Melanoma Immunotherapy

Melanoma is considered a highly immunogenic tumor due to its high level of somatic mutations and frequent expression of type I interferons. As such, investigators have tested many immunotherapies in patients with metastatic and resected melanoma. Although earlier forms of immunotherapy such as interleukin-2 and interferon alpha had modest efficacy, immune checkpoint inhibitors, including ipilimumab, pembrolizumab, nivolumab, and relatlimab, have demonstrated significant benefit and have transformed the care of melanoma patients. Combinations of immune checkpoint inhibitors (ipilimumab and nivolumab or nivolumab with relatlimab) have become standard first-line therapy for patients with metastatic melanoma, while anti-PD-1 monotherapy (pembrolizumab or nivolumab) is routinely used to treat high-risk resected melanoma. Neoadjuvant immunotherapy is emerging as a promising treatment approach for resectable melanoma at high risk for recurrence. Other forms of immunotherapy include oncolytic viruses such as talimogene laherparepvec, and bispecific T-cell engagers such as tebentafusp have also demonstrated benefit to certain populations of melanoma patients. Finally, newer immunotherapy approaches, including tumor-infiltrating lymphocytes (TILs), vaccines targeting melanoma neoantigens, and antibodies to novel immune checkpoints like T-cell immunoreceptor with immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) are showing promise in recently reported and ongoing clinical trials. In summary, immunotherapies have transformed and now dominate systemic therapy for melanoma patients.