Immunotherapy of Metastatic Melanoma

Immunotherapy is part of the new treatments that significantly improved the prognostic of metastatic melanoma patients. The article reviews briefly the old immunotherapeutic approaches e.g., interferon-𝛼2 and interleukin-2, and focuses on immune checkpoint inhibitors such as anti-CTLA-4 inhibitors and anti-PD-1 inhibitors in monotherapy or in combination (dual immune blockade). We detailed the results from CheckMate and KEYNOTTE clinical trials that lead to US Food and Drug Administration and European Medicines Agency approvals of the new agents for the treatment of advanced melanoma. The chapter concentrates on the algorithms for BRAF wild-type and BRAF mutated metastatic melanoma treatments, according to American (NCCN) and European (ESMO) guidelines. We underlined the first line, second line, and subsequent lines of treatment for both melanoma subtypes and for particular cases, such as in-transit metastasis or brain metastasis. A special attention was paid to treatment options for early and late disease progression (primary and acquired resistance after adjuvant therapy). Unfortunately, the new immune agents produce a higher toxicity rate, mainly immune adverse events. Also, these drugs can interact with the gut microbiome and with antibiotics, decreasing the efficacy of immune therapy. Finally, we review the new directions for immune therapy e.g., new immune combinations, the association of immune and targeted therapies, and adoptive cellular therapy with tumor-infiltrating lymphocytes, interleukin-2, and anti-PD-1.