Association of Baseline Serum Levels of CXCL5 With the Efficacy of Nivolumab in Advanced Melanoma.

Taku Fujimura,Hiroshi Uchi,Setsuya Aiba,Naoko Wada,Yuki Yamamoto,Yasuhiro Fujisawa,Hisako Okuhira,Takeru Funakoshi,Akira Hashimoto,Chunbing Lyu,Yota Sato,Ryota Tanaka,Atsushi Otsuka,Hiroo Hata,Ryo Amagai,Koji Yoshino,Kayo Tanita,Yumi Nonomura,Yahiko Kambayashi ,Satoru Matsushita

doi:10.3389/fmed.2019.00086

Abstract

Anti-programmed cell death protein 1 (PD1) antibodies are in wide use for the treatment of various cancers. PD1 antibody-based immunotherapy, co-administration of nivolumab and ipilimumab, is one of the optimal immunotherapies, especially in advanced melanoma with high tumor mutation burden. Since this combined therapy leads to a high frequency of serious immune-related adverse events (irAEs) in patients with advanced melanoma, biomarkers are needed to evaluate nivolumab efficacy to avoid serious irAEs caused by ipilimumab. This study analyzed baseline serum levels of CXCL5, CXCL10, and CCL22 in 46 cases of advanced cutaneous melanoma treated with nivolumab. Baseline serum levels of CXCL5 were significantly higher in responders than in non-responders. In contrast, there were no significant differences in baseline serum levels of CXCL10 and CCL22 between responders and non-responders. These results suggest that baseline serum levels of CXCL5 may be useful as a biomarker for identifying patients with advanced cutaneous melanoma most likely to benefit from anti-melanoma immunotherapy.

Highlights

Anti-programmed cell death protein 1 (PD-1) antibodies such as nivolumab and pembrolizumab are in wide use for the treatment of various cancers, including advanced melanoma [1, 2], but cost-effective analyses of their use are sometimes controversial [3]
As previously reported, increased levels of soluble(s) CD163 at 6 weeks could predict the efficacy of nivolumab monotherapy 2–3 months after its first administration for the treatment of advanced cutaneous melanoma [24]
Since serum sCD163 and CXCL5 are, at least in part, derived from CD163+ tumorassociated macrophages (TAMs) that are activated by periostin [24, 26], and chemokine profiles from TAMs are determined by the stimulation of stromal factors [27], spontaneously produced TAM-related factors could be detected in serum from melanoma patients [17, 25, 27]

Summary

Introduction

Anti-programmed cell death protein 1 (PD-1) antibodies such as nivolumab and pembrolizumab are in wide use for the treatment of various cancers, including advanced melanoma [1, 2], but cost-effective analyses of their use are sometimes controversial [3]. The efficacies of nivolumab and pembrolizumab in Japan have been reported to be 34.1% and 24.1%, respectively [7, 8], suggesting that another drug that could enhance the anti-tumor immune response in melanoma is needed. Ipilimumab is a fully humanized immunoglobulin (Ig)G1 monoclonal antibody that blocks cytotoxic T-lymphocyte antigen (CTLA-4) and is one of the promising drugs that enhance the anti-tumor immune response for patients with advanced melanoma with or without BRAF gene mutation in combination with nivolumab [1, 4, 9]. In addition to co-administration of nivolumab and ipilimumab, sequential administration of nivolumab and ipilimumab with a planned switch leads to high efficacy in the treatment of advanced melanoma [4, 9]. Determining the efficacy of nivolumab monotherapy before starting first-line immune therapy for melanoma is important

Methods

Results

Conclusion