Abstract
Uveal melanoma is a common intraocular malignant tumor that is uniformly fatal once metastatic. No effective adjuvant therapy currently exists to reduce the risk of distant metastasis after definitive treatment of the primary lesion. Immunotherapy has been used effectively in the adjuvant setting in locally advanced cutaneous melanoma. We performed a Phase I/II clinical trial of adjuvant ipilimumab in high-risk primary uveal melanoma with distant metastasis-free survival (DMFS) as the primary objective. A total of 10 patients with genomically high-risk disease were treated: three at a dose of 3 mg/kg and seven at 10 mg/kg. Two of the seven patients at the higher dose had to discontinue therapy secondary to grade 3 toxicity. At 36 months follow-up, 80% of patients had no evidence of distant disease (95% CI, 58.7–100). With recent advancements in CTLA-4 inhibition, PD-1 inhibition, and combined checkpoint blockade, immunotherapy is a promising avenue of treatment in uveal melanoma. Further clinical trials are needed to elucidate the role of immunotherapy in the adjuvant setting.
Highlights
Uveal melanoma is the most common primary intraocular malignant tumor in adults and represents approximately 5% of all melanoma diagnoses [1,2]
Risk-stratified as DecisionDx-UM® Class 2, which carries a historical distant metastasis-free survival (DMFS) of 50% at 32–36 months
Prospective studies in uveal melanoma tend to have lower accrual, given the rarity of disease, and use of historical control is not uncommon. While this data is promising, it is not possible to infer from our analysis that adjuvant ipilimumab conferred a statistically significant DMFS
Summary
Uveal melanoma is the most common primary intraocular malignant tumor in adults and represents approximately 5% of all melanoma diagnoses [1,2]. Primary uveal melanoma is definitively treated with brachytherapy, proton beam radiation, or enucleation [3,4], and clinical evidence of metastatic disease at presentation is rare [5]. Approximately 50% of patients with uveal melanoma will relapse with a uniformly fatal metastatic disease and have a median overall survival period of less than 12 months [6,7,8,9]. Features of the primary tumor prognostic for an increased risk of distant metastatic disease include tumor size, AJCC staging, and genomic analysis demonstrating monosomy 3 or DecisionDx-UM high-risk molecular gene signature [10,11,12,13,14]. There is no consensus regarding adjuvant therapy for reducing the risk of distant metastases. Low-dose interferon, hepatic arterial fotemustine, and sunitinib have either failed to show an overall survival benefit or been limited by study design [15,16,17,18]
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