Targeting the IL-2 pathway for the treatment of mucosal melanoma

ABSTRACT Introduction Mucosal melanomas are rare and aggressive forms of cancer that have consistently eluded meaningful recovery with various anticancer therapies. Patients with unresectable mucosal melanomas have benefited from prolonged survival with the use of systemic drugs, including immune checkpoint inhibitors, but prognosis for mucosal malignancies remains inferior compared to cutaneous melanomas. FDA breakthrough and orphan drug designations for novel IL-2 formulations bempegaldesleukin and nemvaleukin highlight the potential for restoring cytokine-based therapy as a viable option in treating mucosal melanomas. Areas covered In this review, we discuss the biological and clinical features of mucosal melanomas, the current therapies available to this patient population including anti-PD1 and targeted therapies, and the potential for integrating novel IL-2 formulations into the existing armamentarium. Recently published clinical trial outcomes evaluating IL-2-based drugs are critically evaluated within the context of the existing treatment landscape for mucosal melanomas. Expert Opinion We conclude that clinical trials are a key priority for eligible patients who may stand to benefit from IL-2 therapy. For patients with unresectable and advanced disease who are unable to participate in trials, anti-PD1 and targeted therapies may still be considered as front- and next-line treatments on a case-by-case basis.