Impact of immunotherapy on prevalence of brain metastases in malignant melanoma: a realworld population-level analysis

Abstract INTRODUCTION Melanoma brain metastases (MBM) are often associated with poor prognosis. Over the last decade, the treatment paradigm for malignant melanoma shifted with the introduction of immunotherapies (ITs), including ipilimumab (ipi) and nivolumab (nivo). Recent clinical trials suggest that IT offers a survival benefit in MBM and may suffice as the sole intervention in those with small, asymptomatic lesions. Secondary trial analyses suggest IT may reduce rates of BM. The goal of this study was to assess the potential impact of IT in reducing prevalence of MBM in a real-world population-level analysis. METHODS A retrospective query of TriNetX, a database that collates clinical data from 92 healthcare organizations, was performed. Melanoma patients without brain metastases at diagnosis were stratified as: 1) ipi and nivo (dual-IT), 2) ipi alone (single-IT), or 3) no IT treatment (no-IT). A new diagnosis of MBM, from one month of initiating IT to any time after, was compared among cohorts. Median overall survival (OS) of MBM patients were calculated and compared using Kaplan Meier analysis and log-rank tests. RESULTS 732,555 melanoma patients were included (717,408 no IT, 4,585 dual-IT, 4,101 single-IT). Mean ages at MBM diagnosis were 66.9, 61.5, and 63.2 years, respectively. MBM prevalence was 1.5%, 9.6%, and 15.6%, for the respective cohorts (p < 0.0001). Dual-IT was associated with a lower rate of MBM compared to single-IT (OR [95%CI], 0.64 [0.61-0.77]). After propensity score matching for age, sex, and comorbidities, median OS were not statistically different between the no-IT, dual-IT, and single-IT cohorts (347, 400, 414 days) for MBM patients. CONCLUSION This analysis of real-world data suggests that dual-IT for malignant melanomas decreased the incidence of MBMs compared to single-IT. However, survival outcomes remain comparable once patients succumb to the MBM diagnosis. Prospective studies are underway to look at MBM prevalence given various dual-IT.