Abstract
Treatment options for patients with metastatic melanoma have expanded rapidly since the approval of ipilimumab by the U.S. Food and Drug Administration in 2011. Cytokines such as interferon and interleukin-2 were approved in 1995 and 1998 respectively. However, the effect on survival was marginal, and the toxicity, substantial. Multiple vaccine studies likewise failed to show improvements in survival. The “Holy Grail” came with the discovery of immune checkpoints, and the first metastatic melanoma trial to show an improvement in overall survival involved the use of an immune checkpoint inhibitor against ctla-4: ipilimumab. Since then, the field of immuno-oncology has exploded, with approvals for PD-1 inhibitors and discovery, in clinical trials, of several novel checkpoints such as tim-3, lag-3, and others. In fact more than 950 novel immunotherapy drugs are currently being trialled. Recently, combinations of ctla-4 and PD-1 inhibitors have been associated with 1-year survival rates exceeding 80% and 4-year survival rates greater than 50%. In no tumour has as much progress been made in the last 5 years as in melanoma, and the efforts to unravel and exploit mechanisms used by the tumour to avoid immune detection are just beginning.