Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Myeloma

Cyclophosphamide, bortezomib and dexamethasone induction for newly diagnosed multiple myeloma: high response rates in a phase II clinical trial

Leukemia volume 23, pages 1337–1341 (2009)Cite this article

Abstract

We have studied a three-drug combination with cyclophosphamide, bortezomib and dexamethasone (CyBorD) on a 28-day cycle in the treatment of newly diagnosed multiple myeloma (MM) patients to assess response and toxicity. The primary endpoint of response was evaluated after four cycles. Thirty-three newly diagnosed, symptomatic patients with MM received bortezomib 1.3 mg/m2 intravenously on days 1, 4, 8 and 11, cyclophosphamide 300 mg/m2 orally on days 1, 8, 15 and 22 and dexamethasone 40 mg orally on days 1–4, 9–12 and 17–20 on a 28-day cycle for four cycles. Responses were rapid with a mean 80% decline in the sentinel monoclonal protein at the end of two cycles. The overall intent to treat response rate (⩾ partial response) was 88%, with 61% of very good partial response or better (⩾VGPR) and 39% of complete/near complete response (CR/nCR). For the 28 patients who completed all four cycles of therapy, the CR/nCR rate was 46% and VGPR rate was 71%. All patients undergoing stem cell harvest had a successful collection. Twenty-three patients underwent stem cell transplantation (SCT) and are evaluable through day 100 with CR/nCR documented in 70% and ⩾VGPR in 74%. In conclusion, CyBorD produces a rapid and profound response in patients with newly diagnosed MM with manageable toxicity.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Kumar SK, Rajkumar SV, Dispenzieri A, Lacy M, Hayman S, Buadi F et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood 2008; 111: 2516–2520.

    Article  CAS  Google Scholar 

  2. Barlogie B, Tricot GJ, van Rhee F, Angtuaco E, Walker R, Epstein J et al. Long-term outcome results of the first tandem autotransplant trial for multiple myeloma. Br J Haematol 2006; 135: 158–164.

    Article  Google Scholar 

  3. Brenner H, Gondos A, Pulte D . Recent major improvement in long-term survival of younger patients with multiple myeloma. Blood 2008; 111: 2521–2526.

    Article  CAS  Google Scholar 

  4. Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer E, Facon T et al. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med 2005; 352: 2487–2498.

    Article  CAS  Google Scholar 

  5. Weber D . Thalidomide and its derivatives: new promise for multiple myeloma. Cancer Control 2003; 10: 375–383.

    Article  Google Scholar 

  6. Singhal S, Mehta J, Desikan R, Ayers D, Roberson P, Eddlemon P et al. Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med 1999; 341: 1565–1571.

    Article  CAS  Google Scholar 

  7. Rajkumar SV, Hayman SR, Lacy MQ, Dispenzieri A, Geyer S, Kabat B et al. Combination therapy with lenalidomide plus dexamethasone (REV/DEX) for newly diagnosed myeloma. Blood 2005; 106: 4050–4053.

    Article  CAS  Google Scholar 

  8. Rajkumar SV, Blood E, Vesole D, Fonseca R, Greipp PR . Phase III clinical trial of thalidomide plus dexamethasone compared with dexamethasone alone in newly diagnosed multiple myeloma: a clinical trial coordinated by the Eastern Cooperative Oncology Group. J Clin Oncol 2006; 24: 431–436.

    Article  CAS  Google Scholar 

  9. San Miguel JF, Schlag R, Khuageva NK, Dimopoulos M, Shpilberg O, Kropff M et al. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med 2008; 359: 906–917.

    Article  CAS  Google Scholar 

  10. Palumbo A, Bringhen S, Caravita T, Merla E, Capparella V, Callea V et al. Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: randomized controlled trial. Lancet 2006; 367: 825–831.

    Article  CAS  Google Scholar 

  11. Wang M, Weber DM, Delasalle K, Alexanian R . Thalidomide–dexamethasone as primary therapy for advanced multiple myeloma. Am J Hematol 2005; 79: 194–197.

    Article  CAS  Google Scholar 

  12. Barlogie B, Pineda-Roman M, van Rhee F, Haessler J, Anaissie E, Hollmig K et al. Thalidomide arm of total therapy 2 improves complete remission duration and survival in myeloma patients with metaphase cytogenetic abnormalities. Blood 2008; 112: 3115–3121.

    Article  CAS  Google Scholar 

  13. Lacy MQ, Gertz MA, Dispenzieri A, Hayman S, Geyer S, Kabat B et al. Long-term results of response to therapy, time to progression, and survival with lenalidomide plus dexamethasone in newly diagnosed myeloma. Mayo Clin Proc 2007; 82: 1179–1184.

    Article  CAS  Google Scholar 

  14. Jagannath S, Durie BG, Wolf J, Camacho E, Irwin D, Lutzky J et al. Bortezomib therapy alone and in combination with dexamethasone for previously untreated symptomatic multiple myeloma. Br J Haematol 2005; 129: 776–783.

    Article  CAS  Google Scholar 

  15. Richardson PG, Hideshima T, Anderson KC . Bortezomib (PS-341): a novel, first-in-class proteasome inhibitor for the treatment of multiple myeloma and other cancers. Cancer Control 2003; 10: 361–369.

    Article  Google Scholar 

  16. Wang M, Giralt S, Delasalle K, Handy B, Alexanian R . Bortezomib in combination with thalidomide–dexamethasone for previously untreated multiple myeloma. Hematology 2007; 12: 235–239.

    Article  CAS  Google Scholar 

  17. Barlogie B, Anaissie E, van Rhee F, Haessler J, Hollmig K, Pineda-Roman M et al. Incorporating bortezomib into upfront treatment for multiple myeloma: early results of total therapy 3. Br J Haematol 2007; 138: 176–185.

    Article  CAS  Google Scholar 

  18. Trieu Y, Trudel S, Pond GR, Mikhael J, Jaksic W, Reece D et al. Weekly cyclophosphamide and alternate-day prednisone: an effective, convenient, and well-tolerated oral treatment for relapsed multiple myeloma after autologous stem cell transplantation. Mayo Clin Proc 2005; 80: 1578–1582.

    Article  CAS  Google Scholar 

  19. Reece DE, Piza Rodriguez G, Chen C, Trudel S, Kukreti V, Mikhael J et al. Phase I-II trial of bortezomib plus oral cyclophosphamide and prednisone in relapsed and refractory multiple myeloma. J Clin Oncol 2008; 26: 4777–4783.

    Article  CAS  Google Scholar 

  20. Blade J, Sampson D, Reece D, Apperley J, BJOrkstrand B, Gahrton G et al. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haematopoietic stem cell transplantation. Br J Haematol 1998; 102: 1115–1123.

    Article  CAS  Google Scholar 

  21. Durie BG, Harousseau JL, Miguel JS, Blade J, Barlogie B, Anderson K et al. International uniform response criteria for multiple myeloma. Leukemia 2006; 20: 1467–1473.

    Article  CAS  Google Scholar 

  22. Rajkumar SV, Durie BG . Eliminating the complete response penalty from myeloma response criteria. Blood 2008; 111: 5759–5760.

    Article  CAS  Google Scholar 

  23. Greipp PR, San Miguel J, Durie BG, Crowley J, Barlogie B, Blade J et al. International staging system for multiple myeloma. J Clin Oncol 2005; 23: 3412–3420.

    Article  Google Scholar 

  24. Prince HM, Imrie K, Sutherland DR, Keating A, Meharchand J, Crump RM et al. Peripheral blood progenitor cell collections in multiple myeloma: predictors and management of inadequate collections. Br J Haematol 1996; 93: 142–145.

    Article  CAS  Google Scholar 

  25. Gertz MA, Lacy MQ, Inwards DJ, Pineda A, Chen M, Gastineau D et al. Factors influencing platelet recovery after blood cell transplantation in multiple myeloma. Bone Marrow Transplant 1997; 20: 375–380.

    Article  CAS  Google Scholar 

  26. Kumar S, Dispenzieri A, Lacy MQ, Hayman S, Buadi F, Gastineau D et al. Impact of lenalidomide therapy on stem cell mobilization and engraftment post-peripheral blood stem cell transplantation in patients with newly diagnosed myeloma. Leukemia 2007; 21: 2035–2042.

    Article  CAS  Google Scholar 

  27. Paripati H, Stewart AK, Cabou S, Dueck A, Zepeda V, Pirooz N et al. Compromised stem cell mobilization following induction therapy with lenalidomide in myeloma. Leukemia 2008; 22: 1282–1284.

    Article  CAS  Google Scholar 

  28. Attal M, Harousseau JL . Standard therapy versus autologous transplantation in multiple myeloma. Hematol Oncol Clin North Am 1997; 11: 133–146.

    Article  CAS  Google Scholar 

  29. Child JA, Morgan GJ, Davies FE, Owen R, Bell S, Hawkins K et al. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med 2003; 348: 1875–1883.

    Article  CAS  Google Scholar 

  30. Attal M, Harousseau JL, Facon T, Guilhot F, Doyen F, Fuzibet J-G et al. Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med 2003; 349: 2495–2502.

    Article  CAS  Google Scholar 

  31. Attal M, Harousseau JL, Leyvraz S, Doyen C, Hulin C, Benboubker L et al. Maintenance therapy with thalidomide improves survival in patients with multiple myeloma. Blood 2006; 108: 3289–3294.

    Article  CAS  Google Scholar 

  32. Cavo M, Tosi P, Zamagni E, Cellini C, Tacchetti P, Patriarca F et al. Prospective, randomized study of single compared with double autologous stem-cell transplantation for multiple myeloma: Bologna 96 clinical study. J Clin Oncol 2007; 25: 2434–2441.

    Article  Google Scholar 

  33. Palumbo A, Bringhen S, Liberati AM, Caravita T, Falcone A, Callea V et al. Oral melphalan, prednisone, and thalidomide in elderly patients with multiple myeloma: updated results of a randomized, controlled trial. Blood 2008; 112: 3107–3114.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This investigator-initiated trial was supported by a grant from Millennium Pharmaceuticals.

Author information

Authors and Affiliations

  1. Division of Hematology/Oncology, Mayo Clinic, Scottsdale, AZ, USA

    C B Reeder, J Hentz, B Noble, N A Pirooz, J E Spong, V H J Zepeda, J R Mikhael, J F Leis, P L Bergsagel, R Fonseca & A K Stewart

  2. Division of Hematology/Oncology, Princess Margaret Hospital, Toronto, Ontario, Canada

    D E Reece, V Kukreti, C Chen, S Trudel & J G Piza

Authors
  1. C B Reeder
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D E Reece
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. V Kukreti
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S Trudel
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J Hentz
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. B Noble
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. N A Pirooz
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. J E Spong
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. J G Piza
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. V H J Zepeda
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. J R Mikhael
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. J F Leis
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. P L Bergsagel
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. R Fonseca
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. A K Stewart
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C B Reeder.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Reeder, C., Reece, D., Kukreti, V. et al. Cyclophosphamide, bortezomib and dexamethasone induction for newly diagnosed multiple myeloma: high response rates in a phase II clinical trial. Leukemia 23, 1337–1341 (2009). https://doi.org/10.1038/leu.2009.26

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2009.26

Keywords

This article is cited by

Search

Advanced search

Quick links