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Acute myeloid leukemia

Adding dasatinib to intensive treatment in core-binding factor acute myeloid leukemia—results of the AMLSG 11-08 trial

Leukemia volume 32, pages 1621–1630 (2018)Cite this article

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Abstract

In this phase Ib/IIa study (ClinicalTrials.gov Identifier: NCT00850382) of the German-Austrian AML Study Group (AMLSG) the multikinase inhibitor dasatinib was added to intensive induction and consolidation chemotherapy and administered as single agent for 1-year maintenance in first-line treatment of adult patients with core-binding factor (CBF) acute myeloid leukemia (AML). The primary combined end point in this study was safety and feasibility, and included the rates of early (ED) and hypoplastic (HD) deaths, pleural/pericardial effusion 3°/4° and liver toxicity 3°/4°, and the rate of refractory disease. Secondary end points were cumulative incidence of relapse (CIR) and death in complete remission (CID), and overall survival (OS). Eighty-nine pts [median age 49.5 years, range: 19–73 years; t(8;21), n = 37; inv (16), n = 52] were included. No unexpected excess in toxicity was observed. The rates of ED/HD and CR/CRi were 4.5% (4/89) and 94% (84/89), respectively. The 4-year estimated CIR, CID, and OS were 33.1% [95%-CI (confidence interval), 22.7–43.4%], 6.0% (95% CI, 0.9–11.2%), and 74.7% (95% CI, 66.1–84.5%), respectively. On the basis of the acceptable toxicity profile and favorable outcome in the AMLSG 11–08 trial, a confirmatory randomized phase III trial with dasatinib in adults with CBF-AML is ongoing (ClinicalTrials.gov Identifier: NCT02013648).

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Acknowledgements

This work in supported in part by grant 109675 from the Deutsche Krebshilfe. We are grateful to all members of the German-Austrian AML Study Group (AMLSG) for their participation in this study and providing patient samples; a list of participating institutions and investigators appears in the Appendix.

Authors contribution:

RFS and HD designed the study; KD, AG, HD provided administrative support; PP, RFS, DW, KD, AG, HD contributed to the data collection and interpretation; VT, GG, HD participated in interpretation of the cytogenetic results; PP, MH, VIG, F.T., MA carried out and/or interpreted the molecular analyses; DW, RFS, AB performed statistical analyses; PP, RFS, LB, MH, VIG, FT, VT, ML, WF, MRad, JK, H-AH, RG, KM, AK, UM, GH, HRS, BH, CS, GW, EL, MP, MRin, MG, TH, DK, AG, KD, HD were involved directly or indirectly in care of patients, sample procurement, or both; PP, KD, HD drafted the manuscript; and all authors agreed on the final version.

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Authors and Affiliations

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

    Peter Paschka, Richard F Schlenk, Daniela Weber, Lars Bullinger, Verena I Gaidzik, Mridul Agrawal, Veronica Teleanu, Konstanze Döhner & Hartmut Döhner

  2. Abteilung Biostatistik, Deutsches Krebsforschungszentrum, Heidelberg, Germany

    Axel Benner

  3. Klinik für Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation, Medizinische Hochschule Hannover, Hannover, Germany

    Michael Heuser, Felicitas Thol & Arnold Ganser

  4. Klinik für Innere Medizin I, Medizinische Fakultät, Universitätsklinikum Freiburg, Freiburg, Germany

    Michael Lübbert

  5. II. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany

    Walter Fiedler

  6. III. Medizinische Klinik und Poliklinik, Universitätsmedizin Mainz, Mainz, Germany

    Markus Radsak

  7. Medizinische Klinik III, Klinikum Braunschweig, Braunschweig, Germany

    Jürgen Krauter

  8. Klinik für Innere Medizin II, Universitätsklinikum Schleswig-Holstein, Kiel, Germany

    Heinz-A. Horst

  9. 3. III. Medizinische Universitätsklinik, Paracelsus Medizinische Privatuniversität Salzburg, Salzburg Cancer Research Institute, Cancer Cluster Salzburg, Salzburg, Austria

    Richard Greil

  10. Medizinische Klinik und Poliklinik III, Universitätsklinikum Bonn, Bonn, Germany

    Karin Mayer

  11. Klinik für Hämatologie, Onkologie und Klinische Immunologie, Universitätsklinikum Düsseldorf, Düsseldorf, Germany

    Andrea Kündgen

  12. Klinik für Innere Medizin III, SLK-Kliniken Heilbronn GmbH, Heilbronn, Germany

    Uwe Martens

  13. Innere Medizin V, Märkische Kliniken, Klinikum Lüdenscheid, Lüdenscheid, Germany

    Gerhard Heil

  14. Innere Medizin II, Medizinische Klinik, Universitätsklinikum Tübingen, Tübingen, Germany

    Helmut R Salih

  15. Medizinische Klinik I, Klinikum Bremen-Mitte, Bremen, Germany

    Bernd Hertenstein

  16. Klinik für Allgemeine Innere Medizin, Onkologie/Hämatologie, Gastroenterologie und Infektiologie, Klinikum Esslingen GmbH, Esslingen, Germany

    Carsten Schwänen

  17. Klinik für Hämatologie und Medizinische Onkologie, Universitätsmedizin Göttingen, Göttingen, Germany

    Gerald Wulf

  18. Klinik für Hämatologie, Onkologie und Palliativmedizin, Evangelisches Krankenhaus Hamm, Hamm, Germany

    Elisabeth Lange

  19. Innere Medizin I, Universitätsklinikum des Saarlandes, Homburg, Germany

    Michael Pfreundschuh

  20. Medizinische Klinik III, Städtisches Klinikum Karlsruhe gGmbH, Karlsruhe, Germany

    Mark Ringhoffer

  21. Interne 1—Hämato-Onkologie, Krankenhaus der Elisabethinen Linz, Linz, Austria

    Michael Girschikofsky

  22. Klinik für Hämatologie und Onkologie, Universitätsklinikum Magdeburg, Magdeburg, Germany

    Thomas Heinicke

  23. Klinik für Onkologie und Hämatologie, Klinikum Oldenburg, Oldenburg, Germany

    Doris Kraemer

  24. Institut für Humangenetik, Medizinische Hochschule Hannover, Hannover, Germany

    Gudrun Göhring

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  1. Peter Paschka
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Correspondence to Peter Paschka.

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Conflict of interest

Bristol Myers Squibb provided dasatinib as study drug and financial support to conduct the trial. The remaining authors declare that they have no onflict of interest.

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Paschka, P., Schlenk, R.F., Weber, D. et al. Adding dasatinib to intensive treatment in core-binding factor acute myeloid leukemia—results of the AMLSG 11-08 trial. Leukemia 32, 1621–1630 (2018). https://doi.org/10.1038/s41375-018-0129-6

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