MMAP-10 ADVERSE RADIATION EFFECT AFTER STEREOTACTIC RADIOSURGERY AND IMMUNOTHERAPY/TARGETED THERAPY FOR MELANOMA BRAIN METASTASES

BACKGROUND: Safety of immunotherapy (IO) and targeted therapy (TT) with stereotactic radiosurgery (SRS) in melanoma brain metastases (MBM) treatment remains incompletely understood. We aim to identify whether timing of IO/TT in relation to SRS impacts rates of adverse radiation effect (ARE) in MBM. METHODS: Retrospective review of patients with MBM treated with SRS and IO/TT within three months prior and one year after SRS, from 2011-2021 at a single institution with at least two months MRI follow-up, identified 108 patients with 939 unique MBM meeting criteria. ARE was confirmed on independent imaging review. Concurrent IO/TT was defined as receiving IO/TT within 4 weeks before or after SRS. Data analysis was performed with the univariate cox proportional hazard model and Kaplan-Meier method. RESULTS: Median radiographic follow-up from time of SRS was 16months. IO/TT was initiated prior to SRS for 681 (72.5%) metastases and after SRS for 258 (27.5%) metastases. 837 (89.1%) metastases received concurrent IO/TT. Most common IO agents were ipilimumab (n=416), nivolumab (n=448), and pembrolizumab (n=203). Most common TT agents were dabrafenib (n=548), trametinib (n=540), and vemurafenib (n=81). 2-year local progression-free survival (PFS), distant intracranial PFS, and overall survival were 94.1%, 33.3%, and 55.2%, respectively. 55 (5.9%) metastases in 33 (30.6%) patients experienced ARE. Median time to ARE was 5mo (IQR 4-9mo). Of those who experienced ARE, 22 (66.7%) patients were symptomatic and treated with steroids; 12 (36.4%) patients underwent surgical intervention. ARE rates were not impacted by concurrent vs nonconcurrent IO/TT (5.5% vs 4.9%, p=0.34) nor IO/TT initiation pre vs post SRS (6.0% vs 5.4%, p=0.61). CONCLUSION: IO/TT in conjunction with SRS resulted in low ARE rates as compared to historical controls in the pre-IO/TT era. Timing of IO/TT in relation to SRS may not significantly impact ARE rates in MBM treatment.