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

Author:

Neben Kai1,Lokhorst Henk M.2,Jauch Anna3,Bertsch Uta1,Hielscher Thomas4,van der Holt Bronno5,Salwender Hans6,Blau Igor W.7,Weisel Katja8,Pfreundschuh Michael9,Scheid Christof10,Dührsen Ulrich11,Lindemann Walter12,Schmidt-Wolf Ingo G. H.13,Peter Norma14,Teschendorf Christian15,Martin Hans16,Haenel Mathias17,Derigs Hans G.18,Raab Marc S.1,Ho Anthony D.1,van de Velde Helgi19,Hose Dirk20,Sonneveld Pieter21,Goldschmidt Hartmut20

Affiliation:

1. Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany;

2. Department of Hematology, Utrecht University Medical Center, Utrecht, The Netherlands;

3. Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany;

4. Department of Biostatistics, German Cancer Research Center, Heidelberg, Germany;

5. Hemato Oncology Foundation for Adults in The Netherlands (HOVON) Data Center, Erasmus MC–Daniel den Hoed Cancer Center, Rotterdam, The Netherlands;

6. Department of Internal Medicine II, Asklepios Klinik Altona, Hamburg, Germany;

7. Medical Clinic III Hematology and Oncology, Charité University Medicine Berlin, Berlin, Germany;

8. Department of Hematology, Oncology and Immunology, University of Tübingen, Tübingen, Germany;

9. Department Internal Medicine I, Saarland University Medical School, Homburg/Saar, Germany;

10. Department I of Internal Medicine, University of Cologne, Cologne, Germany;

11. Department of Hematology, University Hospital Essen, Essen, Germany;

12. St Marien Hospital, Katholisches Krankenhaus Hagen, Hagen, Germany;

13. Department of Internal Medicine III, University of Bonn, Bonn, Germany;

14. Department of Internal Medicine II, Carl-Thiem-Klinikum Cottbus, Cottbus, Germany;

15. Department of Internal Medicine, Ruhr-University Bochum, Bochum, Germany;

16. Department of Medicine, Hematology/Oncology, Goethe-University of Frankfurt, Frankfurt, Germany;

17. Department of Internal Medicine III, Klinikum Chemnitz GmbH, Chemnitz, Germany;

18. Department of Internal Medicine III, Klinikum Frankfurt-Hoechst, Frankfurt, Germany;

19. Janssen Research & Development, Beerse, Belgium;

20. Department of Internal Medicine V and National Center for Tumor Diseases, Heidelberg, Germany; and

21. Department of Hematology, Erasmus Medical Center and University, Rotterdam, The Netherlands

Abstract

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.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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