CTLA-4 Blockade with Ipilimumab: Long-Term Follow-up of 177 Patients with Metastatic Melanoma
Cette étude présente les données relatives au suivi à long terme de 177 patients inclus, entre 2002 et 2005, dans trois essais cliniques évaluant l'ipilumumab pour le traitement d'un mélanome métastatique
Purpose: Treatment with ipilimumab can 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. Patients and Methods: Patients with metastatic melanoma were treated in three trials from 2002 to 2005: In Protocol 1, fifty-six patients received ipilimumab with gp100 peptides. In Protocol 2, thirty-six patients received ipilimumab with interleukin-2. In Protocol 3, eighty-five patients received ipilimumab with intra-patient 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 five-year survival being 13%, 25%, and 23%, respectively. Patients in Protocol 2 had a 17% complete response (CR) rate, compared to 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 CRs 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 melanoma patients treated with ipilimumab and shows that ipilimumab can induce durable, potentially curative tumor regression in a small percentage of patients with metastatic melanoma. The combination of ipilimumab and IL-2 appears to have an increased CR rate, but this needs to be tested in a randomized trial.