Standard first-line therapy of chronic myeloid leukemia is treatment with imatinib. In the randomized German Chronic Myeloid Leukemia-Study IV, more potent BCR-ABL inhibition with 800 mg ('high-dose') imatinib accelerated achievement of a deep molecular remission. However, whether and when a de-escalation of the dose intensity under high-dose imatinib can be safely performed without increasing the risk of losing deep molecular response is unknown. To gain insights into this clinically relevant question, we analyzed the outcome of imatinib dose reductions from 800 mg to 400 mg daily in the Chronic Myeloid Leukemia-Study IV. Of the 422 patients that were randomized to the 800 mg arm, 68 reduced imatinib to 400 mg after they had achieved at least a stable major molecular response. Of these 68 patients, 61 (90%) maintained major molecular remission on imatinib at 400 mg. Five of the seven patients who lost major molecular remission on the imatinib standard dose regained major molecular remission while still on 400 mg imatinib. Only two of 68 patients had to switch to more potent kinase inhibition to regain major molecular remission. Importantly, the lengths of the intervals between imatinib high-dose treatment before and after achieving major molecular remission were associated with the probabilities of maintaining major molecular remission with the standard dose of imatinib. Taken together, the data support the view that a deep molecular remission achieved with high-dose imatinib can be safely maintained with standard dose in most patients. Study protocol registered at clinicaltrials.gov 00055874.

1 Medizinische Klinik Klinikum Bremen Mitte Bremen Germany

2 Medizinische Klinik und Poliklinik Universitätsklinikum Schleswig Holstein Kiel Germany

3 Medizinische Klinik Medizinische Fakultät Mannheim University Heidelberg Mannheim Germany

Ambulante Hämatologie und Onkologie Bonn Germany

Barmherzige Brüder Regensburg Germany

Caritas Krankenhaus Lebach Germany

Comprehensive Cancer Center Mainfranken und Medizinische Klinik 2 Zentrum für Innere Medizin Würzburg Germany

Diakonie Schwäbisch Hall Germany

Ev Krankenhaus Hamm Germany

Hämatologische Onkologische Schwerpunktpraxis Würzburg Germany

Hematology Medical Oncology Kaiserslautern Germany

Innere Medizin 1 Universitätsklinikum Freiburg Germany

Inselspital Bern Switzerland

Institut für Humangenetik MHH Hannover Germany

Institut für Medizinische Informationsverarbeitung Biometrie und Epidemiologie Ludwig Maximilians Universität München Munich 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 2 Hämatologie Onkologie und Palliativmedizin Vivantes Klinikum Neukölln Berlin Germany

Klinik für Innere Medizin 2 Hämatologie und Internistische Onkologie Jena Germany

Klinik für Innere Medizin 3 Chemnitz Germany

Klinik für Innere Medizin 3 Universitätsklinikum Ulm Germany

Klinik für Knochenmarktransplantation Essen 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 Germany

Medizinische Klinik 5 Klinikum Nürnberg Nord Germany

Medizinische Klinik 5 Universität Heidelberg Germany

Medizinische Klinik 5 Universitätsklinikum Erlangen Germany

Medizinische Klinik A Universitätsklinikum Münster Germany

Medizinische Klinik Universitätsklinikum Eppendorf Hamburg Germany

MLL Munich Germany

Onkologie Leer Unter Ems 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

Universitätsklinik für Onkologie und Hämatologie Oldenburg Germany

Universitätsklinikum Gießen und Marburg Campus Marburg Klinik für Hämatologie Onkologie und Immunologie Philipps Universität Marburg Germany

Universitätsspital Basel Switzerland

Comment In

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

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