Correlation of increased eosinophil count following sipuleucel-T treatment with outcome in patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC).

Abstract

4650 Background: Sipuleucel-T is the first autologous cellular immunotherapy approved for asymptomatic or minimally symptomatic mCRPC. In the IMPACT trial, pts treated with sipuleucel-T had transient increases in eosinophil counts compared with control. In this retrospective analysis, we assess potential correlations between eosinophilia, overall survival (OS), prostate cancer-specific survival (PCSS) and immune response following sipuleucel-T. Methods: Data from three phase III trials (D9901, D9902A, and IMPACT) were pooled. The analysis included CBCs performed at baseline and wks 2–34. Eosinophilia was defined as either >ULN (with normal baseline), or a max change from baseline within the top quartile, at any time between wks 2–16. Results: Increased eosinophil counts were seen in sipuleucel-T pts by wk 6, decreasing to near baseline by wk 14; eosinophil counts in control pts were stable. Of 377 sipuleucel-T pts eligible for analysis, 105 (27.9%) had eosinophilia. Baseline disease characteristics associated with eosinophilia were indicative of better prognosis (i.e., longer Halabi predicted survival [p=0.007], lower PSA [P=0.033], higher Hgb [p<0.001], and no prior docetaxel [p=0.012]). In univariate analyses, eosinophilia correlated with improved OS (HR=0.75; 95%CI: 0.56–1.01; p=0.057) and PCSS (HR=0.71; 95%CI: 0.53–0.97; p=0.031); trends persisted after adjusting for Halabi. The magnitude of eosinophilia positively correlated with antigen-specific humoral responses (p ≤0.039 for wks 6, 14 and 26) and elevations in the cytokines at wk 6 (IL2 [p=0.011], IL5 [p=0.038] and TARC [p=0.001]). AEs occurring more frequently (p<0.05) in pts with eosinophilia were infusion-related: pyrexia (33.3 v 21.3%) and nausea (19.0 v 10.7%). No cases of hypereosinophilic syndrome were reported. Conclusions: Increases in eosinophils after sipuleucel-T correlated with improved OS and PCSS. Large increases in eosinophil counts were associated with humoral responses and Th2-type cytokine production. Further studies of eosinophilia as a biomarker for sipuleucel-T response, particularly in earlier disease settings, are of interest.