The Impact of Molecular Characteristics on the Efficacy of Frontline Immune Checkpoint Inhibitor Therapy in Patients with Metastatic Melanoma

Abstract

Simple Summary Melanoma is a serious skin cancer, and in East Asian patients it frequently arises at acral sites or on internal mucosal surfaces rather than on sun-exposed skin. These forms tend to respond less well to immunotherapy, the current standard first-line treatment, yet it remains unclear which tumors benefit least. We studied 135 East Asian patients with metastatic melanoma treated with first-line immunotherapy and analyzed the genetic features of their tumors. Tumors carrying BRAF gene fusions and KIT alterations were associated with markedly poorer outcomes. Identifying these subgroups may help clinicians recognize patients unlikely to benefit from immunotherapy alone and guide the development of more effective treatment strategies for this understudied population.