Systemic Therapy for Mucosal, Acral, and Uveal Melanoma

Melanoma is a disease that is remarkably heterogeneous. Even cutaneous melanoma, the most common melanoma subtype, is characterized by important biological and clinical differences between disease arising from nonchronically sun-exposed and chronically sun-exposed skin. Acral melanoma, melanomas which arise from skin on the palms of the hands, soles of the feet, or beneath the nails of the fingers or toes, and extracutaneous melanomas, such as those arising from the mucosal surfaces of the body and from the uveal tract of the eye, are uncommon melanoma subtypes also characterized by biological and clinical characteristics distinct from non-acral cutaneous melanoma and distinct from one another. These melanoma subtypes share a more aggressive natural history as well as a lack of association with ultraviolet radiation when compared with non-acral cutaneous disease. Because of the rarity of acral and extracutaneous melanomas, robust clinical trial data are relatively limited when compared with that available for cutaneous melanoma, and management recommendations are frequently based upon consensus opinion and are often extrapolated from the experience in cutaneous melanoma. Importantly, the molecular and immunological differences between non-acral cutaneous melanoma, acral melanoma, mucosal melanoma, and uveal melanoma have critical implications for the appropriate use of systemic therapy in both the advanced disease and adjuvant settings. In this chapter, we review the clinical, molecular, and immunological characteristics of acral, mucosal, and uveal melanoma in the context of systemic therapy, including molecularly targeted and immunological therapies. We discuss the use of systemic therapy in both the advanced disease setting as well as the adjuvant setting. Finally, we review emerging data on new therapeutic options and the use of systemic therapy in additional clinical settings such as in the neoadjuvant setting.