Improved Survival with Ipilimumab in Patients with Metastatic Melanoma

SUMMARY: T lymphocytes play an important role in cell mediated immunity. CTLA-4 (Cytotoxic T-Lymphocyte Antigen 4) also known as CD 152 is a protein expressed on the surface of T lymphocytes and has an inhibitory role in T cell function. Ipilimumab (YERVOY®) is a CTLA-4 targeted monoclonal antibody which was studied in metastatic malignant melanoma. MDX010-20 is a large double blind placebo controlled trial in which 676 HLA-A*0201–positive patients, with pretreated advanced melanoma, were randomly assigned to one of the three treatment groups- YERVOY® along with a placebo (137 patients), YERVOY® administered along with a peptide vaccine gp 100 (403 patients) or peptide vaccine gp 100 along with a placebo (136 patients). Patients receiving YERVOY® along with a peptide vaccine had a median survival of 10.1 months compared to 6.4 months for those who received the vaccine alone. This survival benefit for YERVOY® plus vaccine compared to vaccine alone was seen at 12 months (46% vs 25% ) and 24 months (24% vs 14%) respectively. Approximately 10-15% of the patients treated with YERVOY® experienced Grade 3 or 4 immune-related adverse events compared to 3% when treated with gp100 alone. This landmark study is a significant advance in the treatment of metastatic malignant melanoma, with an overall survival benefit. N Engl J Med 2010; 363:711-723