Abstract
Background: Uveal melanoma is the most common primary intraocular malignancy among adults. It is, nevertheless, a rare disease, with an incidence of approximately one case per 100,000 individuals per year in Europe. Approximately half of tumors will eventually metastasize, and the liver is the organ usually affected. No standard-of-care treatment exists for metastasized uveal melanoma. Chemotherapies or liver-directed treatments do not usually result in long-term tumor control. Immunotherapies are currently the most promising therapy option available. Methods: We reviewed both relevant recent literature on PubMed concerning the treatment of uveal melanoma with immunotherapies, and currently investigated drugs on ClinicalTrials.gov. Our own experiences with immune checkpoint blockers are included in a case series of 20 patients. Results: Because few clinical trials have been conducted for metastasized uveal melanoma, no definitive treatment strategy exists for this rare disease. The outcomes of most immunotherapies are poor, especially compared with cutaneous melanoma. However, encouraging results have been found for some very recently investigated agents such as the bispecific tebentafusp, for which a remarkably increased one-year overall survival rate, and similarly increased disease control rate, were observed in early phase studies. Conclusions: The treatment of metastatic uveal melanoma remains challenging, and almost all patients still die from the disease. Long-term responses might be achievable by means of new immunological strategies. Patients should therefore be referred to large medical centers where they can take part in controlled clinical studies.
Highlights
Uveal melanoma arises from melanocytes of the iris (3–5%), ciliary body (5–8%), or choroid [1,2]
The authors come to the conclusion that the long-term survival of these patients is comparable with the long-term survival of advanced melanoma patients treated with Ipilimumab [23]
Response rates among metastasized patients are in the range 40–50% for anti-programmed cell death protein 1 (PD-1) single-agent therapy and up to 60% for combined immunotherapy with anti-cytotoxic T-lymphocyte-associated Protein 4 (CTLA-4) and anti-PD-1 [28,29], rendering metastasized cutaneous melanoma a potentially curative disease
Summary
Uveal melanoma arises from melanocytes of the iris (3–5%), ciliary body (5–8%), or choroid (approximately 85%) [1,2]. None of these strategies have provided a survival benefit for hepatic metastasized uveal melanoma patients in prospective, randomized studies [17]. This question is, currently under investigation in a trial comparing isolated hepatic perfusion with best alternative care (NCT01785316). Key criteria for measuring the clinical effect of the treatments were incorporated into Table 1, including elevated lactate dehydrogenase (LDH) at baseline, therapy regimen, best response, (overall response rate (ORR) = complete response (CR) + partial response (PR)), median duration of response, (disease control rate (DCR) = CR + PR + stable disease (SD)), durable DCR (DCR ≥ 6 months), and median progression-free survival (PFS).
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