834P Intracranial disease control and survival in patients with melanoma brain metastases (MBM) treated with radiation and immune checkpoint inhibitors (IO)

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Combination immunotherapy with anti-PD1/CTLA4 is the standard for patients (pts) with MBM with the highest potential of long-term control. However, the utility of immunotherapy (IO) in delaying intracranial (IC) progression in pts with radiated MBM remains unexplored. This retrospective study assessed pts with MBM who received radiation therapy (RT) followed by IO. Primary endpoints were overall survival (OS) and IC progression-free survival (IC-PFS), defined as the time from IO initiation to investigator-assessed IC progression or death. In pts who received IO following IC progression, we assessed the time from IO re-initiation to subsequent IC progression (second IC-PFS). Survival analyses were obtained using Log-Rank and Cox regression was applied to detect differences in specified subgroups. A p-value < 0.05 was statistically significant. 101 pts with MBM received IO after RT between 2010-2021. Median age was 58 (19-87) years; 60 (59%) were male. Skin and unknown primary melanomas comprised 66 (65%) and 18 (18%) pts, respectively. Molecular studies were available for 79 pts and 42 (53%) had BRAF V600 mutations. At MBM diagnosis, 30 (30%) pts had > 3 brain lesions, 42 (42%) presented neurologic symptoms, and 27 (27%) had prior IO. Ninety-three (92%) pts had SRS, and 52 (52%) had IO in the first line metastatic setting. Following MBM diagnosis, 29 (29%) pts received anti-PD1, and 33 (33%) anti-PD1+CTLA4. Median follow up was 43.1 (0.8-107.9) months (mo), median OS was 18.1 mo (95% CI 11.3-24.8), and median IC-PFS was 8.9 mo (95% CI 4.1-13.7). Anti-PD1-based therapy favourably impacted OS and IC-PFS (Table). Among 22 pts who received IO after IC progression, median OS following IO resumption was 16 mo (95% CI 7.5-24.5). and median second IC-PFS was 11.3 mo (95% CI 0.3-22.9).Table: 834PIC-PFS: HR (95% CI); POS: HR (95% CI); PAnti-CTLA411Anti-PD1+CTLA40.27 (0.15-0.48); < 0.0010.25 (0.13-0.48); < 0.001Anti-PD10.33 (0.18-0.59); < 0.0010.32 (0.17-0.58); < 0.001Anti-PD1+other0.34 (0.12-0.99); 0.040.60 (0.23-1.57); 0.3 Open table in a new tab This data corroborates the activity of anti-PD1-based IO for pts with treated MBM and suggests ongoing IC activity beyond progression.