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Response-adapted consolidation with bortezomib after ASCT improves progression-free survival in newly diagnosed multiple myeloma

Leukemia volume 31, pages 1463–1466 (2017)Cite this article

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Frontline induction chemotherapy followed by high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) remains the standard treatment for newly diagnosed multiple myeloma (NDMM) in transplant-eligible patients.1 However, progression-free survival (PFS) does often not exceed 2–3 years.1 Thus, consolidation therapy designed to deepen and prolong responses to extend progression-free intervals is increasingly being explored.2, 3, 4 We present a pre-specified single dataset analysis on the combined data of two randomized, controlled, open-label phase III studies of bortezomib consolidation. The objective of both similarly designed studies was to evaluate the efficacy of bortezomib consolidation after ASCT in NDMM patients aged (i) ⩽60 years, of whom 71% had received a bortezomib-based induction regimen (VCD/VD; study MMY3012; DSMM XIb; NCT00416273) and (ii) 61–75 years, of whom 79% had received an induction regimen without bortezomib (high-dose dexamethasone, VAD, AD or idarubicin/dexamethasone; physician’s choice; study MMY3013; DSMM X; NCT00416208). No patient received immunomodulatory agents, and no patient received more than one line of induction. More than half (54%) of patients received 3 cycles of induction therapy; 19% received 4 cycles; these were balanced between arms. Pretreatment and SCT had to be completed 60–120 days prior to enrollment. All patients had to be free of progression and were excluded if they had non-secretory MM or peripheral neuropathy CTCAE grade⩾2. The planned period of treatment/observation was 25 weeks, after which patients were followed for a minimum of 30 months.

The studies were conducted at 47 departments in Germany (see Supplementary Information) from October 2006 until May 2013, according to the Declaration of Helsinki, Good Clinical Practice guidelines and applicable regulatory requirements. Independent ethics committees approved the protocols and all amendments. All patients provided written informed consent.

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Acknowledgements

We thank the patients who participated in these trials and their families, as well as the investigators and staff at all MMY-3012/3013 clinical sites in Germany, as part of the German Multiple Myeloma Study Group (DSMM). We also like to acknowledge the writing support of Megan Barrett of FireKite, an Ashfield company, part of UDG Healthcare plc, and Mark Richardson, who provided medical writing support on behalf of FireKite, during the development of this manuscript, which was funded by Millennium Pharmaceuticals Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited and Janssen-Cilag GmbH. ClinicalTrials.gov IDs: NCT00416273, NCT00416208. This research was supported by Janssen-Cilag GmbH.

Author contributions

Conception and design: HE, CS, MV. Collection and assembly of the data: All authors. The data analysis and interpretation: HE, CS, MV, JM, PL. Letter writing: All authors. Final approval of the letter: All authors. All authors had full access to the study data and were involved in the decision to submit for publication.

Author information

Authors and Affiliations

  1. Medizinische Klinik und Poliklinik II, Julius Maximilians Universität Würzburg, Würzburg, Germany

    H Einsele & S Knop

  2. Janssen-Cilag GmbH, Neuss, Germany

    M Vogel

  3. Acromion GmbH, Frechen, Germany

    J Müller

  4. Universitätsklinikum Münster, Münster, Germany

    M Kropff

  5. Klinikum Oldenburg Klinik für Onkologie und Hämatologie, Oldenburg, Germany

    B Metzner

  6. Zentrum für Innere Medizin Universitätsklinikum Ulm, Ulm, Germany

    C Langer & P Liebisch

  7. University Hospital Jena, Jena, Germany

    H Sayer

  8. Onkologie Universitätsmedizin Göttingen, Göttingen, Germany

    W Jung

  9. St Marien Hospital Hamm Knappenstraße, Hamm, Germany

    H A Dürk

  10. Asklepios Klinik Altona, Hamburg, Germany

    H Salwender

  11. Medizinische Klinik 5—Hämatologie und Onkologie, Nürnberg, Germany

    H Wandt

  12. Technische Universität München Medizinische Klinik, München, Germany

    F Bassermann

  13. Universitätsklinikum Schleswig-Holstein, Kiel, Germany

    M Gramatzki

  14. Universitätsklinkum Erlangen, Erlangen, Germany

    W Rösler

  15. University Hospital Halle, Halle (Saale), Germany

    H-H Wolf

  16. Schwarzwald-Baar Klinikum, Villingen-Schwenningen, Germany

    W Brugger

  17. University of Freiburg, Freiburg, Germany

    M Engelhardt

  18. Otto-von-Guericke University, Magdeburg, Germany

    T Fischer

  19. Schön Klinik Starnberger See, Berg, Germany

    C Straka

Authors
  1. H Einsele
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  2. S Knop
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  3. M Vogel
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  4. J Müller
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  5. M Kropff
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  9. W Jung
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  10. H A Dürk
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  11. H Salwender
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  13. F Bassermann
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  16. H-H Wolf
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  18. M Engelhardt
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  20. P Liebisch
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  21. C Straka
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Corresponding author

Correspondence to H Einsele.

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Competing interests

The authors declare the following: HE: honoraria (Celgene, Janssen); consulting/advisory role (Celgene, Janssen, Novartis, Amgen); Speakers’ bureau (Celgene, Janssen, Novartis, Amgen); research funding (Celgene, Janssen); travel/accommodation/expenses (Celgene, Janssen, Novartis). MV: employment (Janssen-Cilag GmbH). SK: honoraria (Celgene, Janssen); consulting/advisory role (Celgene, Novartis, Onyx). MK: consulting/advisory role (Celgene, Janssen, Onyx); Speakers’ bureau (Celgene, Janssen, Onyx); travel/accommodation/expenses (Celgene, Janssen). BM: consulting/advisory role (Amgen, Sanofi); travel/accommodation/expenses (Celgene, Takeda). H Sayer: consulting/advisory role (Riemser Pharma). H Salwender: honoraria (Janssen); travel/accommodation/expenses (Janssen). FB: travel/accommodation/expenses (Celgene). MG: research funding (Janssen); travel/accommodation/expenses (Janssen). WR: consulting/advisory role (Janssen); travel/accommodation/expenses (Janssen). ME: honoraria (Celgene, Janssen, MSD); consulting/advisory role (Celgene, Janssen, MSD); research funding (Celgene); travel/accommodation/expenses (Celgene). TF: honoraria (Novartis); consulting/advisory role (Novartis). CS: honoraria (Celgene, Janssen, Onyx); consulting/advisory role (Celgene, Janssen, Onyx); research funding (Celgene, Chugai); expert testimony (Celgene, Onyx); travel/accommodation/expenses (Celgene, Onyx). The remaining authors declare no conflict of interest.

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Einsele, H., Knop, S., Vogel, M. et al. Response-adapted consolidation with bortezomib after ASCT improves progression-free survival in newly diagnosed multiple myeloma. Leukemia 31, 1463–1466 (2017). https://doi.org/10.1038/leu.2017.83

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