Imun-07 Timing and Outcome of Brain Metastases Following First-Line Ipilimumab Plus Nivolumab Therapy for Metastatic Melanoma in a Community Oncology Practice

Abstract Melanoma brain metastases (MBM) are a frequent complication of advanced stage disease. MBM are an important cause of morbidity and mortality during disease progression. We report a retrospective cohort study of patients treated with combined ipilimumab and nivolumab as initial therapy for metastatic melanoma to identify and evaluate the clinical course of patients who developed brain metastases in the “real world setting.” The aim of our study was (1) to determine the frequency and timing of brain metastases onset and (2) to characterize the incidence and timing of brain metastases following first line combined ipilimumab-nivolumab therapy. We evaluated 73 patients. Only 20 (27.4%) patients developed MBM. The majority of these patients were identified at initial evaluation of metastatic disease (20.5%), while the rate of CNS progression during immunotherapy was low (6.9%). Patient treatment response, progression-free survival (PFS), overall survival, and neurologic progression-free survival (CNS PFS) were evaluated. We observed that patients with MBM at diagnosis of metastatic disease had improved PFS and CNS PFS, compared to patients who progressed in the CNS following treatment. Despite the presence of symptomatic MBM at diagnosis, 27% of patients with MBM at diagnosis achieved a durable complete remission (NED). Of note, all responding patients presented with neurologic symptoms associated with their brain metastases, and half of them were receiving systemic steroids at the time of treatment. In contrast, patients with delayed onset of brain metastases had an extremely poor outcome, with a median PFS of only 4.8 months. Thus, in patients presenting with MBM at diagnosis of metastatic disease, combined ipilimumab/nivolumab therapy has significant clinical activity. Furthermore, checkpoint inhibitor therapy appears to reduce the frequency of delayed onset brain metastases. However, novel treatment options need to be developed to more effectively treat patients who progress in the CNS following initial combination therapy.