Risk Reductions of Recurrence and Mortality in Melanoma Patients Using IFN-α

Interferon-α (IFN-α) is indicated as a systemic adjuvant therapy after surgical resection of clinically detectable melanoma considered at high risk for recurrence and death. Adjuvant IFN-α therapy targets melanoma micrometastasis that is the source of future mortality from melanoma recurrence. The impact of adjuvant IFN-α in melanoma has been the focus of multiple randomized clinical trials that collectively have demonstrated a significant impact on relapse-free survival with several regimens tested. An impact on overall survival (OS) was seen in two of three studies that evaluated the high dose regimen (HDI) in comparison to observation (E1684 trial) and the ganglioside GMK vaccine (E1694 trial). Ongoing studies are evaluating adjuvant therapy with HDI versus CTLA4 blockade (US Intergroup trial E1609) and PD1 inhibition (S1404). Advances in biomarker discovery may ultimately allow targeting of IFN-α therapy to patients most likely to benefit while saving others the toxicities and cost in the absence of predicted efficacy.