title: Imatinib plus peginterferon alfa-2a in chronic myeloid leukemia.
abstract: BACKGROUND
  Imatinib (400 mg daily) is considered the best initial therapy for patients with newly diagnosed chronic myeloid leukemia (CML) in the chronic phase. However, only a minority of patients treated with imatinib have a complete molecular remission.
  
  
  METHODS
  We randomly assigned 636 patients with untreated chronic-phase CML to receive imatinib alone at a dose of 400 mg daily, imatinib (400 mg daily) plus cytarabine (20 mg per square meter of body-surface area per day on days 15 through 28 of each 28-day cycle) or pegylated interferon (peginterferon) alfa-2a (90 μg weekly), or imatinib alone at a dose of 600 mg daily. Molecular and cytogenetic responses, time to treatment failure, overall and event-free survival, and adverse events were assessed. An analysis of molecular response at 12 months was planned. A superior molecular response was defined as a decrease in the ratio of transcripts of the tyrosine kinase gene BCR-ABL to transcripts of ABL of 0.01% or less, corresponding to a reduction of 4 log(10) units or more from the baseline level, as assessed by means of a real-time quantitative polymerase-chain-reaction assay.
  
  
  RESULTS
  At 12 months, the rates of cytogenetic response were similar among the four groups. The rate of a superior molecular response was significantly higher among patients receiving imatinib and peginterferon alfa-2a (30%) than among patients receiving 400 mg of imatinib alone (14%) (P=0.001). The rate was significantly higher among patients treated for more than 12 months than among those treated for 12 months or less. Gastrointestinal events were more frequent among patients receiving cytarabine, whereas rash and depression were more frequent among patients receiving peginterferon alfa-2a.
  
  
  CONCLUSIONS
  As compared with other treatments, the addition of peginterferon alfa-2a to imatinib therapy resulted in significantly higher rates of molecular response in patients with chronic-phase CML. (Funded by the French Ministry of Health and others; ClinicalTrials.gov number, NCT00219739.).
authors.affiliation: Laboratoire d'Hématologie, Centre Hospitalier Universitaire de Lille, and INSERM Unité 837, Lille, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Preudhomme
authors.forename: Joëlle
authors.initials: J
authors.lastname: Guilhot
authors.forename: Franck Emmanuel
authors.initials: FE
authors.lastname: Nicolini
authors.forename: Agnès
authors.initials: A
authors.lastname: Guerci-Bresler
authors.forename: Françoise
authors.initials: F
authors.lastname: Rigal-Huguet
authors.forename: Frederic
authors.initials: F
authors.lastname: Maloisel
authors.forename: Valérie
authors.initials: V
authors.lastname: Coiteux
authors.forename: Martine
authors.initials: M
authors.lastname: Gardembas
authors.forename: Christian
authors.initials: C
authors.lastname: Berthou
authors.forename: Anne
authors.initials: A
authors.lastname: Vekhoff
authors.forename: Delphine
authors.initials: D
authors.lastname: Rea
authors.forename: Eric
authors.initials: E
authors.lastname: Jourdan
authors.forename: Christian
authors.initials: C
authors.lastname: Allard
authors.forename: Alain
authors.initials: A
authors.lastname: Delmer
authors.forename: Philippe
authors.initials: P
authors.lastname: Rousselot
authors.forename: Laurence
authors.initials: L
authors.lastname: Legros
authors.forename: Marc
authors.initials: M
authors.lastname: Berger
authors.forename: Selim
authors.initials: S
authors.lastname: Corm
authors.forename: Gabriel
authors.initials: G
authors.lastname: Etienne
authors.forename: Catherine
authors.initials: C
authors.lastname: Roche-Lestienne
authors.forename: Virginie
authors.initials: V
authors.lastname: Eclache
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Mahon
authors.forename: François
authors.initials: F
authors.lastname: Guilhot
mesh_terms: D000328:Adult; D000740:Anemia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000032:analysis / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects; D016315:Proto-Oncogene Proteins c-abl / Q000032:analysis / Q000235:genetics; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D012334:RNA, Neoplasm / Q000032:analysis; D011994:Recombinant Proteins; D012074:Remission Induction; D013234:Stem Cells / Q000187:drug effects; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000139:chemically induced; D014158:Transcription, Genetic; D016896:Treatment Outcome
chemical_list: D001549:Benzamides; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D010879:Piperazines; D011743:Pyrimidines; D012334:RNA, Neoplasm; D011994:Recombinant Proteins; D003561:Cytarabine; D011092:Polyethylene Glycols; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; D016315:Proto-Oncogene Proteins c-abl; C100416:peginterferon alfa-2a