NCMP-07. ADVERSE NEUROLOGIC COMPLICATIONS FOLLOWING IMMUNE CHECKPOINT INHIBITORS FOR TREATMENT OF MELANOMA: COMPARATIVE ANALYSIS OF PD-1 INHIBITOR MONOTHERAPY TO COMBINATION THERAPY WITH CTLA-4 INHIBITORS

Abstract In the past decade, FDA approval of several novel immune checkpoint inhibitors (ICI) has revolutionized treatment of advanced melanoma. However, severe immune-related adverse events (irAEs) from these medications have been reported. This study examines whether PD-1/CTLA-4 inhibitor combination immunotherapy confers increased incidence of neurologic irAEs in melanoma patients compared to PD-1 inhibitor monotherapy. A retrospective, multicenter cohort study performed using TriNetX research platform identified adult patients diagnosed with melanoma. Cohort 1 (n=9,105) included melanoma patients treated with PD-1 inhibitor monotherapy (pembrolizumab or nivolumab). Cohort 2 (n=4,727) included melanoma patients treated with PD-1/CTLA-4 inhibitor combination therapy (PD-1 inhibitor + ipilimumab). Propensity Score Matching generated final cohorts (n=4,667) using covariates: gender, race, age at diagnosis, and history of nervous system disorders. Odds ratios (OR) were determined for the occurrence of neurologic irAEs at 3 years and 5 years following therapy initiation. Kaplan Meier analysis estimated survival probabilities for each irAE subtype, as defined by the 2021 Neuro irAE Disease Definition Panel. At 3 years post-diagnosis, there was increased risk of meningitis [OR: 2.8, 95% CI: (1.8, 4.2)], encephalitis [OR: 3.1, 95% CI: (1.9, 5.1)], demyelinating syndromes [OR: 2.7, 95% CI: (1.4, 5.2)], vasculitis [OR: 1.2, 95% CI: (0.5, 2.8)], peripheral neuropathy [OR: 1.3, 95% CI (1.1, 1.5)], neuromuscular junction disorders [OR: 1.1, 95% CI: (0.7, 1.8)], and myopathy [OR: 1.4, 95% CI: (1.1, 1.9)] in melanoma patients receiving combination immunotherapy compared to those receiving anti-PD-1 monotherapy. Increased incidence of neurologic irAEs corresponded with marginally lower, yet statistically significant decreases in survival probability (p<0.01), except for vasculitis (p=0.2) and neuromuscular junction irAEs (p=0.3). At 5 years following therapy initiation, these trends persisted. Melanoma patients receiving anti-PD-1/CTLA-4 combination therapies are at greater risk of neurologic irAEs than patients on anti-PD-1 monotherapy. Incidence of neurologic irAEs may confer worsened survival prognosis for these patients.