Prolonged survival in objective responders to ipilimumab therapy

Background: Ipilimumab is a fully human, anti-CTLA-4 monoclonal antibody that has been associated with complete and partial responses when administered as monotherapy or in combination with a vaccine or chemotherapy in patients with advanced metastatic melanoma. Responses have tended to be durable, many lasting months, but the effect of treatment on overall survival (OS) has not been previously characterized. This follow-up study was undertaken to determine OS for patients with advanced metastatic melanoma previously enrolled in 3 distinct ipilimumab phase I and II studies designed to assess varying ipilimumab dosing regimens performed between 2000 and 2005. Methods: Survival status for patients alive at completion of the core studies was determined. OS was determined by combining survival data from the core and follow-up studies and estimated using the Kaplan-Meier method. Median OS and 95% CI were determined according to Brookmeyer and Crowley. If survival status was unknown or missing then OS was censored at the date of last contact or last visit of the core studies. Results: As of November 29, 2007, follow-up data were available from 132 patients and 18 patients were alive. The median OS (95% CI) for patients in Medarex studies -02, -08, and -15 were 19.4 (5.9, 22.9), 12.9 (10.4, 18.0), and 10.0 (10.0, 11.9) months, respectively. There was a total of 13 responders in all 3 core studies. Survival data were unavailable for 2 responders. The median OS for responders has not been reached with a 25 th percentile of 21.7 months. In contrast, the median OS for non- responders was 10.9 months (95% CI 8.4, 12.6), with 25 th and 75 th percentile OS of 5.7 and 19.4 months, respectively. Additional data will be presented. Conclusions: Median OS for patients with advanced metastatic melanoma administered ipilimumab in these studies appears to compare favorably to that reported in the literature. Overall survival was better in responders than in non-responders.