Incidence, patterns of progression and outcomes of melanoma brain metastasis (MBM) during programmed-death 1 inhibitor (PD1i) therapy.

Abstract

9532 Background: MBM are common in patients (pts) with metastatic melanoma (MM) and represent a frequent site of treatment failure with current therapies. Little is known, however, about the incidence, patterns of progression and outcomes of MBM pts treated with PD1i and in conjunction with central nervous system (CNS) focused therapy. Methods: Outcomes of mm pts treated with PD1i at MD Anderson from 01/12 to 07/16 were reviewed. The association between clinical variables and development of MBM and overall survival (OS) were assessed using logistic regression and Cox regression analyses. Results: We identified 324 mm pts, including 77 pts (24%) who had MBM prior to first dose of PD1i. Median follow-up from start of therapy was 16.3 months, median OS for pts without MBM at the start of PD1i 3.37 years, as compared to 2.85 years in pts with prior MBM (p = 0.268). Of the 247 pts without prior MBM, 64 (26%) developed MBM after exposure to PD1i. Of those, 21 pts (8.5%) developed MBM during therapy or within 30 days of discontinuation, with 12 (4.5%) having CNS-only progression, while 9 (3.6%) had both systemic and CNS progression. Pts with MBM prior to PD1i (n = 77) had CNS-only progression in 22 pts (28.6%) during therapy. Progression occurred in systemic and systemic plus CNS in 12 pts (15.6%) and 19 pts (24.7%), respectively. 24 pts (31.2%) had stable disease (SD). On multivariate analysis, pts with lung metastases (OR, 2.16; 95% CI, 1.25 - 3.78; p = 0.006) and NRAS-mutated tumors (OR, 2.17; 95% CI, 1.14 - 4.18; p = 0.02) were more likely to develop MBM; pts who had liver metastases at the start of PD1i (HR, 1.77; 95% CI, 1.09 - 2.87; p = 0.002) and those who developed MBM during PD1i (HR, 4.81; 95% CI, 3.00 - 7.71; p < 0.0001) had increased risk of death. Conclusions: We found a 26% incidence of MBM after PD1i exposure. Pts that develop MBM are still at higher risk of death despite advances in systemic and local CNS therapy. CNS-only progression was substantially higher in patients with MBM prior to PD1i, supporting a change in the natural history of the disease after PD1i. These findings support the use of CNS imaging to monitor disease during PD1i therapy.