RDTA-13 OUTCOMES AFTER SRS AND IPILIMUMAB/NIVOLUMAB FOR PATIENTS WITH MELANOMA BRAIN METASTASES WITH OR WITHOUT PRIOR CHECKPOINT EXPOSURE

Abstract While ipilimumab/nivolumab has demonstrated promising intracranial activity among patients with melanoma brain metastases (BM), patients with prior immune checkpoint inhibition (ICI) exposure may be at higher risk of worse intracranial disease control. We evaluated outcomes of patients with melanoma BM treated with ipilimumab/nivolumab and stereotactic radiosurgery (SRS) with or without prior ICI. Overall survival (OS) and intracranial progression-free survival (iPFS) were estimated from SRS using a non-parametric method, and Cox proportional hazards models were used to test clinically relevant factors. 64 consecutive patients with 393 treated BM between 2015 and 2024 were included with median follow-up of 20.2 months from SRS. 34 (53%) patients were alive at analysis. The 2-year OS and iPFS for the entire cohort was 52.1% and 36.4%, respectively. 32 patients (50%) had prior exposure to ICI. Performance status, age, number of BM, and receipt of surgery were not significantly different among patients with or without prior ICI. Patients with prior ICI had smaller BM (largest median diameter 19 mm vs 22.5 mm, p=0.022) and were less likely to have extracranial metastases (53.1% vs 78.1%, p=0.035). Patients with prior ICI exposure trended towards worse iPFS (median iPFS 4.3 months vs 13.5 months, p = 0.29) and had worse survival after SRS (median OS 17.6 months vs 50.5 months, p = 0.017). On univariate analysis, receipt of prior ICI (HR 2.16, 95% CI 1.13 – 4.11, p = 0.019), no upfront surgery (HR 0.38, 95% CI 0.20 – 0.72, p = 0.003), and number of treated BM (HR 1.04, 95% CI 1 – 1.08, p = 0.043) were significantly associated with OS. While ipilimumab/nivolumab with SRS demonstrates encouraging intracranial control, patients with prior ICI exposure are at higher risk of poor outcomes and may benefit from additional treatment strategies.