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Chronic myeloproliferative neoplasms

Pomalidomide in myeloproliferative neoplasm-associated myelofibrosis

Leukemia volume 31, pages 889–895 (2017)Cite this article

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Abstract

Myeloproliferative neoplasm (MPN)-associated myelofibrosis is a MPN characterized by bone marrow fibrosis, cytopenias, splenomegaly and constitutional symptoms. Pomalidomide, an immune-modifying drug, is reported to improve anaemia and thrombocytopenia in some patients with MPN-associated myelofibrosis. We designed a phase 2 study of pomalidomide in patients with MPN-associated myelofibrosis and anaemia and/or thrombocytopenia and/or neutropenia. Subjects received pomalidomide 2.0 mg/day in cohort 1 (n=38) or 0.5 mg/day in cohort 2 (n=58). Prednisolone was added if there was no response after 3 months in cohort 1 and based on up-front randomization in cohort 2 if there was no response at 3 or 6 months. Response rates were 39% (95% confidence interval (CI), 26–55%) in cohort 1 and 24% (95% CI, 15–37%) in cohort 2. In a multivariable logistic regression model pomalidomide at 2.0 mg/day (odds ratio (OR), 2.62; 95% CI, 1.00–6.87; P=0.05) and mutated TET2 (OR, 5.07; 95% CI, 1.16–22.17; P=0.03) were significantly associated with responses. Median duration of responses was 13.0 months (range 0.9–52.7). There was no significant difference in response rates or duration in subjects receiving or not receiving prednisolone. Clinical trial MPNSG 01-09 is registered at ClinicalTrials.gov (NCT00949364) and clinicaltrialsregister.eu (EudraCT Number: 2009-010738-23)

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Acknowledgements

This work was supported by an unrestricted grant from Celgene and a research grant funded by the Else-Kröner Fresenius Stiftung (project number 2011_A107). We thank Cora Heiligensetzer, Silja Mack, Ulrike Sutter and Regina Reim for their continuous support.

Author contributions

Conception and design: RFS, AR, MG and KD; provision of study materials or patients: RFS, FS, AR, EJ, NG, HH, CW, AH, UP, PS, IWB, WV, FHH, MW, HK, VT, AB, HD, MG and KD; collection and assembly of data: RFS and FS; data analysis and interpretation: RFS and FS; manuscript writing: RFS and FS; final approval of manuscript: RFS, FS, AR, EJ, NG, HH, CW, AH, UP, PS, IWB, WV, FHH, MW, HK, VT, AB, HD, MG and KD.

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Author notes

  1. F H Heidel

    Present address: 19Current address: Internal Medicine II, Jena University Hospital, Jena, Germany.,

  2. R F Schlenk and F Stegelmann: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany

    R F Schlenk, F Stegelmann, V Teleanu, H Döhner & K Döhner

  2. NCT Trial Center, National Center for Tumor Diseases (NCT), Heidelberg, Germany

    R F Schlenk

  3. Hematology and Oncology, University Hospital Mannheim, Mannheim, Germany

    A Reiter

  4. Department of Internal Medicine IV, University Hospital Aachen, Aachen, Germany

    E Jost

  5. Department of Hematology, Oncology and Clinical Immunology, University Hospital Düsseldorf, Düsseldorf, Germany

    N Gattermann

  6. Department of Hematology and Oncology, Stauferklinikum Mutlangen, Mutlangen, Germany

    H Hebart

  7. Department of Internal Medicine I, University Hospital and Faculty of Medicine, University of Freiburg, Freiburg, Germany

    C Waller

  8. Internal Medicine II, Jena University Hospital, Jena, Germany

    A Hochhaus

  9. Department of Internal Medicine I, University Hospital Dresden and GP Hematology and Oncology, Dresden, Germany

    U Platzbecker

  10. Department of Internal Medicine II, University Hospital Hamburg, Hamburg, Germany

    P Schafhausen

  11. Department of Hematology and Oncology, Charité, Campus Benjamin Franklin, Berlin, Germany

    I W Blau

  12. Center of Outpatient Hematology and Oncology, Bonn, Germany

    W Verbeek

  13. Department of Hematology and Oncology, University Hospital Magdeburg, Magdeburg, Germany

    F H Heidel

  14. Department of Pathology, University of Freiburg, Freiburg, Germany

    M Werner

  15. Department of Pathology, Hannover Medical School, Hannover, Germany

    H Kreipe

  16. Division of Biostatistics, German Cancer Research Center, Heidelberg, Germany

    A Benner

  17. Department of Oncology, Klinikum Minden, Minden, Germany

    M Grießhammer

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  1. R F Schlenk
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Corresponding author

Correspondence to R F Schlenk.

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Authors’ disclosures of potential conflict of interest. Research funding by Celgene.

Additional information

Presented in part at the 55th Annual Meeting of the American Society of Hematology, 2013.

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Schlenk, R., Stegelmann, F., Reiter, A. et al. Pomalidomide in myeloproliferative neoplasm-associated myelofibrosis. Leukemia 31, 889–895 (2017). https://doi.org/10.1038/leu.2016.299

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