title: Immune modulation of minimal residual disease in early chronic phase chronic myelogenous leukemia: a randomized trial of frontline high-dose imatinib mesylate with or without pegylated interferon alpha-2b and granulocyte-macrophage colony-stimulating factor.
abstract: BACKGROUND
  Most patients with chronic myelogenous leukemia (CML) harbor residual disease, as evidenced by molecular techniques even after treatment with high-dose imatinib (ie, 800 mg/d). Interferon alpha (IFN α) is efficacious in CML likely due to its immunomodulatory properties, and is synergistic in vitro with imatinib and granulocyte macrophage-colony stimulating factor (GM-CSF).
  
  
  METHODS
  A study was undertaken to determine whether adding pegylated (PEG) IFN α-2b and GM-CSF to high-dose imatinib may improve the complete molecular response rate in patients with CML in chronic phase. Ninety-four patients were treated with imatinib 800 mg/d for the first 6 months, then randomly assigned to continue high-dose imatinib alone (n = 49) or in combination with PEG IFN α-2b 0.5 μg/kg/wk and GM-CSF 125 mg/m² 3× weekly (n = 45).
  
  
  RESULTS
  The median follow-up for all patients was 54 months (range, 7-70 months). There were no differences in the rates of complete cytogenetic response (87% vs 90%; P = 1.0), or of major (77% vs 77%; P = 1.0) or complete (11% vs 13%; P = 1.0) molecular response (on the international scale) at 12 months between the 2 arms, or at any time during the study. Adverse events led to PEG IFN α-2b discontinuation in all patients.
  
  
  CONCLUSIONS
  The addition of PEG IFN α-2b and GM-CSF to high-dose imatinib therapy does not improve significantly the cytogenetic or molecular response rates compared with high-dose imatinib alone. The high dropout rate in the PEG IFN α-2b arm may have compromised its potential immunomodulatory benefit.
authors.affiliation: Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. jcortes@mdanderson.org
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Alfonso
authors.initials: A
authors.lastname: Quintás-Cardama
authors.forename: Dan
authors.initials: D
authors.lastname: Jones
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
authors.forename: Charles
authors.initials: C
authors.lastname: Koller
authors.forename: Jody
authors.initials: J
authors.lastname: Hiteshew
authors.forename: Jenny
authors.initials: J
authors.lastname: Shan
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D004334:Drug Administration Schedule; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D000068877:Imatinib Mesylate; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000188:drug therapy*; D010352:Patient Dropouts; D010879:Piperazines / Q000008:administration & dosage*; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011743:Pyrimidines / Q000008:administration & dosage*; D011994:Recombinant Proteins
chemical_list: D001549:Benzamides; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D010879:Piperazines; D011743:Pyrimidines; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000068877:Imatinib Mesylate; C417083:peginterferon alfa-2b