Ipilimumab for metastatic melanoma

Abstract

Malignant melanoma is currently the fifth most common cancer in American men and the seventh most common in American women. Despite the advances made for early disease, the prognosis for metastatic melanoma is dismal, with an overall 5-year mortality rate of 90%. It is estimated that 8,000 Americans will die of melanoma in 2012. Recent advances in the understanding of the complex cellular interactions regulating cancer immunity have led to new strategies in the development of cancer immunotherapy. The discovery of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), a negative regulator of immune activity, has led to the development of a monoclonal antibody, ipilimumab, that can abrogate immune suppression. Ipilimumab is the first immunotherapy approved by the FDA for patients with advanced melanoma based on the overall survival benefit in a phase III setting. It represents a paradigm shift in melanoma management with its success promoting the evaluation of monoclonal antibodies targeted against a number of other regulatory checkpoints in patients with advanced melanoma.