Clinical characteristics of patients with metastatic uveal melanoma and assessment of long-term survivors.

Abstract

e21509 Background: Metastatic uveal melanoma (MUM) is a rare malignancy with poor prognosis and limited systemic treatment options. This study evaluates prognostic factors and treatment outcomes in patients with MUM managed at a tertiary reference center. Methods: 91 patients with MUM treated between 2012 and 2025 were evaluated. Demographic, and clinical data were collected. Survival was analyzed using Kaplan–Meier and Cox regression models. Results: Among 91 patients, 46 (50.5%) were male, with a median age of 61 years. Most of the patients had metachronous metastases (91%) and median disease-free interval (DFI) was 32 months. Liver metastases were identified in 95%. Immunotherapy (IO) was used in 67 (74%) patients, including 14 patients in the first-line setting. IO achieved an ORR of 7% and a disease control rate of 64%. Tebentafusp was not available in our country. Locoregional therapies (LT) were administered in 56%. Median overall survival (OS) for the entire cohort was 16.6 months (95% CI, 13.1–20.1). On multivariate Cox regression analysis, female sex, longer DFI (>36 months), lower baseline AST levels, and receipt of LT were independently associated with improved OS. Patients who received combined IO (anti-PD1 plus anti-CTLA4; n=21) had a trend towards longer OS compared to those who received single agent IO (anti-PD1 alone or anti-CTLA4 alone; n=46) as initial IO regimen (HR 0.51; 95%CI 0.26-0.99, p=0.049). 30 patients (33%) survived more than 24 months following the diagnosis of metastatic disease. 97% of these patients had metachronous metastases, 67% had DFI >36 months, 60% had liver directed LT, 67% were females and 70% had undergone enucleation as the primary treatment. Conclusions: This real-world study showed modest efficacy of IO in the treatment of MUM. Combination IO demonstrated a trend toward improved OS compared to mono-IO. Liver directed LT appeared to provide the greatest benefit. Long DFI in patients with metachronous metastatic disease, female sex, and normal transaminase levels are other prognostic factors associated with improved OS. Univariate and multivariate Cox regression analysis for overall survival. Variables Univariate HR (95% CI) Univariate p value Multivariate HR (95% CI) Multivariate p value Female (ref: male) 0.47 (0.29–0.77) 0.003 0.43 (0.24–0.79) 0.007 DFI ≤ 36 mo (ref: >36 mo) 2.28 (1.40–3.70) <0.001 2.30 (1.21–4.35) 0.011 Locoregional therapy: Yes (ref: No) 0.35 (0.22–0.58) <0.001 0.32 (0.17–0.57) <0.001 AST >ULN (ref: ≤ULN) 2.85 (1.56–5.21) <0.001 2.78 (1.27–6.09) 0.01 ALP >ULN (ref: ≤ULN) 2.30 (1.27–4.15) 0.006 1.44 (0.57–3.63) 0.43 LDH >ULN (ref: ≤ULN) 2.08 (1.24–3.50) 0.005 1.49 (0.83–2.65) 0.17 Any-line immunotherapy: Yes (ref: No) 0.56 (0.34–0.93) 0.026 1.04 (0.43–2.55) 0.92 ALP: Alkaline phosphatase, AST: Aspartate aminotransferase, DFI: Disease-free interval, HR: Hazard ratio, LDH: Lactate dehydrogenase, ref: Reference, ULN: Upper limit normal.