A Pilot Study of Hepatic Irradiation with Yttrium-90 Microspheres Followed by Immunotherapy with Ipilimumab and Nivolumab for Metastatic Uveal Melanoma.

Background: Liver metastases from uveal melanoma carry a very poor prognosis. Hepatic artery infusions with Yttrium-90 (⁹⁰Y) resin microspheres have some activity in this disease, and radiation and immunotherapy may be synergistic. The primary objective of this study was to determine the safety and tolerability of sequential ⁹⁰Y resin microspheres and immunotherapy with ipilimumab and nivolumab in metastatic uveal melanoma. Materials and Methods: Twenty-six patients with uveal melanoma with hepatic metastases were entered into a pilot study. Treatment consisted of two infusions of ⁹⁰Y resin microspheres, one to each lobe of the liver, followed in 2-4 weeks by immunotherapy with ipilimumab and nivolumab every 3 weeks for four doses, then maintenance immunotherapy with nivolumab alone. Results: Initial dosing of both ⁹⁰Y and immunotherapy resulted in excessive toxicity. With decreasing the dosage of ⁹⁰Y to limit the normal liver dose to 35Gy and lowering the ipilimumab dose to 1 mg/kg, the toxicity was tolerable, with no apparent change in efficacy. There was one complete and four confirmed partial responses, for an objective response rate of 20% and a disease control rate of 68%. The median progression-free survival was 5.5 months (95% confidence interval [CI]: 1.3-9.7 months), with a median overall survival of 15 months (95% CI: 9.7-20.1 months). Conclusions: With dose reductions, sequential therapy with ⁹⁰Y and immunotherapy with ipilimumab and nivolumab is safe and tolerable, and has activity in metastatic uveal melanoma. These results justify a controlled trial to demonstrate whether ⁹⁰Y resin microspheres add to the utility of combination immunotherapy in this disease. Clinical Trial Registration number: NCT02913417.