Serum levels of soluble CD163 and CXCL5 may be predictive markers for immune-related adverse events in patients with advanced melanoma treated with nivolumab: a pilot study

Abstract

Antibodies against PD-1, such as nivolumab and pembrolizumab, are widely used in the treatment of various cancers including advanced melanoma. The anti-PD-1 Ab significantly prolongs survival in patients with metastatic melanoma, and its administration in combination with local or systemic therapy may also lead to improved outcomes. Although anti-PD-1 Ab-based combined therapy might be effective for the treatment of advanced melanoma, the associated risk of irAEs is an important consideration. Therefore, being able to predict irAEs is of great interest to oncologists. The purpose of this study was to evaluate the value of using serum levels of sCD163 and CXCL5 to predict irAEs in patients with advanced melanoma who were administered nivolumab. To this end, we analyzed these serum levels in 46 cases of advanced melanoma treated with nivolumab. In addition, the tumor stroma was evaluated by immunohistochemistry and immunofluorescence. We measured the serum levels of sCD163 and CXCL5 on day 0 (immediately before nivolumab administration) and day 42. The serum absolute levels of sCD163 were significantly increased in patients who developed AEs (p = 0.0018). Although there was no significant difference in serum levels of CXCL5, the absolute value of CXCL5 could at least be a supportive marker for the increased absolute levels of serum sCD163. This study suggests that sCD163 and CXCL5 may serve as possible prognostic biomarkers for irAEs in patients with advanced melanoma treated with nivolumab.

Severe pyrexia from nivolumab‐resistant advanced melanoma after successful combined therapy with encorafenib plus binimetinib

“…To investigate the soluble factors that may correlate with the onset of fever spike, we measured sCD163, CXCL9, CXCL10 and CXCL11 before and after the administration of E + B combined therapy at the time of onset of a fever spike. These soluble factors were reported to correlate with the AE of anti‐PD‐1 antibody 6,10 and with the spike of fever in patients with AOSD 5 . Serum sCD163, CXCL9, CXCL10 and CXCL11 were increased in all three cases in parallel with their fever spike, but not in another three patients who had been treated with immune checkpoint inhibitors previously but did not develop pyrexia by E + B combined therapy (Fig.…”

Two cases of dabrafenib and trametinib therapy‐failed advanced melanoma successfully controlled by nivolumab monotherapy

“…In aggregate, TAM were reported as an optimal target for immunotherapy, 6 and TAMrelated products could even be biomarkers for the efficacy and immune related adverse events in cancer patients. [9][10][11] In this report, we describe two cases in which DT therapy for advanced melanoma failed but were successfully controlled by nivolumab monotherapy. The antitumor effects of nivolumab after DT therapy may be augmented by M1-polarized TAM induced by nivolumab.…”

“…reported that reprogramming TAM into inflammatory phenotypes by targeting CD40 and CD115 suppresses melanoma growth in vivo . In aggregate, TAM were reported as an optimal target for immunotherapy, and TAM‐related products could even be biomarkers for the efficacy and immune related adverse events in cancer patients …”

Immune checkpoint inhibitors and irAEs

“…In addition, the need for predictive markers of treatment efficacy and the development of improved treatment avenues therefore remain as acute as ever [3] . sCD163 and CXCL5 may serve as possible prognostic biomarkers for irAEs in patients with advanced melanoma treated with nivolumab [5] .…”