title: A transient increase in eosinophils is associated with prolonged survival in men with metastatic castration-resistant prostate cancer who receive sipuleucel-T.
abstract: Sipuleucel-T is an autologous cellular immunotherapy used to treat asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). Traditional short-term indicators of clinical response commonly used with chemotherapy have not correlated with survival in patients treated with sipuleucel-T. This retrospective study aimed to evaluate laboratory parameters as possible early biomarkers associated with clinical benefit following sipuleucel-T treatment. Patients treated with sipuleucel-T from three randomized, controlled, phase III clinical trials in mCRPC were considered: IMPACT (NCT00065442; n = 512), D9901 (NCT00005947; n = 127), and D9902A (NCT01133704; n = 98). Patients from these trials were included in this study if their samples were analyzed by the central laboratory and if data were available from baseline and ≥ 1 posttreatment time point (n = 377). We found that sipuleucel-T treatment was associated with a transient increase in serum eosinophil count at week 6 that resolved by week 14 in 28% of patients (105 of 377). This eosinophil increase correlated with induced immune response, longer prostate cancer-specific survival [HR, 0.713; 95% confidence interval (CI), 0.525-0.970; P = 0.031], and a trend in overall survival (HR, 0.753; 95% CI, 0.563-1.008; P = 0.057). Median serum globulin protein levels also increased transiently, which was associated with antigen-specific antibody responses; however, this finding did not correlate with longer survival. We conclude that transient increases in eosinophils at week 6 may be a useful, objective, short-term indicator of global immune activation and survival benefit with sipuleucel-T in patients with mCRPC. This observation warrants prospective evaluation in future clinical trials.
authors.affiliation: Department of Medicine, University of Wisconsin Carbone Cancer Center, Madison, Wisconsin. dm3@medicine.wisc.edu.
authors.forename: Douglas G
authors.initials: DG
authors.lastname: McNeel
authors.affiliation: Department of Urology, Indiana University Simon Cancer Center, Indianapolis, Indiana.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Gardner
authors.affiliation: Department of Medicine, University of Washington and Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Celestia S
authors.initials: CS
authors.lastname: Higano
authors.affiliation: Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: Philip W
authors.initials: PW
authors.lastname: Kantoff
authors.affiliation: Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco Comprehensive Cancer Center, San Francisco, California.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Small
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, Washington.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Wener
authors.affiliation: Dendreon Corporation, Seattle, Washington.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Sims
authors.affiliation: Dendreon Corporation, Seattle, Washington.
authors.forename: Todd
authors.initials: T
authors.lastname: DeVries
authors.affiliation: Dendreon Corporation, Seattle, Washington.
authors.forename: Nadeem A
authors.initials: NA
authors.lastname: Sheikh
authors.affiliation: Department of Solid Tumor Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Robert
authors.initials: R
authors.lastname: Dreicer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001798:Blood Proteins / Q000378:metabolism; D001859:Bone Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D004311:Double-Blind Method; D004804:Eosinophils / Q000276:immunology*; D006801:Humans; D053208:Kaplan-Meier Estimate; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood / Q000276:immunology / Q000628:therapy*; D012189:Retrospective Studies; D014020:Tissue Extracts / Q000276:immunology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D001798:Blood Proteins; D019496:Cancer Vaccines; D014020:Tissue Extracts; C511774:sipuleucel-T