Neurooncol Adv. 2025 Feb 7;7(1):vdaf030. doi: 10.1093/noajnl/vdaf030. eCollection 2025 Jan-Dec.
ABSTRACT
BACKGROUND: Over the past decade, novel immune checkpoint inhibitors have revolutionized melanoma treatment. These new therapies are associated with complex immune-related adverse events. This study examines whether combination anti-PD-1/CTLA-4 immunotherapy for melanoma is associated with increased incidence of neurologic irAEs (n-irAEs) compared to anti-PD-1 monotherapy.
METHODS: A retrospective, multicenter study using TriNetX identified adult melanoma patients receiving anti-PD-1 monotherapy (pembrolizumab or nivolumab) (Cohort 1: n = 10,586) and patients receiving anti-PD-1/CTLA-4 combination therapy (nivolumab + ipilimumab) (Cohort 2: n = 5,705). Propensity score matching generated final cohorts (n = 5,185) using covariates: gender, race, age at diagnosis, TNM staging, nervous system metastasis, and history of neurologic disease. Odds ratios (OR) for n-irAE subtypes at 3- and 5-year post-therapy initiation were calculated, and Kaplan-Meier analyses assessed overall survival by aggregate n-irAE status in each cohort.
RESULTS: At 3 years, patients receiving combination immunotherapy exhibited increased risk of immune-related meningitis (OR: 2.6, 95% CI: [1.7, 4.1]) and encephalitis (OR: 3.0, 95% CI: [1.9, 4.9]), peripheral neuropathy (OR: 1.3, 95% CI [1.1, 1.5]), and myopathy (OR: 1.5, 95% CI: [1.1, 2.1]), but no significantly increased risk of demyelinating syndromes (OR: 1.5, 95% CI: [0.82, 2.6]), vasculitis (OR: 0.88, 95% CI: [0.43, 1.8]), or neuromuscular junction disorders (OR: 1.3, 95% CI: [0.87, 2.0]). At 5 years, these trends for risk of neurologic irAEs persisted. There was no significant difference in overall survival by n-irAE presence at 3 or 5 years in either cohort.
CONCLUSIONS: Melanoma patients receiving combination anti-PD-1/CTLA-4 immunotherapy have greater long-term risk of n-irAEs than patients receiving anti-PD-1 monotherapy.
PMID:40351833 | PMC:PMC12063080 | DOI:10.1093/noajnl/vdaf030
