856P Characterization of patients with brain metastases from metastatic uveal melanoma

Abstract

Brain metastases (BM) occur rarely in patients with metastatic uveal melanoma (MUM). However, new therapies have improved survival of patients with MUM and development of extra-hepatic metastases is increasingly common. We aimed to describe the characteristics of patients with MUM who developed BM. In this single-center retrospective study, we identified patients with MUM who presented BM at any time during their clinical course. We collected data regarding age at BM diagnosis, time to development of BM, next generation sequencing (NGS) and multiplex ligation-dependent probe amplification (MLPA) analyses, lines of therapy prior to BM diagnosis, and management of BM. Intracranial progression-free survival (IC-PFS) and overall survival (OS) from BM diagnosis were calculated by the Log-Rank method. From 2014 to 2021, 210 patients with MUM were identified; 22 (10.4%) developed BM. Median age at BM diagnosis was 59 years (49-80); 12 (55%) were male. Median number of systemic treatments prior to BM diagnosis was 2 (0-4) and included anti-PD1 + anti-CTLA4 in 4, anti-PD1 monotherapy in 8, and tebentafusp in 5 patients. Eleven (50%) patients had NGS data available and, following GNAQ/11 mutations (11 patients), BAP1 alterations were the most frequent (4 patients: p.Val171Cysfs*12, p.Thr93_Ala95del, p.S58fs*4, and p.Glu653* each). Three patients had MLPA analysis, and all had chromosome 3 monosomy and 8q gain. Median time from diagnosis of MUM to BM was 16.6 months (0-147). Fifteen (68%) patients had an incidental diagnosis, and 17 (77%) had < 3 BM. Mean size of the largest lesion was 15.9 mm (SD 2.4). Twelve (55%) patients were treated with SRS, and 6 (27.5%) had WBRT. Fourteen (63%) patients received systemic therapy following BM diagnosis, which included anti-PD1 + anti-CTLA4 in 2, anti-PD1 monotherapy in 4, and tebentafusp in 1. From BM diagnosis, median IC-PFS was 4.2 months (95% CI 3.7-4.8), and median OS was 7.4 months (95% CI 3.1-11.7). BM in patients with MUM tend to occur late in the course of disease. Molecular high-risk features are frequent in this population. Surveillance with neuroimaging in patients with long-term control of disease may be warranted.