Immunotherapy in the Management of Sinonasal Mucosal Melanoma: A Systematic Review

Abstract Objective The aim of this work is to comprehensively review and synthesize the literature related to sinonasal mucosal melanoma (SNMM) treatment with immunotherapy, including potentially targetable genetic mutations, survival outcomes, and adverse events. Data Sources Embase, Cochrane, Scopus, and Web of Science. Review Methods The study protocol was designed according to Preferred Reporting Items for Systematic Reviews and Meta‐analysis statement. Databases were searched from inception through May 23, 2023. Results A total of 42 studies met inclusion criteria. Twenty‐four of the included studies reported genetic mutations for a combined 787 patients with SNMM. 8.1% (95% confidence interval, CI: 7.6‐8.6), 18.9% (95% CI: 18.1‐19.8), and 8.5% (95% CI: 8.1‐9.0) of reported patients were positive for BRAF , NRAS , and KIT mutations, respectively. The presence of brisk tumor‐infiltrating lymphocytes was associated with improved recurrence‐free survival and overall survival (OS). Six studies reported a combined 5‐year OS after adjuvant immunotherapy treatment of 42.6% (95% CI: 39.4‐45.8). Thirteen studies encompassing 117 patients reported adjuvant or salvage immune checkpoint inhibitor (ICI) immunotherapy response rates: 40.2% (95% CI: 36.8‐43.6) had a positive response (tumor volume reduction or resolution). Eleven studies reported direct comparisons between SNMM patients treated with or without immunotherapy; the majority (7/11) reported survival benefit for their entire cohort or select subgroups of SNMM patients. With the transition to modern ICIs, there is a stronger trend toward survival improvement with adjuvant ICI. Tumors with Ki67 <40% may respond better to ICI's. Conclusion ICI therapy can be an effective in select SNMM patients, especially those with advanced/metastatic disease.