Neurological immune-related adverse events and overall survival in patients with advanced solid tumors treated with immune checkpoint inhibitors in a global real-world analysis.

Abstract

11165 Background: Immune checkpoint inhibitors (ICIs) have transformed the treatment of advanced malignancies, and many immune-related adverse events have been associated with improved treatment outcomes. Neurological immune-related adverse events, however, are uncommon, often severe, and poorly characterized in large real-world populations. Whether the development of neurological toxicity during ICI therapy is associated with long-term survival remains unclear. We examined the relationship between neurological immune-related adverse events and overall survival in a large real-world cohort of patients treated with ICIs. Methods: We performed a retrospective cohort study using data from the TriNetX Global Collaborative Network. Adult patients with advanced solid tumors treated with immune checkpoint inhibitors, including pembrolizumab, nivolumab, ipilimumab, atezolizumab, or durvalumab, were identified. Patients who developed neurological immune-related adverse events (such as encephalitis, meningitis, Guillain–Barré syndrome, myasthenia gravis, or immune-mediated polyneuropathy) within six months of treatment initiation were compared with patients who did not experience neurological toxicity. One-to-one propensity score matching was used to balance age, sex, race, ethnicity, and major medical comorbidities. Overall survival was assessed in the matched cohorts. Results: After matching, 9,744 patients were included (4,872 per cohort) with well-balanced baseline characteristics. Patients who developed neurological immune-related adverse events experienced significantly worse overall survival compared with matched controls. Median overall survival was 473 days in the neurological toxicity cohort versus 1,083 days among patients without neurological events (p < 0.001). Development of neurological immune-related adverse events was associated with a 57% higher risk of death (hazard ratio 1.57; 95% CI, 1.48–1.67). At five years, survival probability was 30.9% in the neurological toxicity group compared with 41.7% in the control group. Conclusions: In this large real-world analysis, neurological immune-related adverse events were associated with substantially worse overall survival in patients treated with immune checkpoint inhibitors. In contrast to other immune-related toxicities that may reflect effective immune activation, neurological complications appear to confer significant morbidity and mortality that outweigh potential treatment benefit. These findings highlight the need for early recognition, multidisciplinary management, and careful risk–benefit assessment when neurological toxicity develops during immunotherapy.