Four key trials have led to several licensed drugs in Stage III melanoma (COMBI-AD Dabrafenib+Tramatenib relapse vs. placebo, hazard ratio [HR] 0.51; CheckMate238 Nivolumab relapse vs. Ipilumimab HR 0.72; Keynote054 Pembroluzimab relapse vs. placebo, HR 0.61; and SWOG1404 Pembroluzimab relapse vs. IFNα-2b or Ipilumimab, HR 0.77).4–7 This durable response has been transformational in the management of patients with macroscopically enlarged lymph nodes where the availability of an effective means of improving disease-specific survival without increasing morbidity. This evidence concerns the gene IFNA2 and melanoma.