The relationship between tumor-infiltrating lymphocytes, PD-L1 expression, and clinical outcomes of Asian melanoma patients treated with anti-PD-1 antibody.

Abstract

e22010 Background: Clinical feature of Asian melanoma patients are distinct from those of Western patients. Acral and mucosal melanomas, which are common in Asian populations, predominantly occur in sun-protected areas. Immune-checkpoint inhibitors are standard treatment for inoperable melanoma, however, they are less effective against acral and mucosal melanomas. The aim of our study is to investigate the expression, clinical significance and association of programmed death-ligand 1 (PD-L1) with tumor-infiltrating lymphocytes (TIL) in Asian melanoma patient treated with anti-PD-1 therapy. Methods: Patients with unresectable stage III or metastatic stage IV melanoma who began anti-PD-1 antibody therapy between February 2016 and September 2018 were enrolled. Immunohistochemistry was used to evaluate PD-L1 expression and stromal CD8+ TIL, and PD-1+ TIL densities within the intratumoral regions and associated stromal regions. Baseline characteristics and blood parameters including neutrophil to lymphocyte ratio (NLR) were assessed, and outcome and adverse events were evaluated according to subtypes. Results: Of the 57 cases, the most common type was acral melanoma (n = 28, 49.1%) followed by mucosal melanoma (n = 19, 33.3%) and cutaneous (n = 10, 17.5%). The overall response was 8.8 % and disease control rate was 33.3%. The median progression-free survival (PFS) was 18.0 months (95% confidence interval, 12.57 to 23.43), and there was no difference in PFS according to subtypes. Overall, 29.8% (n = 17) showed PD-L1 expression in tumor cells and 26.3% in immune cells. PD-L1, CD8+TIL, LDH and BRAFV600 statues were not associated with response or survival. NLR (≥ 5) were independent poor prognostic factors by multivariate analysis. Conclusions: In our study, anti-PD-1 therapy showed less effective compared to western patients. High NLR (≥ 5) could predict response of anti-PD-1 therapy in patients with Asian melanoma. Considering the differences in genetic backgrounds and therapeutic efficacy of immunotherapy, specialized therapeutic strategies for Asian melanoma should be established.