Mucosal melanoma: epidemiology, biology, management and the role of immunotherapy

ABSTRACT

Introduction: Mucosal melanoma (MM) is a rare, aggressive subtype of melanoma arising from melanocytes in mucosal surfaces. Patients with MM have poorer stage-matched prognosis than those with cutaneous melanoma (CM). Immune checkpoint inhibition has improved outcomes for patients with advanced CM, but data on the efficacy of immunotherapy in MM is limited.

Areas covered: This article reviews the epidemiology and biology of MM, the general approach to management, the role of targeted therapy, and recent advances in immunotherapy for the treatment of MM.

Expert opinion: Immune checkpoint inhibition demonstrates significant clinical activity in MM, though the effects are more modest than those seen in CM. Clinical trial enrollment is encouraged whenever possible. All patients should have their tumors evaluated for BRAF and KIT alterations. If a trial is not available, we recommend front-line treatment with the combination of nivolumab and ipilimumab, even in the presence of an actionable mutation, for patients with advanced disease and adequate performance status. Anti-PD-1 monotherapy or targeted therapy is also a reasonable option in appropriate cases. Ongoing efforts to optimize patient selection, evaluate the role of immunotherapy in the adjuvant setting, and develop combinatorial strategies to improve the efficacy of checkpoint inhibition in MM are needed.

KEYWORDS:

• Mucosal melanoma
• immunotherapy
• checkpoint inhibition
• PD-1

Article highlights

• Mucosal melanoma is a rare subtype (1.3%) of melanoma that is epidemiologically and biologically distinct from cutaneous melanoma.

• Outcomes for patients with advanced mucosal melanoma are poor, with a 5-year overall survival rate of only 25%.

• KIT-targeted therapy has demonstrated efficacy, particularly in mucosal melanomas harboring exon 11 or 13 KIT mutations, with occasional durable responses.

• Data supporting the efficacy of immunotherapy in mucosal melanoma is limited and derives from retrospective studies and subgroup analyses; anti-PD-1 therapy has significant clinical activity with a ~25% response rate, and combined immune checkpoint inhibition produces an even higher response rate of 37%.

• All patients with advanced mucosal melanoma should be considered for enrollment in a clinical trial and should have their tumors evaluated for BRAF and KIT alterations. If a clinical trial is not an option, we recommend front-line treatment with the combination of nivolumab and ipilimumab for patients with adequate performance status.

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Declaration of interest

R Carvajal is a consultant for AstraZeneca, Bristol Meyers-Squibb, Iconic Therapeutics, Janssen, Merck, Novartis, Roche/Genentech and Thomson Reuters. They are also on the advisory board for Aura Biosciences, Chimeron and Regenix. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.