Introduction: The Unmet Need in Acral Melanoma
For years, the management of advanced melanoma has been revolutionized by the advent of immune checkpoint inhibitors, specifically those targeting the programmed cell death 1 (PD-1) pathway. However, much of the foundational evidence for these therapies was derived from populations with cutaneous melanoma, which is characterized by high ultraviolet (UV) radiation-induced mutational burdens. In contrast, acral melanoma—a subtype occurring on non-sun-exposed surfaces such as the palms, soles, and nail beds—represents a distinct biological and clinical entity.
Acral melanoma is the most common subtype in Asian, African, and Latin American populations, yet it often exhibits a lower tumor mutational burden (TMB) and a more immunosuppressive microenvironment compared to cutaneous melanoma. Consequently, the efficacy of standard PD-1 inhibitors in the acral subtype has historically been less robust, leaving clinicians with a significant therapeutic gap. The MELATORCH trial was designed to address this deficit, evaluating the efficacy and safety of toripalimab, a high-affinity humanized IgG4 monoclonal antibody against PD-1, against the traditional chemotherapy standard, dacarbazine.
