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.

1 Medizinische Klinik Klinikum Bremen Mitte Bremen Germany

2 Medizinische Klinik und Poliklinik Universitätsklinikum Schleswig Holstein Kiel Germany

2 Medizinische Klinik Universitätsklinikum Eppendorf Hamburg Germany

3 Medizinische Klinik Medizinische Fakultät Mannheim Universität Heidelberg Mannheim Germany

Ambulante Hämatologie und Onkologie Bonn Germany

Barmherzige Brüder Regensburg Germany

Caritas Krankenhaus Lebach Germany

Charitè Berlin Germany

Diakonie Schwäbisch Hall Germany

Ev Krankenhaus Hamm Germany

Hämatologische Onkologische Schwerpunktpraxis Würzburg Germany

IBE Universität München Munich Germany

Innere Medizin 1 Universitätsklinikum Freiburg Germany

Inselspital Bern Switzerland

Institut für Humangenetik MHH Hanover Germany

Internistische Schwerpunktpraxis Erlangen Germany

Kantonsspital Aarau Switzerland

Klinik 1 für Innere Medizin Universitätsklinikum Köln Germany

Klinik für Hämatologie und medizinische Onkologie Universitätsmedizin Göttingen Germany

Klinik für Innere Medizin 1 Universität des Saarlandes Homburg Germany

Klinik für Innere Medizin 2 Universitätsklinikum Jena Germany

Klinik für innere Medizin 3 Chemnitz Germany

Klinik für Innere Medizin 3 Universitätsklinikum Ulm Germany

Klinik für Innere Medizin 3 Westpfalz Klinikum Kaiserslautern Germany

Klinik für innere Medizin Universitätsklinikum Marburg Germany

Klinik für Knochenmarktransplantation Essen Germany

Klinik für Onkologie und Hämatologie Oldenburg Germany

Klinik und Poliklinik für Innere Medizin 3 Universitätsklinikum Regensburg Germany

Klinikum Schwabing Munich Germany

Masaryk University Hospital Brno Czech Republic

Medizinische Abteilung 2 Universitätsklinikum Tübingen Germany

Medizinische Klinik 2 Herford Germany

Medizinische Klinik 3 Städtisches Klinikum Karlsruhe Germany

Medizinische Klinik 3 Universität Bonn Germany

Medizinische Klinik 3 Universität München Munich Germany

Medizinische Klinik 5 Klinikum Nürnberg Nord Nürnberg Germany

Medizinische Klinik 5 Universität Heidelberg Heidelberg Germany

Medizinische Klinik 5 Universitätsklinikum Erlangen Germany

Medizinische Klinik A Universitätsklinikum Münster Germany

Medizinische Klinik und Poliklinik Universitätsklinikum Würzburg Germany

MLL Munich Germany

Onkologie Leer UnterEms Leer Germany

Onkologie Zentrum Ansbach Germany

Onkologische Schwerpunktpraxis Bielefeld Germany

Onkologische Schwerpunktpraxis Heilbronn Germany

Praxisklinik für Hämatologie und Onkologie Koblenz Germany

RWTH Aachen Germany

St Antonius Hospital Eschweiler Germany

St Marien Hospital Hagen Germany

St Marien Krankenhaus Siegen Germany

Stauferklinikum Schwäbisch Gmünd Mutlangen Germany

Universitätsspital Basel Switzerland

Vivantes Klinikum Neukölln Berlin Germany

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Haematologica. 2019 May;104(5):862-864. doi: 10.3324/haematol.2018.214445. PubMed

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