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Prevalence, clonal dynamics and clinical impact of TP53 mutations in patients with myelodysplastic syndrome with isolated deletion (5q) treated with lenalidomide: results from a prospective multicenter study of the german MDS study group (GMDS)

Leukemia volume 30, pages 1956–1959 (2016)Cite this article

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Mutations of TP53 have been detected in variable frequencies in myelodysplastic syndromes (MDS) with a higher prevalence in advanced stages. They have been recognized as adverse prognostic markers in MDS and acute myeloid leukemia (AML) with regard to overall survival and time to progression.1, 2, 3, 4 A recent retrospective analysis of untreated patients with MDS and isolated deletion (5q) (MDS del(5q)) has found a cumulative progression rate of 18% after 5 years,5 suggesting that MDS del(5q) is more heterogeneous than initially suspected. However, all studies evaluating the prognostic relevance of TP53 mutations in patients with MDS del(5q) were performed retrospectively and revealed contradictory results.3, 4 Lenalidomide (Len) leads to transfusion independency (TI) in ~60–70% of patients with MDS del(5q).6, 7, 8 In contrast to initial concerns that Len might promote leukemic transformation, Kuendgen et al.9 find an increased progression rate in transfusion dependent patients treated with Len.

To add for the first time prospective evaluated data on the role of mutations of TP53 in MDS del(5q) we report on the results of a prospective German open label, multicenter trial evaluating the safety and efficacy of Len in patients with MDS del(5q) and the prevalence and clinical impact of TP53 mutations in this particular patient cohort. The clinical data of this trial have recently been published. For further information on study design and response criteria, the reader is referred to the publication by Schuler et al.10

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Acknowledgements

We thank Christiane Schumann for critically reviewing the manuscript. The trial was supported by Celgene, by providing the compound, supporting data monitoring and technical processing of bone marrow biopsies. Roche Diagnostics GmbH (Penzberg, Germany) provided training courses within the context of the IRON-II study.

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Authors and Affiliations

  1. III. Medizinische Klinik, Hämatologie und Onkologie, Universitätsmedizin Mannheim, Mannheim, Germany

    M Mossner, J-C Jann, D Nowak, V Nowak, J Pressler, J Obländer, S Fey, N Müller, E Lauinger-Lörsch, G Metzgeroth, W-K Hofmann & F Nolte

  2. Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus, Dresden, Germany

    U Platzbecker

  3. Klinik für Hämatologie, Onkologie und Palliativmedizin, Marienhospital, Düsseldorf, Germany

    A Giagounidis

  4. III. Medizinischen Klinik des Klinikums rechts der Isar der Technischen Universität München, München, Germany

    K Götze

  5. Medizinische Klinik für Hämatologie, Onkologie, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Berlin, Germany

    A Letsch

  6. Abteilung für Hämatologie und Onkologie, Universitätsmedizin Göttingen, Göttingen, Germany

    D Haase, K Shirneshan & F Braulke

  7. Klinik für Innere Medizin III, Zentrum für Innere Medizin, Universitätsklinikum Ulm, Ulm, Germany

    R F Schlenk

  8. MLL Münchner Leukämielabor GmbH, München, Germany

    T Haferlach

  9. II. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany

    P Schafhausen

  10. Abteilung für Hämatologie/Onkologie, Medizinische Klinik II, Klinikum der J.W. Goethe-Universität Frankfurt, Frankfurt, Germany

    G Bug

  11. Abteilung für Innere Medizin I, Hämatologie und Onkologie, Universitätsklinikum Freiburg, Freiburg, Germany

    M Lübbert

  12. Abteilung für Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation, Medizinische Hochschule Hannover, Hannover, Germany

    A Ganser

  13. Institut für Pathologie, Zentrum für Pathologie, Forensik und Genetik, Medizinische Hochschule Hannover, Hannover, Germany

    G Büsche

  14. Abteilung für Medizinische Statistik, Biomathematik und Informationsverarbeitung, Medizinische Fakultät Mannheim der Universität Heidelberg, Heidelberg, Germany

    C Weiß

  15. Abteilung für Hämatologie, Onkologie und klinische Immunologie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany

    E Schuler & U Germing

Authors
  1. M Mossner
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  2. J-C Jann
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  17. G Büsche
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  18. E Schuler
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  28. U Germing
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  29. F Nolte
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Corresponding author

Correspondence to F Nolte.

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Competing interests

FN: speaker honoraria, research founding and travel grants from Celgene. DN, DH, WKH and UG: speaker honoraria and research support from Celgene. AGi: personal financial interest. KG, FB, TH: speaker honoraria from Celgene. RFS: research support from Celgene. PS: educational grants from Celgene. GBu: speaker honoraria, research support and travel grants from Celgene. ES: travel grants from Celgene. The remaining authors have no conflict of interest.

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Mossner, M., Jann, JC., Nowak, D. et al. Prevalence, clonal dynamics and clinical impact of TP53 mutations in patients with myelodysplastic syndrome with isolated deletion (5q) treated with lenalidomide: results from a prospective multicenter study of the german MDS study group (GMDS). Leukemia 30, 1956–1959 (2016). https://doi.org/10.1038/leu.2016.111

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