BM-05 * IPILUMUMAB THERAPY FOR MELANOMA BRAIN METASTASES IS ASSOCIATED WITH INCREASED RADIATION NECROSIS

Abstract

BACKGROUND: Melanoma brain metastases (MBMs) are typically associated with poor prognosis, requiring combination therapy with surgery and radiation. The CTLA-4 antagonist, ipilumumab, has shown improved survival in patients with MBMs. Herein, we present a series of patients treated with variable combinations of radiation, surgery and ipilumumab. METHODS: Over 4.5 years, all patients with symptomatic MBMs with at least one craniotomy for tumor resection and radiation therapy were included. The onset, duration and magnitude of radiation necrosis (RN) were analyzed relative to surgical resection, tumor size, and ipilumumab therapy. RN was based on pathology or imaging findings. Patients with less than 6 months follow-up were excluded. RESULTS: The cohort consisted of 59 patients (42 males, 17 females, age 58 ± 14 years) with 154 metastatic tumors. 48 patients (81.4%) underwent adjuvant radiation therapy (74.6% SRS, 22% WBRT). A total of 68 MBMs were resected in these patients (27.3 ± 11.6mm max dimension). Median overall and progression-free survival was 10.5 and 6.8 months respectively. 72% received ipilumumab therapy. Lesions receiving both SRS and WBRT had increased risk of RN compared to SRS or WBRT alone (38.5%v13.1%v9.1%, p = 0.003). Ipilumumab therapy was associated with increased RN (20.7%v4.7%, p = 0.015). Lesions that received ipilumumab following radiation were at higher risk of developing RN compared to ipilumumab preceding radiation (26.0%v16.4%, p = 0.023) with treatment interval 2.5v3.8 months. Overall, there was no significant difference in tumor size and rate of RN (28.2 ± 11.8v22.7± 12.2mm, p = 0.071). However, in patients who did not receive ipilumumab therapy, tumor size was significantly associated with RN (28.2 ± 11.8v19.2 ± 9.1mm, p = 0.010). Multivariate analysis demonstrated SRS in the absence of ipilumumab as an independent factor for RN. Surgical resection prior to radiation did not reduce RN rate (15.9%v23.7%, p = 0.312). CONCLUSION: This series demonstrates that ipilumumab independently increases the risk of RN for MBMs, particularly with SRS. Paradoxically, ipilumumab therapy following radiation had a higher rate of RN, suggesting an ongoing immune-mediated process in the radiated field.