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Chronic myelogenous leukemia

Safety and efficacy of the combination of pegylated interferon-α2b and dasatinib in newly diagnosed chronic-phase chronic myeloid leukemia patients

Leukemia volume 30, pages 1853–1860 (2016)Cite this article

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Abstract

Dasatinib (DAS) and interferon-α have antileukemic and immunostimulatory effects and induce deep responses in chronic myeloid leukemia (CML). We assigned 40 newly diagnosed chronic-phase CML patients to receive DAS 100 mg o.d. followed by addition of pegylated interferon-α2b (PegIFN) after 3 months (M3). The starting dose of PegIFN was 15 μg/week and it increased to 25 μg/week at M6 until M15. The combination was well tolerated with manageable toxicity. Of the patients, 84% remained on PegIFN at M12 and 91% (DAS) and 73% (PegIFN) of assigned dose was given. Only one patient had a pleural effusion during first year, and three more during the second year. After introduction of PegIFN we observed a steep increase in response rates. Major molecular response was achieved in 10%, 57%, 84% and 89% of patients at M3, M6, M12 and M18, respectively. At M12, MR4 was achieved by 46% and MR4.5 by 27% of patients. No patients progressed to advanced phase. In conclusion, the combination treatment appeared safe with very promising efficacy. A randomized comparison of DAS±PegIFN is warranted.

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Acknowledgements

We thank Berit Bjelkåsen, Ann Jorunn Sandstå and Sven M Carlsen at the Dept of Applied Clinical Research (AKF), NTNU for WebCRF and other assistance during this study. We thank patients and all study personnel for their efforts. The Norwegian University of Science and Technology (NTNU, Trondheim, Norway) sponsored the study on behalf of the Nordic CML Study Group (NCMLSG). The trial was supported by a grant from Bristol-Myers Squibb to NTNU. Neither sponsor nor BMS had any role in study design, collection, analysis or interpretation of data or preparation of this report.

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Author notes

  1. S Mustjoki and U Olsson-Strömberg: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Hematology, St Olavs Hospital, Trondheim, Norway

    H Hjorth-Hansen

  2. Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway

    H Hjorth-Hansen

  3. Department of Hematology, Aarhus University Hospital, Aarhus, Denmark

    J Stentoft

  4. Department of Hematology and Vascular Disorders, Skåne University Hospital, Lund, Sweden

    J Richter

  5. University of Helsinki and Department of Hematology, Hematology Research Unit Helsinki, Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland

    P Koskenvesa, K Porkka, A Lübking & S Mustjoki

  6. Department of Hematology, Uppsala University Hospital, Uppsala, Sweden

    M Höglund & U Olsson-Strömberg

  7. Department of Medical and Health Sciences, Department of Hematology, Linköping University, County Council of Östergötland, Linköping, Sweden

    A Dreimane

  8. Department of Hematology, Oslo University Hospital, Rikshospitalet, Oslo, Norway

    T Gedde-Dahl

  9. Department of Internal Medicine, Haukeland University Hospital and Department of Clinical Science, Hematology Section, University of Bergen, Bergen, Norway

    B T Gjertsen

  10. Department of Hematology, University Hospital of North Norway, Tromsø, Norway

    F X Gruber

  11. Department of Hematology, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden

    L Stenke

  12. Department of Internal Medicine, Sunderbysjukhuset, Luleå, Sweden

    K M Eriksson

  13. Department of Hematology, Umeå University Hospital, Umeå, Sweden

    B Markevärn

  14. Department of Hematology, Odense University Hospital, Odense, Denmark

    H Vestergaard

  15. Department of Hematology, Roskilde Hospital, Roskilde, Denmark

    L Udby

  16. Department of Hematology, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark

    O W Bjerrum

  17. Department of Statistics, Uppsala University, Uppsala, Sweden

    I Persson

  18. Department of Clinical Chemistry, University of Helsinki, Helsinki, Finland

    S Mustjoki

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Competing interests

The Nordic CML Study group is an open academic forum for research on CML, and has performed clinical studies and received financing for this in collaborations with BMS, Novartis, Pfizer and MSD. The present study was supported by MSD and BMS by provision of study drug free of charge and BMS gave financial support for study administration. Individual investigators have the following ties to declare: Henrik Hjorth-Hansen: ARIAD and BMS (consulting); Jesper Stentoft: Novartis, BMS, Pfizer, ARIAD (study support); Johan Richter: ARIAD, BMS and Novartis (consulting); Perttu Koskenvesa: ARIAD (consulting); Martin Höglund: Akinion Oharmaceuticals (consulting) and Janssen-Cilag (temporary advisory board); Kimmo Porkka: Novartis, BMS and Pfizer honoraria (advisory board or speaker) and research funding; Bjørn Tore Gjertsen: ARIAD, Bayer, BerGenBio, Pfizer, MedImmune, Novartis and Roche (consulting and advisory boards). Stock equity owner: KinN Therapeutics and ACT2, Ole Weis Bjerrum: BMS, Novartis, Ariad and Pfizer; Satu Mustjoki: Novartis, BMS and Pfizer honoraria (advisory board or speaker) and Ariad research funding; Ulla Olsson-Strömberg: ARIAD (honoraria). The other authors declare no conflict of interest.

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Hjorth-Hansen, H., Stentoft, J., Richter, J. et al. Safety and efficacy of the combination of pegylated interferon-α2b and dasatinib in newly diagnosed chronic-phase chronic myeloid leukemia patients. Leukemia 30, 1853–1860 (2016). https://doi.org/10.1038/leu.2016.121

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