Mmap-17 Management of Melanoma Brain Metastases With Ipilimumab and Nivolumab With or Without Upfront Comprehensive Stereotactic Radiosurgery

Abstract BACKGROUND The combination of ipilimumab and nivolumab (ipi/nivo) has been shown to have intracranial efficacy in well-selected patients with melanoma brain metastases (MBM). Questions remain regarding the indications for upfront versus deferred comprehensive stereotactic radiosurgery (cSRS) in this context. METHODS This single-institution retrospective study identified patients who started ipi/nivo for newly diagnosed MBM between 2018 and 2023 with or without upfront cSRS. Exclusionary criteria included prior whole brain radiotherapy, 15 MBM, or leptomeningeal disease. Clinical outcomes were compared using multivariable regression models and reported with adjusted hazard ratios (aHR) 95% confidence intervals. The first instance of intracranial progression was further categorized by the presence of local failure (enlargement of MBM) and/or distant failure (new MBM). RESULTS Of the 132 patients identified, 52.3% received upfront cSRS and 47.7% did not. Patients treated with upfront cSRS were more commonly characterized by larger brain metastases (median 2.3 cm vs. 0.7 cm; p0.001), symptomatic brain metastases (59.4% vs. 11.1%; p0.001), the absence of a BRAF V600 mutation (65.2% vs. 46.0%; p=0.035), and the use of upfront craniotomy (47.8% vs. 7.9%; p0.001). Median overall survival was 47.0 months for all patients, without significant improvement noted from upfront cSRS (aHR 1.01 0.60-1.68; p=0.98). However, upfront cSRS was associated with longer intracranial progression-free survival (median 16.8 vs. 5.5 mo; aHR 0.47 0.30-0.74; p=0.001). Local intracranial failure occurred less commonly for those treated with upfront cSRS (1.4% vs. 44.4%), though distant intracranial failure rates were similar (47.8% vs. 42.9%). Symptomatic radionecrosis from upfront SRS occurred in 18.1% of patients. CONCLUSIONS Patients with MBM started on ipi/nivo have good overall prognosis, but those managed with upfront cSRS tended to have higher risk features. Preservation of equivalent survival in this population highlights the effectiveness of cSRS in mitigating adverse features, in addition to reducing intracranial progression.