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Bendamustine compared to fludarabine as second-line treatment in chronic lymphocytic leukemia

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Abstract

Bendamustine demonstrated clinical activity in pre-treated hematological malignancies due to its unique mechanism of action distinct from standard alkylating agents. This study assessed its efficacy in patients with chronic lymphocytic leukemia pre-treated with an alkylator, in comparison to fludarabine. Patients with relapsed chronic lymphocytic leukemia requiring treatment after one previous systemic regimen (usually chlorambucil-based) were randomized to either receive bendamustine 100 mg/m2 on days 1 and 2 of a 4-week cycle or standard fludarabine treatment consisting of 25 mg/m2 on days 1 to 5 every 4 weeks. The primary objective was to achieve non-inferior progression-free survival (PFS) with bendamustine. Out of a total of 96 patients randomized, 92 were eligible, 49 allocated to bendamustine and 43 to fludarabine. About half of the patients received six or more cycles. Overall response rates were 76 % on bendamustine and 62 % on fludarabine, with clinical complete response rates of 27 and 9 %, respectively. Median PFS was 20.1 and 14.8 months (hazard ratio, 0.87; 90 % confidence interval, 0.60–1.27), median overall survival 43.8 and 41.0 months (hazard ratio, 0.82). Thrombocytopenia and gastrointestinal toxicities were marginally more frequent on bendamustine, albeit CTC grade 3/4 event incidence was similar. These data suggest at least comparable efficacy of bendamustine vs. fludarabine, pointing to an alternative treatment option in relapsing CLL patients after chlorambucil containing initial chemotherapy.

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Funding

This work was supported in part by unrestricted research grants from Mundipharma GmbH, Germany, and Ribosepharm GmbH, Germany.

Conflict of interest

Norbert Niederle received honoraria from Mundipharma GmbH; Wolfgang Knauf advised and received honoraria from Mundipharma GmbH; the remaining authors declare no competing financial interests.

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Authors and Affiliations

  1. Medizinische Klinik III, Klinikum Leverkusen gGmbH, Am Gesundheitspark 11, D-51375, Leverkusen, Germany

    Norbert Niederle & Dirk Megdenberg

  2. Medizinische Klinik I, Ev. Krankenhaus Hamm, Germany

    Leopold Balleisen

  3. Hämatologicum, Essen, Germany

    Wolfgang Heit

  4. Onkologische Gemeinschaftspraxis, Frankfurt, Germany

    Wolfgang Knauf

  5. Praxis für Hämatologie und internistische Onkologie, Weiden, Germany

    Johann Weiß

  6. Onkologische Schwerpunktpraxis, Hildesheim, Germany

    Werner Freier

  7. WiSP Research Institute, Langenfeld, Germany

    Axel Hinke & Stefan Ibach

  8. Onkologische Schwerpunktpraxis, Olpe, Germany

    Hartmut Eimermacher

Authors
  1. Norbert Niederle
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  2. Dirk Megdenberg
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  3. Leopold Balleisen
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  4. Wolfgang Heit
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  5. Wolfgang Knauf
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  6. Johann Weiß
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  7. Werner Freier
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  8. Axel Hinke
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  9. Stefan Ibach
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  10. Hartmut Eimermacher
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Corresponding author

Correspondence to Norbert Niederle.

Additional information

Presented in abstract form at the 15th Congress of the European CanCer Organisation and 34th Congress of the European Society for Medical Oncology, Berlin, Germany, September 20–24, 2009.

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Niederle, N., Megdenberg, D., Balleisen, L. et al. Bendamustine compared to fludarabine as second-line treatment in chronic lymphocytic leukemia. Ann Hematol 92, 653–660 (2013). https://doi.org/10.1007/s00277-012-1660-6

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  • DOI: https://doi.org/10.1007/s00277-012-1660-6

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