Since the first approval for
immune checkpoint inhibitors (ICIs) for the treatment of cutaneous
melanoma more than a decade ago,
immunotherapy has completely transformed the treatment landscape of this
chemotherapy-resistant disease. Combination regimens including ICIs directed against
programmed cell death protein 1 (PD-1) with anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) agents or, more recently, anti-lymphocyte-activation gene 3 (LAG-3) agents, have gained regulatory approvals for the treatment of metastatic cutaneous
melanoma, with long-term follow-up data suggesting the possibility of cure for some patients with advanced disease. In the resectable setting, adjuvant ICIs prolong recurrence-free survival, and neoadjuvant strategies are an active area of investigation. Other
immunotherapy strategies, such as
oncolytic virotherapy for
injectable cutaneous
melanoma and bispecific T-cell engager
therapy for
HLA-A*02:01 genotype-positive
uveal melanoma, are also available to patients. Despite the remarkable efficacy of these regimens for many patients with cutaneous
melanoma, traditional
immunotherapy biomarkers (ie,
programmed death-ligand 1 expression,
tumor mutational burden, T-cell infiltrate and/or microsatellite stability) have failed to reliably predict response. Furthermore, ICIs are associated with unique toxicity profiles, particularly for the highly active combination of anti-PD-1 plus anti-CTLA-4 agents. The Society for
Immunotherapy of
Cancer (SITC) convened a panel of experts to develop this clinical practice guideline on
immunotherapy for the treatment of
melanoma, including rare subtypes of the disease (eg, uveal, mucosal), with the goal of improving patient care by providing guidance to the oncology community. Drawing from published data and clinical experience, the Expert Panel developed evidence- and consensus-based recommendations for healthcare professionals using
immunotherapy to treat
melanoma, with topics including
therapy selection in the advanced and perioperative settings, intratumoral
immunotherapy, when to use
immunotherapy for patients with BRAFV600-mutated disease, management of patients with
brain metastases, evaluation of treatment response, special patient populations, patient education, quality of life, and survivorship, among others.