title: Long-Term Outcomes of Imatinib Treatment for Chronic Myeloid Leukemia.
abstract: Imatinib, a selective BCR-ABL1 kinase inhibitor, improved the prognosis for patients with chronic myeloid leukemia (CML). We conducted efficacy and safety analyses on the basis of more than 10 years of follow-up in patients with CML who were treated with imatinib as initial therapy.
  
  
  
  In this open-label, multicenter trial with crossover design, we randomly assigned patients with newly diagnosed CML in the chronic phase to receive either imatinib or interferon alfa plus cytarabine. Long-term analyses included overall survival, response to treatment, and serious adverse events.
  
  
  
  The median follow-up was 10.9 years. Given the high rate of crossover among patients who had been randomly assigned to receive interferon alfa plus cytarabine (65.6%) and the short duration of therapy before crossover in these patients (median, 0.8 years), the current analyses focused on patients who had been randomly assigned to receive imatinib. Among the patients in the imatinib group, the estimated overall survival rate at 10 years was 83.3%. Approximately half the patients (48.3%) who had been randomly assigned to imatinib completed study treatment with imatinib, and 82.8% had a complete cytogenetic response. Serious adverse events that were considered by the investigators to be related to imatinib were uncommon and most frequently occurred during the first year of treatment.
  
  
  
  Almost 11 years of follow-up showed that the efficacy of imatinib persisted over time and that long-term administration of imatinib was not associated with unacceptable cumulative or late toxic effects. (Funded by Novartis Pharmaceuticals; IRIS ClinicalTrials.gov numbers, NCT00006343 and NCT00333840 .).
authors.affiliation: From Abteilung Hämatologie-Onkologie, Universitätsklinikum Jena, Jena, Germany (A.H.); the Department of Medicine, University of Chicago, Chicago (R.A.L.); INSERM Centre d'Investigation Clinique 1402, Centre Hospitalier Universitaire de Poitiers, Poitiers, France (F.G.); Fred Hutchinson Cancer Research Center, Seattle (J.P.R.); Centre for Cancer Biology, SA Pathology, University of South Australia and University of Adelaide (S.B.), and the South Australian Health and Medical Research Institute and University of Adelaide (T.P.H.), Adelaide, SA, Australia; University of Bologna, Bologna, Italy (M.B.); the University of Utah Huntsman Cancer Institute, Salt Lake City (M.W.D.); the Hematology Department, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona (F.C.); Novartis, Basel, Switzerland (S.F., C.-E.O., H.D.M.); M.D. Anderson Cancer Center, Houston (H.K.); the University of Newcastle, Newcastle, United Kingdom (S.G.O.); and Knight Cancer Institute, Oregon Health and Science University and Howard Hughes Medical Institute, Portland (B.J.D.).
authors.forename: Andreas
authors.initials: A
authors.lastname: Hochhaus
authors.affiliation: From Abteilung Hämatologie-Onkologie, Universitätsklinikum Jena, Jena, Germany (A.H.); the Department of Medicine, University of Chicago, Chicago (R.A.L.); INSERM Centre d'Investigation Clinique 1402, Centre Hospitalier Universitaire de Poitiers, Poitiers, France (F.G.); Fred Hutchinson Cancer Research Center, Seattle (J.P.R.); Centre for Cancer Biology, SA Pathology, University of South Australia and University of Adelaide (S.B.), and the South Australian Health and Medical Research Institute and University of Adelaide (T.P.H.), Adelaide, SA, Australia; University of Bologna, Bologna, Italy (M.B.); the University of Utah Huntsman Cancer Institute, Salt Lake City (M.W.D.); the Hematology Department, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona (F.C.); Novartis, Basel, Switzerland (S.F., C.-E.O., H.D.M.); M.D. Anderson Cancer Center, Houston (H.K.); the University of Newcastle, Newcastle, United Kingdom (S.G.O.); and Knight Cancer Institute, Oregon Health and Science University and Howard Hughes Medical Institute, Portland (B.J.D.).
authors.forename: Richard A
authors.initials: RA
authors.lastname: Larson
authors.affiliation: From Abteilung Hämatologie-Onkologie, Universitätsklinikum Jena, Jena, Germany (A.H.); the Department of Medicine, University of Chicago, Chicago (R.A.L.); INSERM Centre d'Investigation Clinique 1402, Centre Hospitalier Universitaire de Poitiers, Poitiers, France (F.G.); Fred Hutchinson Cancer Research Center, Seattle (J.P.R.); Centre for Cancer Biology, SA Pathology, University of South Australia and University of Adelaide (S.B.), and the South Australian Health and Medical Research Institute and University of Adelaide (T.P.H.), Adelaide, SA, Australia; University of Bologna, Bologna, Italy (M.B.); the University of Utah Huntsman Cancer Institute, Salt Lake City (M.W.D.); the Hematology Department, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona (F.C.); Novartis, Basel, Switzerland (S.F., C.-E.O., H.D.M.); M.D. Anderson Cancer Center, Houston (H.K.); the University of Newcastle, Newcastle, United Kingdom (S.G.O.); and Knight Cancer Institute, Oregon Health and Science University and Howard Hughes Medical Institute, Portland (B.J.D.).
authors.forename: François
authors.initials: F
authors.lastname: Guilhot
authors.affiliation: From Abteilung Hämatologie-Onkologie, Universitätsklinikum Jena, Jena, Germany (A.H.); the Department of Medicine, University of Chicago, Chicago (R.A.L.); INSERM Centre d'Investigation Clinique 1402, Centre Hospitalier Universitaire de Poitiers, Poitiers, France (F.G.); Fred Hutchinson Cancer Research Center, Seattle (J.P.R.); Centre for Cancer Biology, SA Pathology, University of South Australia and University of Adelaide (S.B.), and the South Australian Health and Medical Research Institute and University of Adelaide (T.P.H.), Adelaide, SA, Australia; University of Bologna, Bologna, Italy (M.B.); the University of Utah Huntsman Cancer Institute, Salt Lake City (M.W.D.); the Hematology Department, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona (F.C.); Novartis, Basel, Switzerland (S.F., C.-E.O., H.D.M.); M.D. Anderson Cancer Center, Houston (H.K.); the University of Newcastle, Newcastle, United Kingdom (S.G.O.); and Knight Cancer Institute, Oregon Health and Science University and Howard Hughes Medical Institute, Portland (B.J.D.).
authors.forename: Jerald P
authors.initials: JP
authors.lastname: Radich
authors.affiliation: From Abteilung Hämatologie-Onkologie, Universitätsklinikum Jena, Jena, Germany (A.H.); the Department of Medicine, University of Chicago, Chicago (R.A.L.); INSERM Centre d'Investigation Clinique 1402, Centre Hospitalier Universitaire de Poitiers, Poitiers, France (F.G.); Fred Hutchinson Cancer Research Center, Seattle (J.P.R.); Centre for Cancer Biology, SA Pathology, University of South Australia and University of Adelaide (S.B.), and the South Australian Health and Medical Research Institute and University of Adelaide (T.P.H.), Adelaide, SA, Australia; University of Bologna, Bologna, Italy (M.B.); the University of Utah Huntsman Cancer Institute, Salt Lake City (M.W.D.); the Hematology Department, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona (F.C.); Novartis, Basel, Switzerland (S.F., C.-E.O., H.D.M.); M.D. Anderson Cancer Center, Houston (H.K.); the University of Newcastle, Newcastle, United Kingdom (S.G.O.); and Knight Cancer Institute, Oregon Health and Science University and Howard Hughes Medical Institute, Portland (B.J.D.).
authors.forename: Susan
authors.initials: S
authors.lastname: Branford
authors.affiliation: From Abteilung Hämatologie-Onkologie, Universitätsklinikum Jena, Jena, Germany (A.H.); the Department of Medicine, University of Chicago, Chicago (R.A.L.); INSERM Centre d'Investigation Clinique 1402, Centre Hospitalier Universitaire de Poitiers, Poitiers, France (F.G.); Fred Hutchinson Cancer Research Center, Seattle (J.P.R.); Centre for Cancer Biology, SA Pathology, University of South Australia and University of Adelaide (S.B.), and the South Australian Health and Medical Research Institute and University of Adelaide (T.P.H.), Adelaide, SA, Australia; University of Bologna, Bologna, Italy (M.B.); the University of Utah Huntsman Cancer Institute, Salt Lake City (M.W.D.); the Hematology Department, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona (F.C.); Novartis, Basel, Switzerland (S.F., C.-E.O., H.D.M.); M.D. Anderson Cancer Center, Houston (H.K.); the University of Newcastle, Newcastle, United Kingdom (S.G.O.); and Knight Cancer Institute, Oregon Health and Science University and Howard Hughes Medical Institute, Portland (B.J.D.).
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Hughes
authors.affiliation: From Abteilung Hämatologie-Onkologie, Universitätsklinikum Jena, Jena, Germany (A.H.); the Department of Medicine, University of Chicago, Chicago (R.A.L.); INSERM Centre d'Investigation Clinique 1402, Centre Hospitalier Universitaire de Poitiers, Poitiers, France (F.G.); Fred Hutchinson Cancer Research Center, Seattle (J.P.R.); Centre for Cancer Biology, SA Pathology, University of South Australia and University of Adelaide (S.B.), and the South Australian Health and Medical Research Institute and University of Adelaide (T.P.H.), Adelaide, SA, Australia; University of Bologna, Bologna, Italy (M.B.); the University of Utah Huntsman Cancer Institute, Salt Lake City (M.W.D.); the Hematology Department, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona (F.C.); Novartis, Basel, Switzerland (S.F., C.-E.O., H.D.M.); M.D. Anderson Cancer Center, Houston (H.K.); the University of Newcastle, Newcastle, United Kingdom (S.G.O.); and Knight Cancer Institute, Oregon Health and Science University and Howard Hughes Medical Institute, Portland (B.J.D.).
authors.forename: Michele
authors.initials: M
authors.lastname: Baccarani
authors.affiliation: From Abteilung Hämatologie-Onkologie, Universitätsklinikum Jena, Jena, Germany (A.H.); the Department of Medicine, University of Chicago, Chicago (R.A.L.); INSERM Centre d'Investigation Clinique 1402, Centre Hospitalier Universitaire de Poitiers, Poitiers, France (F.G.); Fred Hutchinson Cancer Research Center, Seattle (J.P.R.); Centre for Cancer Biology, SA Pathology, University of South Australia and University of Adelaide (S.B.), and the South Australian Health and Medical Research Institute and University of Adelaide (T.P.H.), Adelaide, SA, Australia; University of Bologna, Bologna, Italy (M.B.); the University of Utah Huntsman Cancer Institute, Salt Lake City (M.W.D.); the Hematology Department, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona (F.C.); Novartis, Basel, Switzerland (S.F., C.-E.O., H.D.M.); M.D. Anderson Cancer Center, Houston (H.K.); the University of Newcastle, Newcastle, United Kingdom (S.G.O.); and Knight Cancer Institute, Oregon Health and Science University and Howard Hughes Medical Institute, Portland (B.J.D.).
authors.forename: Michael W
authors.initials: MW
authors.lastname: Deininger
authors.affiliation: From Abteilung Hämatologie-Onkologie, Universitätsklinikum Jena, Jena, Germany (A.H.); the Department of Medicine, University of Chicago, Chicago (R.A.L.); INSERM Centre d'Investigation Clinique 1402, Centre Hospitalier Universitaire de Poitiers, Poitiers, France (F.G.); Fred Hutchinson Cancer Research Center, Seattle (J.P.R.); Centre for Cancer Biology, SA Pathology, University of South Australia and University of Adelaide (S.B.), and the South Australian Health and Medical Research Institute and University of Adelaide (T.P.H.), Adelaide, SA, Australia; University of Bologna, Bologna, Italy (M.B.); the University of Utah Huntsman Cancer Institute, Salt Lake City (M.W.D.); the Hematology Department, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona (F.C.); Novartis, Basel, Switzerland (S.F., C.-E.O., H.D.M.); M.D. Anderson Cancer Center, Houston (H.K.); the University of Newcastle, Newcastle, United Kingdom (S.G.O.); and Knight Cancer Institute, Oregon Health and Science University and Howard Hughes Medical Institute, Portland (B.J.D.).
authors.forename: Francisco
authors.initials: F
authors.lastname: Cervantes
authors.affiliation: From Abteilung Hämatologie-Onkologie, Universitätsklinikum Jena, Jena, Germany (A.H.); the Department of Medicine, University of Chicago, Chicago (R.A.L.); INSERM Centre d'Investigation Clinique 1402, Centre Hospitalier Universitaire de Poitiers, Poitiers, France (F.G.); Fred Hutchinson Cancer Research Center, Seattle (J.P.R.); Centre for Cancer Biology, SA Pathology, University of South Australia and University of Adelaide (S.B.), and the South Australian Health and Medical Research Institute and University of Adelaide (T.P.H.), Adelaide, SA, Australia; University of Bologna, Bologna, Italy (M.B.); the University of Utah Huntsman Cancer Institute, Salt Lake City (M.W.D.); the Hematology Department, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona (F.C.); Novartis, Basel, Switzerland (S.F., C.-E.O., H.D.M.); M.D. Anderson Cancer Center, Houston (H.K.); the University of Newcastle, Newcastle, United Kingdom (S.G.O.); and Knight Cancer Institute, Oregon Health and Science University and Howard Hughes Medical Institute, Portland (B.J.D.).
authors.forename: Satoko
authors.initials: S
authors.lastname: Fujihara
authors.affiliation: From Abteilung Hämatologie-Onkologie, Universitätsklinikum Jena, Jena, Germany (A.H.); the Department of Medicine, University of Chicago, Chicago (R.A.L.); INSERM Centre d'Investigation Clinique 1402, Centre Hospitalier Universitaire de Poitiers, Poitiers, France (F.G.); Fred Hutchinson Cancer Research Center, Seattle (J.P.R.); Centre for Cancer Biology, SA Pathology, University of South Australia and University of Adelaide (S.B.), and the South Australian Health and Medical Research Institute and University of Adelaide (T.P.H.), Adelaide, SA, Australia; University of Bologna, Bologna, Italy (M.B.); the University of Utah Huntsman Cancer Institute, Salt Lake City (M.W.D.); the Hematology Department, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona (F.C.); Novartis, Basel, Switzerland (S.F., C.-E.O., H.D.M.); M.D. Anderson Cancer Center, Houston (H.K.); the University of Newcastle, Newcastle, United Kingdom (S.G.O.); and Knight Cancer Institute, Oregon Health and Science University and Howard Hughes Medical Institute, Portland (B.J.D.).
authors.forename: Christine-Elke
authors.initials: CE
authors.lastname: Ortmann
authors.affiliation: From Abteilung Hämatologie-Onkologie, Universitätsklinikum Jena, Jena, Germany (A.H.); the Department of Medicine, University of Chicago, Chicago (R.A.L.); INSERM Centre d'Investigation Clinique 1402, Centre Hospitalier Universitaire de Poitiers, Poitiers, France (F.G.); Fred Hutchinson Cancer Research Center, Seattle (J.P.R.); Centre for Cancer Biology, SA Pathology, University of South Australia and University of Adelaide (S.B.), and the South Australian Health and Medical Research Institute and University of Adelaide (T.P.H.), Adelaide, SA, Australia; University of Bologna, Bologna, Italy (M.B.); the University of Utah Huntsman Cancer Institute, Salt Lake City (M.W.D.); the Hematology Department, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona (F.C.); Novartis, Basel, Switzerland (S.F., C.-E.O., H.D.M.); M.D. Anderson Cancer Center, Houston (H.K.); the University of Newcastle, Newcastle, United Kingdom (S.G.O.); and Knight Cancer Institute, Oregon Health and Science University and Howard Hughes Medical Institute, Portland (B.J.D.).
authors.forename: Hans D
authors.initials: HD
authors.lastname: Menssen
authors.affiliation: From Abteilung Hämatologie-Onkologie, Universitätsklinikum Jena, Jena, Germany (A.H.); the Department of Medicine, University of Chicago, Chicago (R.A.L.); INSERM Centre d'Investigation Clinique 1402, Centre Hospitalier Universitaire de Poitiers, Poitiers, France (F.G.); Fred Hutchinson Cancer Research Center, Seattle (J.P.R.); Centre for Cancer Biology, SA Pathology, University of South Australia and University of Adelaide (S.B.), and the South Australian Health and Medical Research Institute and University of Adelaide (T.P.H.), Adelaide, SA, Australia; University of Bologna, Bologna, Italy (M.B.); the University of Utah Huntsman Cancer Institute, Salt Lake City (M.W.D.); the Hematology Department, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona (F.C.); Novartis, Basel, Switzerland (S.F., C.-E.O., H.D.M.); M.D. Anderson Cancer Center, Houston (H.K.); the University of Newcastle, Newcastle, United Kingdom (S.G.O.); and Knight Cancer Institute, Oregon Health and Science University and Howard Hughes Medical Institute, Portland (B.J.D.).
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.affiliation: From Abteilung Hämatologie-Onkologie, Universitätsklinikum Jena, Jena, Germany (A.H.); the Department of Medicine, University of Chicago, Chicago (R.A.L.); INSERM Centre d'Investigation Clinique 1402, Centre Hospitalier Universitaire de Poitiers, Poitiers, France (F.G.); Fred Hutchinson Cancer Research Center, Seattle (J.P.R.); Centre for Cancer Biology, SA Pathology, University of South Australia and University of Adelaide (S.B.), and the South Australian Health and Medical Research Institute and University of Adelaide (T.P.H.), Adelaide, SA, Australia; University of Bologna, Bologna, Italy (M.B.); the University of Utah Huntsman Cancer Institute, Salt Lake City (M.W.D.); the Hematology Department, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona (F.C.); Novartis, Basel, Switzerland (S.F., C.-E.O., H.D.M.); M.D. Anderson Cancer Center, Houston (H.K.); the University of Newcastle, Newcastle, United Kingdom (S.G.O.); and Knight Cancer Institute, Oregon Health and Science University and Howard Hughes Medical Institute, Portland (B.J.D.).
authors.forename: Stephen G
authors.initials: SG
authors.lastname: O'Brien
authors.affiliation: From Abteilung Hämatologie-Onkologie, Universitätsklinikum Jena, Jena, Germany (A.H.); the Department of Medicine, University of Chicago, Chicago (R.A.L.); INSERM Centre d'Investigation Clinique 1402, Centre Hospitalier Universitaire de Poitiers, Poitiers, France (F.G.); Fred Hutchinson Cancer Research Center, Seattle (J.P.R.); Centre for Cancer Biology, SA Pathology, University of South Australia and University of Adelaide (S.B.), and the South Australian Health and Medical Research Institute and University of Adelaide (T.P.H.), Adelaide, SA, Australia; University of Bologna, Bologna, Italy (M.B.); the University of Utah Huntsman Cancer Institute, Salt Lake City (M.W.D.); the Hematology Department, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona (F.C.); Novartis, Basel, Switzerland (S.F., C.-E.O., H.D.M.); M.D. Anderson Cancer Center, Houston (H.K.); the University of Newcastle, Newcastle, United Kingdom (S.G.O.); and Knight Cancer Institute, Oregon Health and Science University and Howard Hughes Medical Institute, Portland (B.J.D.).
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Druker
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D018592:Cross-Over Studies; D003561:Cytarabine / Q000627:therapeutic use; D020732:Cytogenetic Analysis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000068877:Imatinib Mesylate / Q000009:adverse effects / Q000627:therapeutic use*; D057194:Intention to Treat Analysis; D016898:Interferon-alpha / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D016898:Interferon-alpha; D047428:Protein Kinase Inhibitors; D003561:Cytarabine; D000068877:Imatinib Mesylate