Interleukin-2 was the earliest immunotherapy for metastatic melanoma, approved by the FDA in 1998, followed by interferon-α2b as an adjuvant therapy and ipilimumab (anti-CTLA-4 antibody) as therapy for advanced disease, approved by the U.S. Food and Drug Administration (FDA) for melanoma in March 2011. This evidence concerns the gene CTLA4 and melanoma.