title: Effect of granulocyte/macrophage colony-stimulating factor on vaccination with an allogeneic whole-cell melanoma vaccine.
abstract: OBJECTIVE
  The availability of a variety of immune response modifiers creates an opportunity for improved efficacy of immunotherapy, but it also leads to uncertainty in how to combine agents and how to assess those combinations. We sought to assess the effect of the addition of granulocyte/macrophage colony-stimulating factor (GM-CSF) to vaccination with a melanoma vaccine.
  
  
  METHODS
  Ninety-seven patients with resected melanoma (stage II-IV) were enrolled, stratified by stage, and randomized to receive a cellular melanoma vaccine with or without GM-CSF. The primary endpoint was delayed-type hypersensitivity (DTH) response to melanoma cells. Antibody responses, peripheral leukocyte counts, and survival were also examined.
  
  
  RESULTS
  The GM-CSF arm showed enhanced antibody responses with an increase in IgM titer against the TA90 antigen and increased TA90 immune complexes. This arm also had diminished antimelanoma cell delayed-type hypersensitivity response. Peripheral blood leukocyte profiles showed increases in eosinophils and basophils with decreased monocytes in the GM-CSF arm. These immune changes were accompanied by an increase in early melanoma deaths and a trend toward worse survival with GM-CSF.
  
  
  CONCLUSIONS
  These data suggest that GM-CSF is not helpful as an immune adjuvant in this dose and schedule and raise concern that it may be harmful. Based on the discordant findings of an immune endpoint and clinical outcome, the use of such surrogate endpoints in selecting treatments for further evaluation must be done with a great deal of caution.
authors.affiliation: Sonya Valley Ghidossi Vaccine Laboratory of the Roy E. Coats Research Laboratories of the John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, CA 90404, USA. fariesm@jwci.org
authors.forename: Mark B
authors.initials: MB
authors.lastname: Faries
authors.forename: Eddy C
authors.initials: EC
authors.lastname: Hsueh
authors.forename: Xing
authors.initials: X
authors.lastname: Ye
authors.forename: Mary
authors.initials: M
authors.lastname: Hoban
authors.forename: Donald L
authors.initials: DL
authors.lastname: Morton
mesh_terms: D000276:Adjuvants, Immunologic; D000368:Aged; D019496:Cancer Vaccines / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D007962:Leukocytes / Q000166:cytology; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000628:therapy*; D008875:Middle Aged; D010865:Pilot Projects; D012878:Skin Neoplasms / Q000276:immunology* / Q000628:therapy*
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D016178:Granulocyte-Macrophage Colony-Stimulating Factor