irAEs between age groups. irAEs may occur via mechanisms involving the inflammatory response, secretion of inflammatory mediators, and aberrant activation of pathologic pathways. Conclusions: This study helps to characterize irAEs in NSC patients treated with ICIs. We combined GEO database analysis to explore the potential molecular mechanisms of irAEs. The results of this study provide a basis for improving the toxic effects of ICIs in NSC patients.

The online version contains supplementary material available at 10.1007/s10238-024-01403-2.