title: Safety and efficacy of imatinib in CML over a period of 10 years: data from the randomized CML-study IV.
abstract: Tyrosine kinase inhibitors (TKI) have changed the natural course of chronic myeloid leukemia (CML). With the advent of second-generation TKI safety and efficacy issues have gained interest. The randomized CML - Study IV was used for a long-term evaluation of imatinib (IM). 1503 patients have received IM, 1379 IM monotherapy. After a median observation of 7.1 years, 965 patients (64%) still received IM. At 10 years, progression-free survival was 82%, overall survival 84%, 59% achieved MR(5), 72% MR(4.5), 81% MR(4), 89% major molecular remission and 92% MR(2) (molecular equivalent to complete cytogenetic remission). All response levels were reached faster with IM800 mg except MR(5). Eight-year probabilities of adverse drug reactions (ADR) were 76%, of grades 3-4 22%, of non-hematologic 73%, and of hematologic 28%. More ADR were observed with IM800 mg and IM400 mg plus interferon α (IFN). Most patients had their first ADR early with decreasing frequency later on. No new late toxicity was observed. ADR to IM are frequent, but mostly mild and manageable, also with IM 800 mg and IM 400 mg+IFN. The deep molecular response rates indicate that most patients are candidates for IM discontinuation. After 10 years, IM continues to be an excellent initial choice for most patients with CML.
authors: III. Medizinische Klinik, Medizinische Fakultät Mannheim, Universität Heidelberg, Mannheim, Germany.
authors: L
authors: L
authors: Kalmanti
authors: III. Medizinische Klinik, Medizinische Fakultät Mannheim, Universität Heidelberg, Mannheim, Germany.
authors: S
authors: S
authors: Saussele
authors: Institut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie, Ludwig-Maximilians-Universität, München, Germany.
authors: M
authors: M
authors: Lauseker
authors: III. Medizinische Klinik, Medizinische Fakultät Mannheim, Universität Heidelberg, Mannheim, Germany.
authors: M C
authors: MC
authors: Müller
authors: III. Medizinische Klinik, Medizinische Fakultät Mannheim, Universität Heidelberg, Mannheim, Germany.
authors: C T
authors: CT
authors: Dietz
authors: III. Medizinische Klinik, Medizinische Fakultät Mannheim, Universität Heidelberg, Mannheim, Germany.
authors: L
authors: L
authors: Heinrich
authors: III. Medizinische Klinik, Medizinische Fakultät Mannheim, Universität Heidelberg, Mannheim, Germany.
authors: B
authors: B
authors: Hanfstein
authors: III. Medizinische Klinik, Medizinische Fakultät Mannheim, Universität Heidelberg, Mannheim, Germany.
authors: U
authors: U
authors: Proetel
authors: III. Medizinische Klinik, Medizinische Fakultät Mannheim, Universität Heidelberg, Mannheim, Germany.
authors: A
authors: A
authors: Fabarius
authors: Medizinische Klinik 5, Universitätsklinikum, Erlangen, Germany.
authors: S W
authors: SW
authors: Krause
authors: III. Medizinische Klinik, Medizinische Fakultät Mannheim, Universität Heidelberg, Mannheim, Germany.
authors: S
authors: S
authors: Rinaldetti
authors: Medizinische Klinik V, Universitätsklinikum, Heidelberg, Germany.
authors: J
authors: J
authors: Dengler
authors: Medizinische Klinik 5, Klinikum Nürnberg Nord, Nürnberg, Germany.
authors: C
authors: C
authors: Falge
authors: Universitätsklinik für Hämatologie, Inselspital, Bern, Switzerland.
authors: E
authors: E
authors: Oppliger-Leibundgut
authors: Klinik für Innere Medizin, Universitätsklinikum, Marburg, Germany.
authors: A
authors: A
authors: Burchert
authors: Klinik für Innere Medizin, Universitätsklinikum, Marburg, Germany.
authors: A
authors: A
authors: Neubauer
authors: Medizinische Klinik II, Universitätsklinikum, Tübingen, Germany.
authors: L
authors: L
authors: Kanz
authors: Klinik für Innere Medizin III, Universitätsklinikum, Ulm, Germany.
authors: F
authors: F
authors: Stegelmann
authors: Innere Medizin I, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany.
authors: M
authors: M
authors: Pfreundschuh
authors: Medizinische Klinik und Poliklinik III, Ludwig-Maximilians-Universität, München, Germany.
authors: K
authors: K
authors: Spiekermann
authors: Klinik I für Innere Medizin, Universitätsklinikum, Köln, Germany.
authors: C
authors: C
authors: Scheid
authors: Institut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie, Ludwig-Maximilians-Universität, München, Germany.
authors: M
authors: M
authors: Pfirrmann
authors: Klinik für Innere Medizin II, Universitätsklinikum, Jena, Germany.
authors: A
authors: A
authors: Hochhaus
authors: Institut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie, Ludwig-Maximilians-Universität, München, Germany.
authors: J
authors: J
authors: Hasford
authors: III. Medizinische Klinik, Medizinische Fakultät Mannheim, Universität Heidelberg, Mannheim, Germany.
authors: R
authors: R
authors: Hehlmann
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001549:Benzamides / Q000008:administration & dosage* / Q000009:adverse effects; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000068877:Imatinib Mesylate; D016898:Interferon-alpha / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D016898:Interferon-alpha; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl