Serum Level of Soluble CD163 May Be a Predictive Marker of the Effectiveness of Nivolumab in Patients With Advanced Cutaneous Melanoma.

Taku Fujimura,Yuki Yamamoto,Yumi Nonomura,Naoko Wada,Kayo Tanita,Hiroshi Uchi,Takanori Hidaka,Setsuya Aiba,Ryota Tanaka,Yasuhiro Fujisawa,Atsushi Otsuka,Akira Hashimoto,Takeru Funakoshi,Hiroo Hata,Yota Sato,Koji Yoshino,Hisako Okuhira,Megumi Aoki,Yahiko Kambayashi ,Kimiaki Imafuku ,Satoru Matsushita ,Hiroyuki Irié

doi:10.3389/fonc.2018.00530

Abstract

Antibodies against programmed cell death protein 1, such as nivolumab and pembrolizumab, are widely used for treating various cancers, including advanced melanoma. Nivolumab significantly prolongs survival in patients with metastatic melanoma, and sequential administration with lipilimumab may improve outcomes when switched at the appropriate time. Biomarkers are therefore needed to evaluate nivolumab efficacy soon after first administration. This study analyzed serum levels of soluble cluster of differentiation 163 (sCD163) in 59 cases of advanced cutaneous melanoma and 16 cases of advanced mucosal melanoma treated using nivolumab. Serum levels of sCD163 were significantly increased after 6 weeks in responders compared to non-responders after initial administration of nivolumab for cutaneous melanoma. In contrast, no significant difference between responders and non-responders was seen among patients with non-cutaneous melanoma. These results suggest that sCD163 may be useful as a biomarker for selecting patients with advanced cutaneous melanoma most likely to benefit from anti-melanoma immunotherapy.

Highlights

The programmed cell death protein 1/programmed death-ligand 1 (PD-1/progressive disease (PD)-L1) pathway plays a critical role in tumor immune response
Because nivolumab shows higher efficacy than other antimelanoma drugs [1, 17], and induces a longer duration of anti-tumor response than BRAF/MEK inhibitors [18, 19], oncologists have been interested in combining nivolumab with agents that enhance anti-tumor immune responses in patients with metastatic melanoma [1,2,3, 20]
To avoid severe AEs caused by ipilimumab, predictive biomarkers are needed to evaluate the efficacy of nivolumab monotherapy at 2–3 months after first administration, to prepare for any planned switch from nivolumab to ipilimumab

Summary

Introduction

The programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) pathway plays a critical role in tumor immune response. Previous reports have suggested ipilimumab is useful for treating advanced melanoma, in combination with other anti-melanoma reagents [1,2,3, 5]. The efficacy of ipilimumab in patients with nivolumab-resistant melanoma is extremely low after objective tumor progression [7]. Because both coadministration of nivolumab and ipilimumab and sequential administration of nivolumab and ipilimumab with a planned switch leads to a high frequency of immune-related adverse events (irAEs) in patients with advanced melanoma [1, 3], determining the efficacy of nivolumab monotherapy before the planned switch from nivolumab to ipilimumab is important

Methods

Results

Conclusion