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Results of a multicenter prospective phase II trial investigating the safety and efficacy of lenalidomide in patients with myelodysplastic syndromes with isolated del(5q) (LE-MON 5)

Leukemia volume 30, pages 1580–1582 (2016)Cite this article

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Herein we report on an open-label, nonrandomized, single-arm, multicenter-, phase II trial conducted by the German MDS-Study-Group, evaluating the safety of lenalidomide in myelodysplastic syndrome (MDS) with isolated del(5q) and trying to identify patterns of disease progression (LE-MON5; EudraCT number: 2008‐001866‐10). The primary endpoint was safety, secondary endpoints were: response defined as transfusion independence on 56 consecutive days after enrollment, International Working Group (IWG) response criteria,1 including cytological and cytogenetic response, time to and duration of transfusion independence, frequency and time to disease progression, incidence and severity of adverse events (AE). In addition, the role of mitochondrial DNA (mtDNA) mutations in the context of treatment with lenalidomide was analyzed.

In order to treat a homogenous patient population we performed a standardized screening procedure including central cytological and histological review of bone marrow and conventional karyotyping. Patients with the need of at least one red cell transfusion within 8 weeks prior to first administration of study drug belonging to the international prognostic scoring system low- or intermediate-1 risk groups with a medullary blast count of <5% and presence of an isolated del(5q) were included. The planned dose of lenalidomide was 10 mg/day, orally on days 1–21 (28-day cycle). Dose adjustment in case of AE was mandatory. The duration of treatment with lenalidomide was limited to 4 months, if there was no response, and was continued only in case of transfusion independence for longer than 4 weeks during the first 4 months of study treatment until reoccurrence of transfusion dependence or progressive disease.

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Acknowledgements

The trial was supported by Celgene, providing the compound, supporting data monitoring and technical processing of bone marrow biopsies. ES wrote the paper, analyzed the data and approved the final version; ArGi performed centralized cytology, contributed essential data and approved the final version; DH performed cytogenetic banding analyses, contributed essential data and approved the final manuscript; GuBu performed centralized histology and approved the final version; UP, FN, KG, RFS, ArGa, FB, ML, AL, PS, UB, NG, GeBu and RH contributed essential data and approved the final version; KS performed cytogenetic banding analyses and approved the final manuscript; MW performed research and approved the final version and UG designed the research, contributed essential data, analyzed the data and approved the final version.

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Authors and Affiliations

  1. Department for Hematology, Oncology and Clinical Immunology, University Hospital, Heinrich-Heine-University, Duesseldorf, Germany

    E Schuler, N Gattermann, M Wulfert, R Haas & U Germing

  2. Department of Hematology, Oncology and Palliative Care, Marien Hospital Duesseldorf, Duesseldorf, Germany

    A Giagounidis

  3. University Medicine Goettingen, Clinics of Hematology and Medical Oncology, Goettingen, Germany

    D Haase, K Shirneshan, F Braulke & U Bacher

  4. Hannover Medical School, Institute of Pathology, Hannover, Germany

    G Büsche

  5. Department of Hematology, University Hospital Dresd,

    U Platzbecker

  6. en, Dresden, Germany

    U Platzbecker

  7. Department of Hematology and Oncology, University Hospital Mannheim, Mannheim, Germany

    F Nolte

  8. Department of Internal Medicine, Technical University of Munich, Munich, Germany

    K Götze

  9. Department of Internal Medicine, University Hospital Ulm, Ulm, Germany

    R F Schlenk

  10. Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany

    A Ganser

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

    A Letsch

  12. University Hospital Freiburg, Internal Medicine, Freiburg, Germany

    M Lübbert

  13. Department of Internal Medicine, University Hospital Frankfurt, Frankfurt, Germany

    G Bug

  14. Department of Oncology, Hematology, BMT with section Pneumology, Hubertus Wald Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    P Schafhausen

Authors
  1. E Schuler
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  2. A Giagounidis
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  7. F Nolte
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  16. U Bacher
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  17. N Gattermann
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  18. M Wulfert
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  19. R Haas
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  20. U Germing
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Corresponding author

Correspondence to U Germing.

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Competing interests

The trial was supported by Celgene, by providing the compound, supporting data monitoring and technical processing of bone marrow biopsies. ES obtained travel grant for attending symposia from Celgene. ArGi obtained personal financial interests from Celgene. DH obtained research support, honorarium and attending symposia from Celgene. UP obtained honoraria and research funding from Celgene. FN obtained honoraria and research funding from Celgene. KG obtained honoraria from Celgene. RFS obtained research support from Celgene. AL obtained research funding from Celgene. KS obtained travel grant for attending symposia from Celgene. GeBu obtained research support, travel grants and honoraria from Celgene. PS obtained financial support for training events from Celgene. NG obtained honoraria and research funding from Celgene. UG obtained speaker honorarium and research support from Celgene. The remaining authors declare no conflicts of interest.

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Schuler, E., Giagounidis, A., Haase, D. et al. Results of a multicenter prospective phase II trial investigating the safety and efficacy of lenalidomide in patients with myelodysplastic syndromes with isolated del(5q) (LE-MON 5). Leukemia 30, 1580–1582 (2016). https://doi.org/10.1038/leu.2015.340

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