Evolution of the therapeutic landscape in metastatic uveal melanoma: A single-institution real-world analysis of treatment efficacy and patient survival.

Abstract

e21529 Background: Fifty percent of patients with uveal melanoma (UM) develop metastatic disease (90% to the liver) which is associated with a median overall survival of only one year. Clinical management relies on extrapolation of data from cutaneous melanoma with immune checkpoint inhibitors (ICI), recently approved bispecific agents such as tebentafusp for HLA A02:01 positive patients, and liver directed Hepzato Kit (whole liver perfusion of high dose melphalan). Methods: Upon IRB approval, database search using ICD codes identified 590 patients (pts) who were diagnosed with ocular melanoma since 2014 at Huntsman Cancer Institute (HCI). We further screened for those pts who developed metastatic melanoma and underwent systemic therapy. Clinical data were collected by chart review. Results: 42 unique pts were identified, some treated by multiple lines of therapy. The majority received ICIs (12 anti-PD1 alone and 30 with combination anti-CTLA4 + anti-PD1); ORR were 17% (2/12) and 17% (5/30), with median OS 12.8 and 12.3 mon, respectively. Tebentafusp was given to 3 pts; all had PD but median OS was 23.2 mon. One of 5 pts treated by anti-VEGF +/- anti-PD1 had PR (20%) with median OS of 4.04 mon. Seven patients received Hepzato Kit whole liver perfusion of melphalan, with 5 receiving bridging immunotherapy prior to Hepzato initiation (3 tebentafusp and 2 ipi/nivo); 4/5 had a PR (80%) and one remaining pt had SD, vs 0/2 pts who received Hepzato alone had a response with only one SD. All pts treated at HCI for Hepzato perfusion tolerated without severe AEs. OS analysis of Hepzato cohort requires longer follow up. Translational studies are ongoing to further understand the clinical benefit. Conclusions: ICI had limited efficacy in UM. Tebentafusp and anti-VEGF showed evidence of activity. Combination of immunotherapy with Hepzato whole liver perfusion shows promise that warrants further investigation. Treatment N Median Age Sex (M/F) Best Response (CR/PR/SD/PD/Other) Median PFS (Mon) Median OS (Mon) Median Duration on Tx (Mon) Anti-PD1 12 64 7/5 1/1/4/6/0 2.98 12.78 7.48 Anti-PD1 + Anti-CTLA4 30 54.5 18/12 1/4/5/20/0 2.41 12.3 1.4 Tebentafusp 3 62 2/1 0/0/0/3/0 2.03 23.17 2.6 Anti-VEGF +/- anti-PD1 5 55 3/2 0/1/0/3/1 2.68 4.04 2.76 Hepzato 2 48.5 1/1 0/0/1/0/1 3.96 3.96 3.91 Hepzato + Tebentafusp 3 69 2/1 0/2/1/0/0 7.6 9.1 6.57 Hepzato + ipi/nivo 2 59.5 1/1 0/2/0/0/0 5.09 11.07 8.76