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

ABSTRACT

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.