Up to 50% of patients with uveal melanoma develop metastatic uveal melanoma after local treatment
Peak incidence occurs at ~3 years, and as early as 1 year after primary intervention in some patients.3-5
~90% of patients
with metastatic uveal
melanoma have
liver metastasis
Metastases can also occur in the lungs, bone, skin or subcutaneous tissue, and lymph nodes.6
Even with available treatments, metastatic uveal melanoma has a poor prognosis7-10*
~12 mos
~43%
~19%
*historical data
I went from being perfectly healthy…to losing sight in my eye, and then losing my eye itself, to [developing] metastasis four months later. I was already reeling...having a rare cancer...researching the very limited approved treatment options...to then learning that it had already spread quite rapidly.
Patient with uveal melanoma
At first, they thought it was a detached retina, but after an ultrasound with a specialist, I was told I had cancer. I freaked out a little. Nine days later, I had my eye removed. Six months after that, scans showed that it had spread to my liver.
Patient with uveal melanoma
Most patients with metastatic uveal melanoma
have no FDA-approved systemic treatment options12-14
Role of HLA status in select metastatic uveal melanoma treatment approaches15
Not all patients with metastatic uveal melanoma are biologically the same, and one important difference is their HLA type. HLA molecules direct antigen presentation to cytotoxic T cells, shaping immune responsiveness. Because some immunotherapies depend on a specific HLA allele to recognize and target tumor cells, HLA testing helps identify which patients may be candidates for certain treatment.9,16-18
Current FDA-approved treatments address only a subset of patients, highlighting a significant unmet need6,9,12,13
In metastatic uveal melanoma, there is only one FDA-approved systemic therapy, which is limited to patients who are HLA-A*02:01-positive. This leaves the majority of patients who are HLA-A*02:01-negative (~50–70%) with no FDA-approved systemic options.12-14,19
Metastatic distribution informs systemic or local treatment approach
In addition to HLA status, the pattern of metastatic spread is an important consideration in treatment planning. Liver-directed therapies may be considered in patients with hepatic-dominant disease, including those with residual or progressive liver involvement following systemic therapy. However, these approaches do not address extrahepatic disease.9
Other therapies used in metastatic uveal
melanoma are not FDA-approved for this disease and are
associated with additional limitations.20
These NCCN® Category 2A options are based on currently available clinical evidence and may provide clinical benefit for some patients. However, the evidence is primarily derived from small, single-arm studies, the options are not FDA-approved for uveal melanoma, are intravenously administered, and have safety considerations such as immune-mediated adverse reactions.20-23
Combination immune checkpoint inhibitors22,23:
ORR 11.5–18%
Median OS 12.7–19.1 months
Median PFS 3.0–5.5 months
Single-agent immune checkpoint inhibitors21:
ORR 3.4%
Median OS 9.8 months
Median PFS 2.8 months
Chemotherapy (used as later line)7:
—
Median OS 9.2 months
Median PFS 2.6 months
In one survey of 17 patients with metastatic uveal melanoma, they reported facing logistical and emotional burdens from frequent travel to specialized centers and ongoing monitoring. They also reported having to reduce work or rely on family support, adding financial and social burdens.11
Over the last five years I’ve [had to travel] over 230 times. I met people who had to do a second mortgage on their home, [fundraising] accounts, bake sales at their church.
Patient with uveal melanoma
When you have a rare cancer, treatments are not always available locally
Patient with uveal melanoma
Significant unmet needs remain, especially for patients who are
HLA-A*02:01-negative and those who progress on current treatments2,12
[Dr. Smith] provides insights into uveal melanoma, exploring its unique biology, clinical challenges, and current approaches to diagnosis and management.
There is a significant need for targeted therapies that address the unique biology of uveal melanoma.3
FDA, Food and Drug Administration; HLA, human leukocyte antigen; NCCN, National Comprehensive Cancer Network® (NCCN®); ORR, objective response rate; OS, overall survival; PFS, progression-free survival.
1. Ziogas DC, Foteinou D, Theocharopoulos C, et al. State‑of‑the‑art in metastatic uveal melanoma treatment: a 2025 update. Curr Oncol Rep. 2025;27(7):803-821. doi:10.1007/s11912-025-01684-0
2. Hanratty K, Finegan G, Rochfort KD, Kennedy S. Current treatment of uveal melanoma. Cancers (Basel). 2025;17(9):1403. doi:10.3390/cancers17091403
3. Mallone F, Sacchetti M, Lambiase A, Moramarco A. Molecular insights and emerging strategies for treatment of metastatic uveal melanoma. Cancers (Basel). 2020;12(10):2761. doi:10.3390/cancers12102761
4. Shields CL, Samuelson AG, Oh GJ, et al. Conditional metastasis of uveal melanoma in 8091 patients over half-century (51 years) by age group: assessing the entire population and the extremes of age. Invest Ophthalmol Vis Sci. 2023;64(10):7. doi:10.1167/iovs.64.10.7
5. Szalai E, Jiang Y, van Poppelen NM, et al. Association of uveal melanoma metastatic rate with stochastic mutation rate and type of mutation. JAMA Ophthalmol. 2018;136(10):1115-1120. doi:10.1001/jamaophthalmol.2018.2986
6. Diener-West M, Reynolds SM, Agugliaro DJ, et al. Development of metastatic disease after enrollment in the COMS trials for treatment of choroidal melanoma: collaborative Ocular Melanoma Study Group Report No. 26. Arch Ophthalmol. 2005;123(12):1639-1643. doi:10.1001/archopht.123.12.1639
7. Khoja L, Atenafu EG, Suciu S, et al. Meta-analysis in metastatic uveal melanoma to determine progression free and overall survival benchmarks: an international rare cancers initiative (IRCI) ocular melanoma study. Ann Oncol. 2019;30(8):1370-1380. doi:10.1093/annonc/mdz176
8. Rantala ES, Hernberg M, Kivelä TT. Overall survival after treatment for metastatic uveal melanoma: a systematic review and meta-analysis. Melanoma Res. 2019;29(6):561-568. doi:10.1097/CMR.0000000000000575
9. Carvajal RD, Sacco JJ, Jager MJ, et al. Advances in the clinical management of uveal melanoma. Nat Rev Clin Oncol. 2023;20(2):99-115. doi:10.1038/s41571-022-00714-1
10. Key statistics for eye cancer. American Cancer Society. Updated May 5, 2025. Accessed December 22, 2025. https://www.cancer.org/cancer/types/eye-cancer/about/key-statistics.html
11. Ng CA, Luckett T, Mulhern B, Kee D, Lai-Kwon J, Joshua AM. What matters most to people with metastatic uveal melanoma? a qualitative study to inform future measurement of health-related quality of life. Melanoma Res. 2024;34(3):248-257. doi:10.1097/CMR.0000000000000961
12. Koch EAT, Heppt MV, Berking C. The current state of systemic therapy of metastatic uveal melanoma. Am J Clin Dermatol. 2024;25(5):691-700. doi:10.1007/s40257-024-00872-1
13. McKean M, Chmielowski B, Butler MO, et al. ctDNA reduction and clinical efficacy of the darovasertib + crizotinib combination in metastatic uveal melanoma. Poster presented at: European Society for Medical Oncology (ESMO) Congress; October 20-24, 2023; Madrid, Spain.
14. Ciernik A, Ciernik L, Bonczkowitz P, et al. Retrospective multicenter analysis of real-life toxicity and outcome of ipilimumab and nivolumab in metastatic uveal melanoma. Oncologist. 2025;30(7):oyaf173. doi:10.1093/oncolo/oyaf173
15. Olivier T, Haslam A, Tuia J, Prasad V. Eligibility for human leukocyte antigen–based therapeutics by race and ethnicity. JAMA Netw Open. 2023;6(10):e2338612. doi:10.1001/jamanetworkopen.2023.38612
16. Shafer P, Kelly LM, Hoyos V. Cancer Therapy With TCR-Engineered T Cells: current strategies, challenges, and prospects. Front Immunol. 2022;13:835762. doi:10.3389/fimmu.2022.835762
17. Souri Z, Wierenga APA, Mulder A, Jochemsen AG, Jager MJ. HLA expression in uveal melanoma: an indicator of malignancy and a modifiable immunological target. Cancers (Basel). 2019;11(8):1132. doi:10.3390/cancers11081132
18. Yang K, Ahmed Halima A, Chan TA. Antigen presentation in cancer — mechanisms and clinical implications for immunotherapy. Nat Rev Clin Oncol. 2023;20(9):604-623. doi:10.1038/s41571-023-00789-4
19. Saldanha EF, Ribeiro MF, Hirsch I, Spreafico A, Saibil SD, Butler MO. How we treat patients with metastatic uveal melanoma. ESMO Open. 2025;10(4):104496. doi:10.1016/j.esmoop.2025.104496
20. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Melanoma: Uveal V.1.2026. © National Comprehensive Cancer Network, Inc. 2026. All rights reserved. Accessed February 17, 2026. To view the most recent and complete version of the guideline, go online to NCCN.org.
21. Yamada K, Takeuchi M, Fukumoto T, et al. Immune checkpoint inhibitors for metastatic uveal melanoma: a meta-analysis. Sci Rep. 2024;14:7887. doi:10.1038/s41598-024-55675-5
22. Piulats JM, Espinosa E, de la Cruz Merino L, et al. Nivolumab plus ipilimumab for treatment-naive metastatic uveal melanoma: an open-label, multicenter, phase II trial by the Spanish Multidisciplinary Melanoma Group (GEM-1402). J Clin Oncol. 2021;39(6):586-598. doi:10.1200/JCO.20.00550
23. Pelster MS, Gruschkus SK, Bassett R, et al. Nivolumab and ipilimumab in metastatic uveal melanoma: results from a single-arm phase II study. J Clin Oncol. 2021;39(6):599-607. doi:10.1200/JCO.20.00605