Neurological immune-related adverse events of immune checkpoint inhibitors: clinical and hematological risk factors

Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, but can induce neurological immune-related adverse events (n-irAEs). Objective: We aimed at evaluating the occurrence and characteristics of n-irAEs in cancer patients treated with ICIs and identifying biomarkers predictive of such complications in a single-center case–control study in the USA. Methods: We retrospectively reviewed the electronic health records for all patients treated with ICIs at the University of Cincinnati in 2011–2023. Demographic and clinical data were gathered for patients who experienced at least one n-irAE. Logistic regression was conducted to assess the associated factors for n-irAEs. Results: Twenty-eight (1.5%)/1817 patients who received ICI developed n-irAEs. Compared to those who did not, n-irAEs patients were older (median age, 75 vs 68 years; p < 0.001), male (75%, vs 56% p = 0.04), more likely to have used more than one ICI drug (36% vs 15%, p = 0.015), and had higher absolute eosinophil count before the first infusion (159 [75–251] vs 94 [37–194] cells/uL, p = 0.039). The most common cancer site was melanoma among cases (43%) and lungs in controls (31%, p < 0.001; non-small cell lung cancer, 73%). Neuropathy (34.4%) and encephalitis (18.8%) were the most common n-irAEs. Three subjects died of n-irAEs complications. Sixteen/28 cases (57%) improved at follow-up after ICIs discontinuation. The median time to n-irAEs after ICI administration was 68 (30–473) days. Conclusion: N-irAEs are rare, serious, and potentially reversible complications of ICIs, occurring in the early treatment phase. Older age, male sex, multiple ICI therapies, and higher absolute eosinophil count before first infusion are associated with n-irAEs.