Primary tumor characteristics and next‐generation sequencing mutations as biomarkers for melanoma immunotherapy response

Introduction Considerable advances in melanoma have been realized through immunotherapy. The principal aim was to determine whether primary tumor characteristics or next-generation sequencing (NGS) could serve as markers of immunotherapy response. Methods and results The study cohort consisted of 67 patients who received immunotherapy for recurrent or metastatic melanoma and for whom primary tumor biopsies and pathology reports were available. A subset of 59 patient tumors were profiled using an NGS panel of 50 cancer-related genes. Objective response rate to immunotherapy was assessed using RECIST v1.1 criteria. Progression-free survival (PFS) and overall survival (OS) were used as endpoints. Lymphovascular invasion (LVI) strongly correlated with an increased proportion of immunotherapy responders (p = .002). PFS interval (p = .003) and OS (p = .036) were significantly higher in patients with LVI. NRAS mutation was more strongly correlated with an increased proportion of immunotherapy responders (p =.050). PFS was significantly higher in patients with NRAS mutation (p = .042); no difference in OS (p = .111). Discussion This analysis demonstrates an association between lymphovascular invasion and immunotherapy response. Additionally, NGS mutation analysis demonstrated a potential association between NRAS mutations and immunotherapy response.