Assessment of imatinib as first-line treatment of chronic myeloid leukemia: 10-year survival results of the randomized CML study IV and impact of non-CML determinants

Hehlmann R, Lauseker M, Saussele S, Pfirrmann M, Krause S, Kolb HJ, Neubauer A, Hossfeld DK, Nerl C, Gratwohl A, Baerlocher GM, Heim D, Bruemmendorf TH, Fabarius A, Haferlach C, Schlegelberger B, Mueller MC, Jeromin S, Proetel U, Kohlbrenner K, Voskanyan A, Rinaldetti S, Seifarth W, Spiess B, Balleisen L, Goebeler MC, Haenel M, Ho A, Dengler J, Falge C, Kanz L, Kremers S, Burchert A, Kneba M, Stegelmann F, Koehne CA, Lindemann HW, Waller CF, Pfreundschuh M, Spiekermann K, Berdel WE, Mueller L, Edinger M, Mayer J, Beelen DW, Bentz M, Link H, Hertenstein B, Fuchs R, Wernli M, Schlegel F, Schlag R, De Wit M, Truemper L, Hebart H, Hahn M, Thomalla J, Scheid C, Schafhausen P, Verbeek W, Eckart MJ, Gassmann W, Pezzutto A, Schenk M, Brossart P, Geer T, Bildat S, Schaefer E, Hochhaus A, Hasford J (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Book Volume: 31

Pages Range: 2398-2406

Journal Issue: 11

DOI: 10.1038/leu.2017.253

Abstract

Chronic myeloid leukemia (CML)-study IV was designed to explore whether treatment with imatinib (IM) at 400 mg/day (n=400) could be optimized by doubling the dose (n=420), adding interferon (IFN) (n=430) or cytarabine (n=158) or using IM after IFN-failure (n=128). From July 2002 to March 2012, 1551 newly diagnosed patients in chronic phase were randomized into a 5-arm study. The study was powered to detect a survival difference of 5% at 5 years. After a median observation time of 9.5 years, 10-year overall survival was 82%, 10-year progression-free survival was 80% and 10-year relative survival was 92%. Survival between IM400 mg and any experimental arm was not different. In a multivariate analysis, risk group, major-route chromosomal aberrations, comorbidities, smoking and treatment center (academic vs other) influenced survival significantly, but not any form of treatment optimization. Patients reaching the molecular response milestones at 3, 6 and 12 months had a significant survival advantage. For responders, monotherapy with IM400 mg provides a close to normal life expectancy independent of the time to response. Survival is more determined by patients' and disease factors than by initial treatment selection. Although improvements are also needed for refractory disease, more life-time can currently be gained by carefully addressing non-CML determinants of survival.

Authors with CRIS profile

Involved external institutions

Masaryk University Czech Republic (CZ) Onkologie Leer - Emden - Papenburg Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Ruprecht-Karls-Universität Heidelberg Germany (DE) Ludwig-Maximilians-Universität (LMU) Germany (DE) Universitätsklinikum Münster Germany (DE) Klinikum Schwabing Germany (DE) Universitätsspital Basel Switzerland (CH) Inselspital, Universitätsspital Bern Switzerland (CH) Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen Germany (DE) MLL Münchner Leukämielabor GmbH Germany (DE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Evangelisches Krankenhaus Hamm Germany (DE) Klinikum Chemnitz Germany (DE) Klinikum Nürnberg Germany (DE) Caritas-Krankenhaus Lebach Germany (DE) Universitätsklinikum Schleswig-Holstein (UKSH) Germany (DE) Klinikum Oldenburg Germany (DE) St.-Marien-Hospital Germany (DE) Universität des Saarlandes (UdS) Germany (DE) Universitätsklinikum Essen Germany (DE) Städtisches Klinikum Karlsruhe Germany (DE) Westpfalz-Klinikum Germany (DE) Klinikverbund Bremen (Gesundheit Nord) Germany (DE) St. Antonius Ziekenhuis Netherlands (NL) Onkologische Gemeinschaftspraxis Würzburg Germany (DE) Vivantes - Netzwerk für Gesundheit GmbH Germany (DE) Universitätsklinikum Göttingen Germany (DE) Stauferklinikum Schwäbisch Gmünd Germany (DE) Zentrum für ambulante Hämatologie + Onkologie Germany (DE) St. Marien-Krankenhaus Germany (DE) Charité - Universitätsmedizin Berlin Germany (DE) Krankenhaus Barmherzige Brüder Germany (DE) Universitätsklinikum Bonn Germany (DE) Diakonie Deutschland - Evangelischer Bundesverband Evangelisches Werk für Diakonie und Entwicklung e.V. Germany (DE) Klinikum Herford Germany (DE) Onkologische Schwerpunktpraxis Bielefeld Germany (DE)

How to cite

APA:

Hehlmann, R., Lauseker, M., Saussele, S., Pfirrmann, M., Krause, S., Kolb, H.J.,... Hasford, J. (2017). Assessment of imatinib as first-line treatment of chronic myeloid leukemia: 10-year survival results of the randomized CML study IV and impact of non-CML determinants. Leukemia, 31(11), 2398-2406. https://doi.org/10.1038/leu.2017.253

MLA:

Hehlmann, R., et al. "Assessment of imatinib as first-line treatment of chronic myeloid leukemia: 10-year survival results of the randomized CML study IV and impact of non-CML determinants." Leukemia 31.11 (2017): 2398-2406.

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