Patients with cancer have a lower risk of developing neurologic adverse events (NAEs) when treated with immune checkpoint inhibitors (ICIs) than when treated with chemotherapy and other drugs, according to research published in JAMA Network Open.

The risk of NAEs overall, as well as the risks of peripheral neuropathy, paresthesia, and dysgeusia, were lower with ICIs than with chemotherapy across a range of malignancies. 

To assess the risk of NAEs, researchers performed a review and meta-analysis, pooling data from 39 randomized controlled trials involving ICIs for the treatment of cancer. Cancer types included lung cancer, melanoma, multiple myeloma, head and neck cancer, gastrointestinal cancers, genitourinary cancers, and mesothelioma. 

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The analysis included a total of 23,705 patients — 10,595 who received ICIs and 13,110 who received control treatments. Control treatments included other active drug regimens (chemotherapy, targeted therapies, vaccines, and combination therapies) as well as placebo.

The risk of NAEs was 41% lower in patients treated with ICIs than in patients who received another drug regimen or a placebo (risk ratio [RR], 0.59; 95% CI, 0.45-0.77). 

With respect to specific NAEs, patients treated with ICIs had a significantly lower risk of developing peripheral neuropathy (RR, 0.30; 95% CI, 0.17-0.51) and dysgeusia (RR, 0.41; 95% CI, 0.27-0.63). However, ICIs were more commonly associated with headache (RR, 1.32; 95% CI, 1.10-1.59).

Relative to counterparts treated with chemotherapy, patients treated with ICIs had a significant reduction in the risk of NAEs overall (RR, 0.22; 95% CI, 0.13-0.39). In particular, patients treated with ICIs were less likely to develop peripheral neuropathy (RR, 0.09; 95% CI, 0.05-0.17), dysgeusia (RR, 0.42; 95% CI, 0.21-0.85), and paresthesia (RR, 0.29; 95% CI, 0.13-0.67).

In the trials designed to compare ICI therapy with placebo, the overall risk of NAEs was significantly higher among patients treated with ICIs (RR, 1.57; 95% CI, 1.30-1.89). In particular, ICIs were associated with a higher risk of headache (RR, 1.63; 95%, CI, 1.32-2.02).

The researchers emphasized the need for additional research to understand the full spectrum of NAEs associated with the use of ICIs, especially the rare events not well captured in trials.

Still, according to a related editorial, this study “serves to help us more clearly determine the risks to which we are exposing our patients during treatment with ICIs and to offer more data for our discussions of risk vs benefits with our patients.”2

Disclosures: One study author and the editorial author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


1. Farooq MZ, Aqeel SB, Lingamaneni P, et al. Association of immune checkpoint inhibitors with neurologic adverse events: A systematic review and meta-analysis. JAMA Netw Open. 2022;5(4):e227722. doi:10.1001/jamanetworkopen.2022.7722

2. Vargas Pivato de Almeida D. Neurological toxic effects associated with treatment with immune checkpoint inhibitors—are we really safer now? JAMA Netw Open. 2022;5(4):e227731. doi:10.1001/jamanetworkopen.2022.7731