Real-world outcomes of dual checkpoint inhibition (nivolumab + ipilimumab) versus anti-PD-1 monotherapy in metastatic uveal melanoma: Impact of local therapy and adjusted survival analysis—A multicenter retrospective study in Russia.

9548 Background: Metastatic uveal melanoma (mUM) remains a rare and aggressive malignancy. Immune checkpoint inhibitors (ICI) demonstrate modest activity, and real-world evidence comparing dual (nivolumab + ipilimumab) versus anti-PD-1 monotherapy, as well as the additive role of local therapy is limited. Methods: Multicenter retrospective observational study conducted in Russia (IRB-approved at participating centers). Outcomes assessed: median progression-free survival (mPFS), median overall survival (mOS), objective response rate (ORR), disease control rate (DCR), and grade ≥3 immune-related adverse events (irAEs). Stratified by treatment line, ICI type, and local therapy use. Univariable Cox proportional hazards regression was performed. Results: Patients with metastatic uveal melanoma treated between 2019 and 2025 were included (n=262). Of these, 25 patients (9.5%) who did not receive systemic treatment or received only palliative care were excluded. Among the full cohort: 158 (60.3%) were female, median age at primary diagnosis was 55.9 years, median time to metastatic disease was 2.42 years. Liver metastases were present in 90.8%. After exclusion, 237 patients were analyzed for survival. Results are presented in Table 1. Univariable Cox regression (after exclusion n=237): Dual ICI exposure (yes vs no): HR 0.60 (95% CI 0.44–0.84, p=0.003); Any ICI exposure (yes vs no): HR ≈0.72 (p=0.102) — non-significant trend. Conclusions: Dual ICI (nivolumab + ipilimumab) was associated with improved overall survival (HR 0.60, p=0.003), particularly with combination with local therapy (predominantly IHP, STRT, and TACE), which substantially enhanced ORR, DCR, PFS, and OS across ICI types. Patients who were unable to receive ICI in the first-line setting may be candidates for this option in the second-line; however, this requires further investigation through subgroup comparative analyses. Results. Treatment Line ICI Type Local Therapy n mPFS, mo (95% CI) mOS, mo (95% CI) ORR (%) DCR (%) Gr ≥3 irAEs (%) First-line Dual (nivo+ipi) Without 28 3.5 (3.0–6.6) 18.4 (13.4–33.5) 10.7 28.6 39.3 First-line Dual (nivo+ipi) IHP 60% STRT 35%TACE 5% 20 7.5 (6.2–18.2) 45.7 (23.4–NR) 45.0 80.0 45.0 First-line Mono anti-PD-1 Without 47 3.1 (2.8–3.7) 18.8 (11.9–27.5) 2.1 14.9 2.1 First-line Mono anti-PD-1 STRT 50%IHP 40%TACE 6.7%RFA 3.3% 30 7.53 (4.5–12.3) 27.9 (18.6–NR) 36.7 60.0 16.7 Second-line Dual Without 35 3.3 (2.5–5.5) 13.1 (9.3–18.8) 2.9 31.4 45.7 Second-line Dual STRT 100% 3 9.3 (8.7–NR) 39.1 (9.6–NR) 33.3 100.0 33.3 Second-line Mono anti-PD-1 Without 15 9.0 (5.2–21.6) 21.3 (14.8–NR) 13.3 46.7 0 Second-line Mono anti-PD-1 STRT 50%IHP 25%TACE 25% 8