Blood Journal
Leading the way in experimental and clinical research in hematology

Administration of bortezomib before and after autologous stem cell transplantation improves outcome in multiple myeloma patients with deletion 17p

  1. Kai Neben1,
  2. Henk M. Lokhorst2,
  3. Anna Jauch3,
  4. Uta Bertsch1,
  5. Thomas Hielscher4,
  6. Bronno van der Holt5,
  7. Hans Salwender6,
  8. Igor W. Blau7,
  9. Katja Weisel8,
  10. Michael Pfreundschuh9,
  11. Christof Scheid10,
  12. Ulrich Dührsen11,
  13. Walter Lindemann12,
  14. Ingo G. H. Schmidt-Wolf13,
  15. Norma Peter14,
  16. Christian Teschendorf15,
  17. Hans Martin16,
  18. Mathias Haenel17,
  19. Hans G. Derigs18,
  20. Marc S. Raab1,
  21. Anthony D. Ho1,
  22. Helgi van de Velde19,
  23. Dirk Hose20,
  24. Pieter Sonneveld21, and
  25. Hartmut Goldschmidt20
  1. 1Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany;
  2. 2Department of Hematology, Utrecht University Medical Center, Utrecht, The Netherlands;
  3. 3Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany;
  4. 4Department of Biostatistics, German Cancer Research Center, Heidelberg, Germany;
  5. 5Hemato Oncology Foundation for Adults in The Netherlands (HOVON) Data Center, Erasmus MC–Daniel den Hoed Cancer Center, Rotterdam, The Netherlands;
  6. 6Department of Internal Medicine II, Asklepios Klinik Altona, Hamburg, Germany;
  7. 7Medical Clinic III Hematology and Oncology, Charité University Medicine Berlin, Berlin, Germany;
  8. 8Department of Hematology, Oncology and Immunology, University of Tübingen, Tübingen, Germany;
  9. 9Department Internal Medicine I, Saarland University Medical School, Homburg/Saar, Germany;
  10. 10Department I of Internal Medicine, University of Cologne, Cologne, Germany;
  11. 11Department of Hematology, University Hospital Essen, Essen, Germany;
  12. 12St Marien Hospital, Katholisches Krankenhaus Hagen, Hagen, Germany;
  13. 13Department of Internal Medicine III, University of Bonn, Bonn, Germany;
  14. 14Department of Internal Medicine II, Carl-Thiem-Klinikum Cottbus, Cottbus, Germany;
  15. 15Department of Internal Medicine, Ruhr-University Bochum, Bochum, Germany;
  16. 16Department of Medicine, Hematology/Oncology, Goethe-University of Frankfurt, Frankfurt, Germany;
  17. 17Department of Internal Medicine III, Klinikum Chemnitz GmbH, Chemnitz, Germany;
  18. 18Department of Internal Medicine III, Klinikum Frankfurt-Hoechst, Frankfurt, Germany;
  19. 19Janssen Research & Development, Beerse, Belgium;
  20. 20Department of Internal Medicine V and National Center for Tumor Diseases, Heidelberg, Germany; and
  21. 21Department of Hematology, Erasmus Medical Center and University, Rotterdam, The Netherlands

Abstract

In patients with multiple myeloma (MM), risk stratification by chromosomal abnormalities may enable a more rational selection of therapeutic approaches. In the present study, we analyzed the prognostic value of 12 chromosomal abnormalities in a series of 354 MM patients treated within the HOVON-65/GMMG-HD4 trial. Because of the 2-arm design of the study, we were able to analyze the effect of a bortezomib-based treatment before and after autologous stem cell transplantation (arm B) compared with standard treatment without bortezomib (arm A). For allanalyzed chromosomal aberrations, progression-free survival (PFS) and overall survival (OS) were at least equal or superior in the bortezomib arm compared with the standard arm. Strikingly, patients with del(17p13) benefited the most from the bortezomib-containing treatment: the median PFS in arm A was 12.0 months and in arm B it was 26.2 months (P = .024); the 3 year-OS for arm A was 17% and for arm B it was 69% (P = .028). After multivariate analysis, del(17p13) was an independent predictor for PFS (P < .0001) and OS (P < .0001) in arm A, whereas no statistically significant effect on PFS (P = .28) or OS (P = .12) was seen in arm B. In conclusion, the adverse impact of del(17p13) on PFS and OS could be significantly reduced by bortezomib-based treatment, suggesting that long-term administration of bortezomib should be recommended for patients carrying del(17p13). This trial is registered at the International Standard Randomised Controlled Trial Number Register as ISRCTN64455289.

  • Submitted September 9, 2011.
  • Accepted December 4, 2011.
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