• Amod A Sarnaik, Bin Yu, Daohai Yu, Dawn Morelli, Maclean Hall, Dilip Bogle, Lulu Yan, Stephan Targan, Jolie Solomon, Geoff Nichol, Michael Yellin, and Jeffrey S Weber.
• Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, Florida 33612, USA.
• Clin Cancer Res. 2011 Feb 15;17(4):896-906.

PurposeTo determine safety and feasibility of adjuvant ipilimumab following resection of high-risk melanoma and to identify surrogate markers for benefit.Experimental DesignIn this phase II trial, 75 patients with resected stage IIIc/IV melanoma received the CTLA-4 antibody ipilimumab every 6 to 8 weeks for 1 year. Eligible patients received further maintenance treatments. The first 25 patients received 3 mg/kg of ipilimumab, and an additional 50 patients received 10 mg/kg. HLA-A*0201+ patients received multipeptide immunizations in combination with ipilimumab. Leukapheresis was performed prior to and 6 months after initiation of treatment.ResultsMedian overall and relapse-free survivals were not reached after a median follow-up of 29.5 months. Significant immune-related adverse events were observed in 28 of 75 patients and were positively associated with longer relapse-free survival. Antigen-specific T cell responses to vaccine were variable, and vaccine combination was not associated with additional benefit. No effects on T regulatory cells were observed. Higher changes in Th-17 inducible frequency were a surrogate marker of freedom from relapse (P = 0.047), and higher baseline C-reactive protein (CRP) levels were associated with freedom from relapse (P = 0.035).ConclusionsAdjuvant ipilimumab following resection of melanoma at high risk for relapse appeared to be associated with improved outcome compared to historical reports. Significant immune-related adverse events were generally reversible and appeared to be associated with improved relapse-free survival. Although vaccination failed to induce a consistent in vitro measurable response, a higher change in Th-17 inducible cells and higher baseline CRP levels were positively associated with freedom from relapse.©2010 AACR.

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