NCOG-47. Real-world impact of immunotherapy on survival in melanoma patients with brain metastases: a population-based study in the United States

Abstract BACKGROUND Melanoma brain metastases (MBM) are associated with high mortality. While immunotherapy has become a standard of care in melanoma, its real-world impact on survival in patients with brain involvement remains less studied. METHODS We identified 7,252 patients with MBM diagnosed between 2015 and 2021 from the National Cancer Database. Patients were stratified by receipt of immunotherapy. Overall survival (OS) was analyzed using Kaplan-Meier estimates and Cox proportional hazards models. Multivariable models were adjusted for demographic, clinical, socioeconomic, geographic, and facility-level characteristics. Subgroup analyses assessed consistency of treatment effects across patient and system factors. RESULTS Among 7,252 patients with MBM, 3,759 (52%) received immunotherapy. Median OS was markedly longer in patients treated with immunotherapy (15.8 months, 95% CI: 14.2-17.3) compared to non-recipients (3.6 months, 95% CI: 3.4-3.8). One-year survival was 54.5% in the immunotherapy group versus 24.6% in the untreated group, and 3-year survival was 37.3% versus 14.0%, respectively. In multivariable Cox regression, immunotherapy was associated with a 55% reduction in mortality (HR: 0.45, 95% CI: 0.42-0.47, P<0.001). The benefit was consistent across clinical and sociodemographic subgroups, including age, comorbidity level, income, and facility type. Independent predictors of improved survival included female sex (HR: 0.93, P=0.019), treatment at academic centers (HR: 0.74, P<0.001), and longer travel distance to care (>50 miles: HR: 0.81, P<0.001). Worse survival was associated with older age (≥65 years: HR: 2.02 vs. 18-39, P<0.001), and greater comorbidity burden (Charlson-Deyo score 2-3: HR: 1.32, p<0.001). Median income range ($46,277-57,858) was associated with slightly increased mortality (HR: 1.28, p=<0.001), vs. lower income group (<$46,276). CONCLUSIONS Immunotherapy is strongly associated with significantly improved survival in patients with MBM. These findings provide real-world validation of -its benefit seen in clinical trials.