CTLA-4 blockade with ipilimumab: long-term follow-up of 177 patients with metastatic melanoma.

Purpose: Treatment with ipilimumabcan cause objective tumor responses in patients with metastatic melanoma. We have treated 177 evaluable patients in three clinical trials and have long-term follow-up to evaluate the durability of responses. Experimental Design: Patients with metastatic melanoma were treated in three trials from 2002 to 2005. In protocol 1, 56 patients received ipilimumabwith gp100 peptides. In protocol 2, 36 patients received ipilimumabwith interleukin-2. In protocol 3, 85 patients received ipilimumabwith intrapatient dose-escalation and were randomized to receive gp100 peptides. We have analyzed their long-term follow-up and survival data. Results: With median follow-up for protocols 1, 2, and 3 being 92, 84, and 71 months, median survival was 14, 16, and 13 months with 5-year survival rates being 13%, 25%, and 23%, respectively. Patients in protocol 2 had a 17% complete response (CR) rate, compared with 7% in protocol 1 and 6% in protocol 3. These CR rates are higher than previously reported for the same trials because some patients who eventually became complete responders had continual tumor regression months to years after therapy. All but one of the 15 complete responders are ongoing at 54+ to 99+ months. Conclusions: This report provides the longest follow-up of patients with melanoma treated with ipilimumaband shows that ipilimumabcan induce durable, potentially curative tumor regression in a small percentage of patients with metastatic melanoma. The combination of ipilimumaband interleukin-2seems to have an increased CR rate, but this needs to be tested in a randomized trial. Clin Cancer Res; 18(7); 2039–47. ©2012 AACR .