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Aim: We previously reported a prospective trial evaluating the safety and efficacy of combining ipilimumab and radiation therapy in patients with metastatic melanoma. Herein, we provide a long-term update on patients with complete response (CR) or partial response (PR). Patients & methods: We continued to follow these patients with serial imaging including computed tomography, PET or MRI. Results: Two of the three patients with CR are still alive and without evidence of melanoma but with chronic treatment-induced hypophysitis. The third patient died of hepatocellular carcinoma, but with no evidence of melanoma. Among the three patients with PR, two achieved CR after pembrolizumab monotherapy. Conclusion: This long-term follow up reveals the striking durability of the CRs, which appears to correlate with a grade 2–3 hypophysitis.