{"doi":"10.1093/noajnl/vdaf030","title":"Adverse neurologic events of immune checkpoint inhibitor monotherapy vs. combination therapy for melanoma","abstract":"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.","journal":"Neuro-Oncology Advances","year":2025,"id":531927,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9521,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1320757,"name":"Ravi Dhamija","orcid":"0009-0000-7700-8121","position":1,"is_corresponding":false},{"id":109146,"name":"David C. Kaelber","orcid":"0000-0001-7855-9515","position":2,"is_corresponding":false},{"id":730052,"name":"Michael L. Kelly","orcid":"0000-0003-3421-4026","position":3,"is_corresponding":false},{"id":1412712,"name":"Peter Xie","orcid":"0000-0002-1635-5856","position":4,"is_corresponding":false},{"id":1413180,"name":"Deven Reddy","orcid":null,"position":5,"is_corresponding":false},{"id":1320758,"name":"Nikita Das","orcid":"0000-0002-0544-866X","position":0,"is_corresponding":true}],"reference_count":36,"raw_metadata":null,"created_at":"2026-07-19T02:51:18.928280Z","pmid":"40351833","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}