Correlation of absolute and relative eosinophil counts with immune-related adverse events in melanoma patients treated with ipilimumab.

Abstract

9096 Background: Ipilimumab (ipi) has shown significant improvements in overall survival (OS) for patients (pts) with advanced melanoma in randomized phase III trials. Easily obtainable pre- or on-treatment biomarkers would be helpful to optimize this therapy. In a prior analysis, IL-17 levels correlated with immune-related adverse events (irAEs), and IL-17 and eosinophils are immunologically related. In one prior single institution study of 73 ipi-treated pts, an increase in absolute eosinophil count (AEC) was associated with improved OS. Whether this finding correlates with other clinical outcomes such as immune-related adverse events (irAEs) or is reproducible in larger, multicenter analyses remains unknown. Methods: 156 pts with advanced melanoma treated with ipi at the approved standard dose of 3mg/kg in 4 institutions (Medical University of Vienna, University of Zurich, University of Lausanne, and Memorial Sloan-Kettering Cancer Center) between 2010 and 2013 were retrospectively analyzed. Baseline (B/L), week (W) 4 and W7 absolute and relative eosinophil (AEC and REC) counts and occurrence of irAEs were noted. Wilcoxon rank-sum test was performed for analyzing the association of AEC and REC with irAEs. OS was calculated from date of first ipi dose to date of death or last followup. The association between B/L, W4 and W7 levels of AEC and REC and OS was assessed using Cox proportional hazards regression. Results: The change in AEC from B/L to W4 and from B/L to W7 was significantly associated with the occurrence of any irAE (p=0.032 and p=0.007, respectively). As continuous variables at W4, AEC and REC were significantly associated with irAEs (p=0.018 and p=0.275, respectively). At W7 AEC was significantly associated with irAEs (p=0.019) but REC was not (p=0.074). Neither AEC nor REC at B/L was significantly associated with irAEs. Neither the change in AEC nor REC from B/L to W4 was associated with OS. Conclusions: Eosinophils were associated with irAEs but not OS during ipi treatment. Given functional links between IL-17 and eosinophils, and the correlation of both IL-17 and eosinophils with irAEs, further study of the mechanistic role of this pathway in pts with irAEs is warranted.