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Lymphoma

BRAF inhibitor treatment in classic hairy cell leukemia: a long-term follow-up study of patients treated outside clinical trials

Leukemia volume 34, pages 1454–1457 (2020)Cite this article

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Classic hairy cell leukemia (HCL) is a rare mature B-cell malignancy, which is characterized by pancytopenia accompanied by a susceptibility to infections [1]. Although standard treatment with purine analogues achieves deep and durable remissions in the majority of HCL patients, up to one quarter of patients relapse within 5 years and eventually present with relapsed and/or refractory (r/r) disease [2]. With the discovery of the BRAF V600E mutation as the driving genetic event in HCL, BRAF inhibitors (BRAFi) such as vemurafenib and dabrafenib demonstrated remarkable activity in r/r HCL patients [3,4,5]. There is only limited knowledge how BRAFi should be dosed and scheduled if repetitive long-term treatment is required.

We report 27 retrospectively evaluated HCL patients who were continuously or intermittently treated with vemurafenib and/or dabrafenib at seven different European centers (Heidelberg, n = 10; Caen, n = 9; Munich, n = 3; Innsbruck, n = 2; Basel, n = 1; Erlangen, n = 1; London, n = 1) from 2011 to 2018. Patient characteristics are summarized in supplementary Table S1. Variable BRAFi doses (range, vemurafenib: 240–1920 mg/d per day; dabrafenib: 150–300 mg/d per day) and treatment durations (median 3.8 months, range: 1.7–19.9) were chosen by the treating physicians. This spectrum of individual BRAFi dosing regimens allowed us to investigate whether BRAFi dosing and treatment duration might have influenced time to next treatment (TTT).

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Acknowledgements

We thank Michael Perker (Hämatologisch-onkologische Schwerpunktpraxis, Weilheim, Germany), Thomas Mandel (Klink für Innere Medizin III, SLK-Kliniken Heilbronn, Klinikum am Plattenwald, Bad Friedrichshall, Germany), and Michael Steurer (Department of Internal Medicine V, Division of Hematology & Oncology, Medical University of Innsbruck, Innsbruck, Austria) for collecting data. NL was supported by a HRCMM (Heidelberg Research Center for Molecular Medicine) short-term Career Development Fellowship. TR was supported by a physician scientist fellowship of the Medical Faculty of the University Heidelberg. SD was supported by a grant of the Heidelberg Research Centre for Molecular Medicine (HRCMM) and the BMBF junior group grant by the BMBF within the e:Med initiative. SD and TZ are supported by the Hairy Cell Leukemia Foundation.

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Author notes

  1. These senior authors contributed: Thorsten Zenz, Sascha Dietrich

Authors and Affiliations

  1. Department of Medicine V, Heidelberg University Hospital, Heidelberg, Germany

    Nora Liebers, Tobias Roider, Isabella Haberbosch, Anthony D. Ho, Carsten Müller-Tidow, Peter Dreger & Sascha Dietrich

  2. National Center for Tumor Diseases and German Cancer Research Center, Heidelberg, Germany

    Nora Liebers, Carsten Müller-Tidow & Sascha Dietrich

  3. European Molecular Biology Laboratory (EMBL), Heidelberg, Germany

    Tobias Roider & Sascha Dietrich

  4. Department of Internal Medicine V, Division of Hematology & Oncology, Medical University of Innsbruck, Innsbruck, Austria

    Jan-Paul Bohn & Andreas Pircher

  5. Department of Medicine 5, Universitätsklinikum Erlangen, Erlangen, Germany

    Barbara Ferstl

  6. Department of Hematology and Oncology, St. Claraspital, Basel, Switzerland

    Monika Ebnöther

  7. Department of Hematology, Oncology, Immunology, Palliative Care, Infectious Diseases and Tropical Medicine, Hospital Munich-Schwabing, Munich, Germany

    Clemens-Martin Wendtner

  8. The Royal Marsden Hospital, London, UK

    Claire Dearden

  9. Department of Hematology, Addenbrookes Hospital, Cambridge, UK

    George A. Follows

  10. CHU de Caen, laboratoire d’hématologie, Caen, France

    Xavier Troussard

  11. Division of Medical Oncology and Hematology, Universitätsspital Zürich, Zürich, Switzerland

    Thorsten Zenz

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  1. Nora Liebers
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Correspondence to Sascha Dietrich.

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Liebers, N., Roider, T., Bohn, JP. et al. BRAF inhibitor treatment in classic hairy cell leukemia: a long-term follow-up study of patients treated outside clinical trials. Leukemia 34, 1454–1457 (2020). https://doi.org/10.1038/s41375-019-0646-y

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