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Chronic Myeloproliferative Neoplasias

Safety and efficacy of imatinib in CML over a period of 10 years: data from the randomized CML-study IV

Leukemia volume 29, pages 1123–1132 (2015)Cite this article

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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 MR5, 72% MR4.5, 81% MR4, 89% major molecular remission and 92% MR2 (molecular equivalent to complete cytogenetic remission). All response levels were reached faster with IM800 mg except MR5. 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.

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Acknowledgements

The CML IV study was supported by the Deutsche Krebshilfe (Nr. 106642); Deutsches Kompetenznetz für Akute und Chronische Leukämien (BMBF 01GI0270); Deutsche José-Carreras Leukämiestiftung (DJCLS H09/01 f, H06/04v, H03/01, R05/23); European LeukemiaNet (LSHC-CT-2004-503216); Novartis, Nürnberg; Roche, Grenzach-Wyhlen; and Essex Pharma, Munich, all in Germany. We thank Elke Matzat, Andrea Elett, Regina Pleil-Lösch, Inge Stalljann, Gabriele Bartsch, Uwe Böhm, Sabine Dean and all participating investigators with their teams for their contributions.

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Authors and Affiliations

  1. III. Medizinische Klinik, Medizinische Fakultät Mannheim, Universität Heidelberg, Mannheim, Germany

    L Kalmanti, S Saussele, M C Müller, C T Dietz, L Heinrich, B Hanfstein, U Proetel, A Fabarius, S Rinaldetti & R Hehlmann

  2. Institut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie, Ludwig-Maximilians-Universität, München, Germany

    M Lauseker, M Pfirrmann & J Hasford

  3. Medizinische Klinik 5, Universitätsklinikum, Erlangen, Germany

    S W Krause

  4. Medizinische Klinik V, Universitätsklinikum, Heidelberg, Germany

    J Dengler

  5. Medizinische Klinik 5, Klinikum Nürnberg Nord, Nürnberg, Germany

    C Falge

  6. Universitätsklinik für Hämatologie, Inselspital, Bern, Switzerland

    E Oppliger-Leibundgut

  7. Klinik für Innere Medizin, Universitätsklinikum, Marburg, Germany

    A Burchert & A Neubauer

  8. Medizinische Klinik II, Universitätsklinikum, Tübingen, Germany

    L Kanz

  9. Klinik für Innere Medizin III, Universitätsklinikum, Ulm, Germany

    F Stegelmann

  10. Innere Medizin I, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany

    M Pfreundschuh

  11. Medizinische Klinik und Poliklinik III, Ludwig-Maximilians-Universität, München, Germany

    K Spiekermann

  12. Klinik I für Innere Medizin, Universitätsklinikum, Köln, Germany

    C Scheid

  13. Klinik für Innere Medizin II, Universitätsklinikum, Jena, Germany

    A Hochhaus

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Competing interests

SS has received honoraria from Novartis, Bristol-Myers Squibb (BMS), Pfizer and research funding from Novartis and BMS; MCM honoraria and research funding from Novartis, BMS, ARIAD and Pfizer; BH honoraria from BMS and research funding from Novartis; AN honoraria from Medupdate; CS honoraria for consulting from Novartis; MP honoraria from BMS and consultancy from Novartis; AH honoraria from Novartis, BMS,ARIAD, consultancy from Novartis and research funding from Novartis, ARIAD and Pfizer and RH has research funding from Novartis and BMS. The remaining authors declare no conflicts of interest.

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Kalmanti, L., Saussele, S., Lauseker, M. et al. Safety and efficacy of imatinib in CML over a period of 10 years: data from the randomized CML-study IV. Leukemia 29, 1123–1132 (2015). https://doi.org/10.1038/leu.2015.36

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