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

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.

Significance of Immunosuppressive Cells as a Target for Immunotherapies in Melanoma and Non-Melanoma Skin Cancers

“…Not only sCD163, but also TAM-related chemokines could provide prognostic markers for the efficacy or development of irAEs by anti-PD1 Ab treatment [81,82]. Baseline serum CXCL5, but not CXCL10 and CCL22, is associated with the efficacy of nivolumab in advanced melanoma [81]. Moreover, increased absolute serum levels of CXCL5 correlated significantly with irAEs by nivolumab [14].…”

Treatment of Advanced Melanoma: Past, Present and Future

“…More recently, TAM-related factors (soluble (s)CD163, CXCL5, (Chemokine (C-C motif) ligand (CCL)19 and CCL26)) could be predictive biomarkers for anti-PD1 Abs monotherapy [64][65][66][67]. In future, these predictive markers might be taken into accounts in combination with conventional markers, such as BRAF mutation, before selecting the protocol for immune therapy.…”

Erfolgreiche Behandlung multipler Melanommetastasen mit einer Kombinationstherapie aus Nivolumab, Ipilimumab und Denosumab

“…In diesem Bericht stellen wir den Fall eines Patienten mit multipel metastasierendem Melanom vor, der mit einer Kombinationstherapie mit Nivolumab, Ipilimumab plus Denosumab behandelt wurde. Obwohl der Patient vor Behandlungsbeginn einen hohen CXCL5-Wert hatte, was für ein Ansprechen auf eine Monotherapie mit anti-PD1-Ak spricht [13], entschieden wir uns aufgrund anderer prognostischer Baseline-Faktoren (Metastasen in 4 Organen) für eine Kombinationstherapie aus Nivolumab plus Ipilimumab und Denosumab. Wie anhand unserer Biomarker-Systeme prognostiziert, lag nach 6 Wochen eine erhöhte Konzentration von löslichem (s)CD163 vor, die auf ein effektives Ansprechen auf die anti-PD1-Ak hindeutete [14].…”