Neurological adverse events related to immune checkpoint inhibitors in cancer treatment: A systematic review and meta-analysis of clinical trials.

e14569 Background: Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment with significant improvements in survival and recurrence rates among several cancer types. However, their increasing use was accompanied by several case reports and series describing their neurological adverse events. We conducted this systematic review and meta-analysis to estimate the prevalence of neurological adverse events (NAEs) among ICI clinical trials. Methods: We searched PubMed, Embase, Scopus, and Cochrane Central Register of Controlled Trials (CENTRAL) on 11/25/2025 using ICI and clinical trial as keywords along with their related MeSH terms. The inclusion criteria involved clinical trials investigating the efficacy or safety of any ICI as the only systemic therapy among never treated patients with cancer. To eliminate the impact of other systemic therapy, trials that used ICI as an adjuvant to another systemic treatment or included patients previously treated with any systemic therapy other than ICI were excluded. Prevalence of NAEs and 95% confidence intervals (95%CI) were used as the effect measures in the analysis. Subgroup analyses were performed by type of cancer and number of ICIs used in the trial. Results: We included a total of 8,826 patients with cancer from 31 clinical trials. The pooled prevalence of neurological adverse events was 1.78 ×10 -3 % (95%CI: 1.06×10 -3 %-2.78 ×10 -3 %). There was no significant difference in the prevalence of neurological side effects between trials that used one ICI (1.83×10 -3 % ; 95%CI: 0.81×10 -3 %-3.22 ×10 -3 %) compared to those that used two ICIs (0.90×10 -3 % ; 95%CI: 0.01×10 -3 %-2.64×10 -3 %). Furthermore, no significant difference was found in the prevalence among patients with hepatocellular carcinoma (1.20; 95%CI: 0.01-3.67), non-small cell lung carcinoma (1.83×10 -3 %; 95%CI: 0.01x10 -3 %-6.0×10 -3 %), or melanoma (1.16×10 -3 %; 95%CI: 0.22×10 -3 %-2.71×10 -3 %). The most common neurological adverse events were peripheral neuropathy (1.34×10 -3 %; 95%CI: 0.61 ×10 -3 %-2.3×10 -3 %), myositis (0.78 ×10 -3 %; 95%CI: 0.29×10 -3 %-1.49 ×10 -3 %), aseptic meningitis (0.71×10 -3 %; 95%CI: 0.25×10 -3 %-1.40×10 -3 %), autoimmune demyelinating polyneuropathy (0.66×10 -3 %; 95%CI: 0.21×10 -3 %-1.32×10 -3 %), epilepsy (0.66 ×10 -3 %; 95%CI: 0.21×10 -3 %-1.32×10 -3 %) and myasthenia gravis (0.66×10 -3 %; 95%CI: 0.21×10 -3 %-1.32×10 -3 %). Conclusions: All in all, the prevalence of ICI related neurological adverse events among patients with cancer is low and estimated at 1 in 5000 patients. Individual data analysis of ICI clinical trials is needed to elucidate the factors associated with ICI related neurological adverse events.