Concurrent treatment with transarterial immunoembolization of hepatic metastases and systemic immune checkpoint inhibitors to overcome immune evasion in patients with metastatic uveal melanoma.

Abstract

Background: Metastatic uveal melanoma (mUM) is an uncommon melanoma subtype, poorly immunogenic with low objective response rates (ORR) to immune checkpoint inhibitors (ICI). Liver-directed therapies (LDT) are commonly used given the strong predilection for hepatic metastases. Transarterial immunoembolization (TAIE) with granulocyte-macrophage colony stimulating factor (GM-CSF) can potentially synergize with concurrent systemic ICI to overcome immune evasion.

Methods: This single-center, retrospective study includes mUM patients with liver-predominant metastases who received TAIE, with/without concurrent systemic ICI (≤ 3 months before/during TAIE). Endpoints included ORR, progression-free survival (PFS), overall survival (OS), and adverse events (AEs).

Results: Between 2016 and 2023, 18 mUM patients (median age 64 years) received TAIE (median 4 procedures/patient). Fourteen patients (78%) received concurrent ICI. ORR was 17% (3/18), all in patients receiving ICI, with partial responses lasting 4.2, 35 + and 46 months. Disease control rate (stable disease or better) was 56% (10/18). Median time to next systemic therapy or death was 19.5 months (range 1.6- 46). Median PFS and OS from first TAIE treatment were 4.9 months (range 0.7-46) and 35 months (range 1.7- 46). Immune-related AEs (IRAE) during concurrent therapy occurred in seven of 10 patients receiving anti-CTLA-4/PD-1 combination, including hepatitis (n = 5; grade 2 in 1, grade 3 in 4). Four of seven patients resumed anti-PD-1 monotherapy without recurrent IRAE.

Conclusions: Concurrent LDT with GM-CSF TAIE and ICI, including anti-CTLA-4/PD-1 combination, is feasible, safe, and can lead to sustained clinical benefit in a subset of mUM patients. OS with this combination compares favorably to published outcomes for systemic therapy or LDT alone.