Bortezomib as Induction Therapy in Patients with Multiple Myeloma

  • San J. F. Miguel
  • M. V. Mateos
Part of the Contemporary Hematology book series (CH)


In 2006, ~16,570 individuals (9,250 men and 7,320 women) developed multiple myeloma (MM) in the United States, while another 11,310 individuals (5,680 men and 5,630 women) died from the disease. Although deaths from MM accounted for only 2% of all cancer deaths in the United States in 2006, this disease remains as an incurable disease with the worst ratio of deaths to newly diagnosed cases at 4:3.1 Therefore, new treatment approaches are needed to improve patients' outcome. The increased knowledge in MM biology is already contributing to a more specific drug design, and we have recently learned that in the pathogenesis of MM, as important as the malignant plasma cells themselves, is their interaction with the microenvironment.2One novel therapeutic strategy focuses on the proteasome, a large complex of proteolytic enzymes responsible for degradation of ubiquitinated proteins. Bortezomib (Velcade®, Millennium Pharmaceuticals, Inc., and Johnson & Johnson Pharmaceutical...


Multiple Myeloma Complete Response Peripheral Neuropathy Induction Therapy Autologous Stem Cell Transplant 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was partially supported by grants from the Scientific Foundation of Spanish Association against Cancer (AECC), FISS and Myeloma Network (Red de Mieloma G03–136), and SaCyL (Ref 51-05).


  1. 1.
    Jenal A, Murray T, Ward E, et al. Cancer statistics, 2005. CA Cancer J Clin 2005; 55: 10–30.CrossRefGoogle Scholar
  2. 2.
    San Miguel JF, Gutiérrez N, García-Sanz R, et al. Thalidomide and new drugs for treatment of multiple myeloma. Hematol J 2003; 4: 201–7.Google Scholar
  3. 3.
    Richardson P, Chanan-Khan A, Schlossman R, et al. Phase II trial of single agent bortezomib (VELCADE ®) in patients with previously untreated multiple myeloma (MM). Blood 2004; 104(11): Abstract 336.Google Scholar
  4. 4.
    Dispenzieri A, Zhang L, Fonseca R, et al. Single agent bortezomib is associated with a high response rate in patients with high risk myeloma. A phase II study from the Eastern Cooperative Oncology Group (E2A02). Blood 2006; 108(11): Abstract 3527.Google Scholar
  5. 5.
    Jagannath S, Wolf H, Camacho E, et al. Bortezomib therapy alone and in combination with dexamethasone for previously untreated symptomatic multiple myeloma. Br J Haematol 2005; 129: 776–83.PubMedCrossRefGoogle Scholar
  6. 6.
    Jagannath S, Durie B, Wolf H, et al. Long-term follow-up of patients treated with bortezomib alone and in combination with dexamethasone as frontline therapy for multiple myeloma. Blood 2006; 108(11): Abstract 796.Google Scholar
  7. 7.
    Harousseau JL, Attal M, Leleu X, et al. Bortezomib (VELCADE®) plus dexameth-asone as induction treatment prior to autologous stem cell transplantation (ASCT) in patients with newly diagnosed multiple myeloma: preliminary results of an IFM phase II study. Hematologica 2006; 91(11): 1498–505.Google Scholar
  8. 8.
    Harousseau JL, Marit G, Caillot D, et al. VELCADE/dexamethasone (Vel/Dex) versus VA D as induction treatment prior to autologous stem cell transplantation (ASCT) in newly diagnosed multiple myeloma (MM): an interim analysis of the IFM 2005–01 randomized multicenter phase III trial. Blood 2006; 108(11): Abstract 56Google Scholar
  9. 9.
    Rosiñol L, Oriol A, Mateos MV, et al. Alternating bortezomib and dexamethasone as induction regimen prior to autologous stem-cell transplantation in newly diagnosed younger patients with multiple myeloma: results of a PETHEMA phase II trial. Blood 2006; 108(11): Abstract 3086.Google Scholar
  10. 10.
    Ma MH, Yang HH, Parker K, et al. The proteasome inhibitor PS-341 markedly enhances sensitivity of multiple myeloma tumor cells to chemotherapeutic agents. Clin Cancer Res 2003; 9: 1136–44.PubMedGoogle Scholar
  11. 11.
    Mitsiades N, Mitsiades CS, Richardson PG, et al. The proteasome inhibitor PS-341 potentiates sensitivity of multiple myeloma cells to conventional chemotherapeutic agents; therapeutic applications. Blood 2003; 101: 2377–80.PubMedCrossRefGoogle Scholar
  12. 12.
    Oarkowee HE, Popat R, Curry N, et al. PAD combination therapy (PS-341/bort-ezomib, Adriamycin and dexamethasone) for previously untreated patients with multiple myeloma. Br J Haematol 2005; 129:755–62.CrossRefGoogle Scholar
  13. 13.
    Popat R, Oakervee HE, Curry N, et al. Reduced dose PAD combination therapy (PS-341/bortezomib, Adriamycin and dexamethasone) for previously untreated patients with multiple myeloma. Blood 2005; 106(11): Abstract 717.Google Scholar
  14. 14.
    Orlowski RZ, Stinchcombe TE, Mitchell BS, et al. Phase I trial of the proteasome inhibitor PS-341 in patients with refractory hematologic malignancies. J Clin Oncol 2002; 20: 4420–7.PubMedCrossRefGoogle Scholar
  15. 15.
    Orlowski RZ, Peterson BL, Sanford B, et al. Bortezomib/PLD as induction therapy for symptomatic MM; CALGB Study 10301. Blood 2006; 108(11): Abstract 797Google Scholar
  16. 16.
    Jakubowiak AJ, Al-Zoubi A, Kendall T, et al. High rate of complete and near complete responses (CR/nCR) after initial therapy with bortezomib (Velcade ®), Doxil ®, and dexamethasone (VDD) is further increased after autologous stem cell transplantation (ASCT). Blood 2006; 108(11): Abstract 3096Google Scholar
  17. 17.
    Wang M, Delasalle K, Giralt S, and Alexanian R. Rapid control of previously untreated multiple myeloma with bortezomib-thalidomide-dexamethasone followed by early intensive therapy. Blood 2005; 106(11): Abstract 232.Google Scholar
  18. 18.
    Badros A, Goloubeva O, Fenton R, et al. Phase I trial of first-line bortezomib/tha-lidomide plus chemotherapy for induction and stem cell mobilization in patients with multiple myeloma. Clin Lymphoma Myeloma 2006; 7(3): 210–6.PubMedCrossRefGoogle Scholar
  19. 19.
    Mateos MV, Hernández JM, Hernández MT, et al. Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma: results of a multicenter phase I/II trial. Blood 2006; 108: 2165–72.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • San J. F. Miguel
    • 1
  • M. V. Mateos
    • 1
  1. 1.Cancer Research CenterUniversity Hospital of SalemancaSpain

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