Skip to main content
Log in

Bortezomib and dexamethasone for Japanese patients with relapsed and refractory multiple myeloma: a single center experience

  • Original Article
  • Published:
International Journal of Hematology Aims and scope Submit manuscript

Abstract

Bortezomib is a novel proteasome inhibitor, which has shown high antimyeloma activity. APEX trial, phase III randomized study for relapsed or refractory myeloma established efficacy and feasibility of bortezomib. In our study, we retrospectively investigated 60 Japanese patients with relapsed or refractory multiple myeloma (MM) who underwent bortezomib and dexamethasone (BD) therapy in our institution. Overall response rate was 75%, including 7 cases (11.7%) of complete response and 13 cases (21.7%) of very good partial response. Stable disease and progressive disease were observed in 15 patients (25%). Major ≥grade 3 adverse events were hematological toxicities and grade 3 non-hematological toxicities included appetite loss, diarrhea and peripheral neuropathy. BD therapy was well tolerated, and produced significant response in relapsed or refractory MM patients. Recently, many worldwide trials including bortezomib or other new agents are ongoing to evaluate its efficacy not only as a therapy for relapsed or refractory disease but also as a frontline therapy. Further investigations are required to define how to use new antimyeloma agents for Japanese MM patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Richardson PG, Barlogie B, Berenson J, Singhal S, Jagannath S, Irwin D, et al. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med. 2003;348(26):2609–17.

    Article  CAS  PubMed  Google Scholar 

  2. Jagannath S, Barlogie B, Berenson J, Siegel D, Irwin D, Richardson PG. A phase 2 study of two doses of bortezomib in relapsed or refractory myeloma. Br J Haematol. 2004;127(2):165–72.

    Article  CAS  PubMed  Google Scholar 

  3. Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer EA, Facon T, Assessment of Proteasome Inhibition for Extending Remissions (APEX) Investigators, et al. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med. 2005;352(24):2487–98.

    Article  CAS  PubMed  Google Scholar 

  4. Ogawa Y, Tobinai K, Ogura M, Ando K, Tsuchiya T, Kobayashi Y, et al. Phase I and II pharmacokinetic and pharmacodynamic study of the proteasome inhibitor bortezomib in Japanese patients with relapsed or refractory multiple myeloma. Cancer Sci. 2008;99(1):140–4.

    CAS  PubMed  Google Scholar 

  5. Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF, et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroup Français du Myélome. N Engl J Med. 1996;335(2):91–7.

    Article  CAS  PubMed  Google Scholar 

  6. Child JA, Morgan GJ, Davies FE, Owen RG, Bell SE, Hawkins K, et al. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med. 2003;348(19):1875–83.

    Article  CAS  PubMed  Google Scholar 

  7. Bladé J, Samson D, Reece D, Apperley J, Björkstrand B, Gahrton G, et al. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant. Br J Haematol. 1998;102(5):1115–23.

    Article  PubMed  Google Scholar 

  8. Durie BG, Harousseau JL, Miguel JS, Bladé J, Barlogie B, Anderson K, et al. International uniform response criteria for multiple myeloma. Leukemia. 2006;20(9):1467–73.

    Google Scholar 

  9. Jagannath S, Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer EA, et al. Bortezomib appears to overcome the poor prognosis conferred by chromosome 13 deletion in phase 2 and 3 trials. Leukemia. 2007;21(1):151–7.

    Article  CAS  PubMed  Google Scholar 

  10. Richardson PG, Sonneveld P, Schuster M, Irwin D, Stadtmauer E, Facon T, et al. Extended follow-up of a phase 3 trial in relapsed multiple myeloma: final time-to-event results of the APEX trial. Blood. 2007;110(10):3557–60.

    Article  CAS  PubMed  Google Scholar 

  11. Argyriou AA, Iconomou G, Kalofonos HP. Bortezomib-induced peripheral neuropathy in multiple myeloma: a comprehensive review of the literature. Blood. 2008;112(5):1593-9.

    Google Scholar 

  12. Palumbo A, Sezer O, Kyle R, Miguel JS, Orlowski RZ, Moreau P, et al. International Myeloma Working Group guidelines for the management of multiple myeloma patients ineligible for standard high-dose chemotherapy with autologous stem cell transplantation. Leukemia. 2009;23(10):1716–30.

    Article  CAS  PubMed  Google Scholar 

  13. Hasegawa Y, Kawahara F, Nagai H, Hirose T, Imai Y, Ishiguro T, et al. Prophylaxis with acyclovir for herpes zoster infection during bortezomib–dexamethasone combination therapy. Rinsho Ketsueki. 2009;50(6):488–94.

    PubMed  Google Scholar 

  14. Chanan-Khan A, Sonneveld P, Schuster MW, Stadtmauer EA, Facon T, Harousseau JL, et al. Analysis of herpes zoster events among bortezomib-treated patients in the phase III APEX study. J Clin Oncol. 2008;26(29):4784–90.

    Article  CAS  PubMed  Google Scholar 

  15. Tong Y, Qian J, Li Y, Meng H, Jin J. The high incidence of varicella herpes zoster with the use of bortezomib in 10 patients. Am J Hematol. 2007;82(5):403–4.

    Google Scholar 

  16. Kropff M, Bisping G, Schuck E, Liebisch P, Lang N, Hentrich M, et al. Bortezomib in combination with intermediate-dose dexamethasone and continuous low-dose oral cyclophosphamide for relapsed multiple myeloma. Br J Haematol. 2007;138(3):330–7.

    Article  CAS  PubMed  Google Scholar 

  17. Mateos MV, Hernández JM, Hernández MT, Gutiérrez NC, Palomera L, Fuertes M, et al. Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma: results of a multicenter phase 1/2 study. Blood. 2006;108(7):2165–72.

    Article  CAS  PubMed  Google Scholar 

  18. 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(8):3115–21.

    Article  CAS  PubMed  Google Scholar 

  19. Barlogie B, Anaissie E, Haessler J, van Rhee F, Pineda-Roman M, Hollmig K, et al. Complete remission sustained 3 years from treatment initiation is a powerful surrogate for extended survival in multiple myeloma. Cancer. 2008;113(2):355–9.

    Article  PubMed  Google Scholar 

  20. Lahuerta JJ, Mateos MV, Martínez-López J, Rosiñol L, Sureda A, de la Rubia J, et al. Influence of pre- and post-transplantation responses on outcome of patients with multiple myeloma: sequential improvement of response and achievement of complete response are associated with longer survival. J Clin Oncol. 2008;26(35):5775–82.

    Google Scholar 

  21. Hoering A, Crowley J, Shaughnessy JD Jr, Hollmig K, Alsayed Y, Szymonifka J, et al. Complete remission in multiple myeloma examined as time-dependent variable in terms of both onset and duration in Total Therapy protocols. Blood. 2009;114(7):1299–305.

    Article  CAS  PubMed  Google Scholar 

  22. Kim JS, Kim K, Cheong JW, Min YH, Suh C, Kim H, Korean Multiple Myeloma Working Party, et al. Complete remission status before autologous stem cell transplantation is an important prognostic factor in patients with multiple myeloma undergoing upfront single autologous transplantation. Biol Blood Marrow Transplant. 2009;15(4):463–70.

    Article  CAS  PubMed  Google Scholar 

  23. Niesvizky R, Richardson PG, Rajkumar SV, Coleman M, Rosiñol L, Sonneveld P, et al. The relationship between quality of response and clinical benefit for patients treated on the bortezomib arm of the international, randomized, phase 3 APEX trial in relapsed multiple myeloma. Br J Haematol. 2008;143(1):46–53.

    Article  CAS  PubMed  Google Scholar 

  24. Paiva B, Vidriales MB, Cerveró J, Mateo G, Pérez JJ, Montalbán MA, GEM (Grupo Español de MM)/PETHEMA (Programa para el Estudio de la Terapéutica en Hemopatías Malignas) Cooperative Study Groups, et al. Multiparameter flow cytometric remission is the most relevant prognostic factor for multiple myeloma patients who undergo autologous stem cell transplantation. Blood. 2008;112(10):4017–23.

    Article  CAS  PubMed  Google Scholar 

  25. van de Velde HJ, Liu X, Chen G, Cakana A, Deraedt W, Bayssas M. Complete response correlates with long-term survival and progression-free survival in high-dose therapy in multiple myeloma. Haematologica. 2007;92(10):1399–406.

    Article  PubMed  Google Scholar 

  26. Rajkumar SV, Fonseca R, Dispenzieri A, Lacy MQ, Witzig TE, Lust JA, et al. Effect of complete response on outcome following autologous stem cell transplantation for myeloma. Bone Marrow Transplant. 2000;26(9):979–83.

    Article  CAS  PubMed  Google Scholar 

  27. Pineda-Roman M, Bolejack V, Arzoumanian V, Anaissie E, van Rhee F, Zangari M, et al. Complete response in myeloma extends survival without, but not with history of prior monoclonal gammopathy of undetermined significance or smouldering disease. Br J Haematol. 2007;136(3):393–9.

    Article  PubMed  Google Scholar 

  28. Durie BG, Russell DH, Salmon SE. Reappraisal of plateau phase in myeloma. Lancet. 1980;2(8185):65–8.

    Article  CAS  PubMed  Google Scholar 

  29. Corso A, Nozza A, Lazzarino M, Klersy C, Zappasodi P, Arcaini L, et al. Plateau phase in multiple myeloma: an end-point of conventional-dose chemotherapy. Haematologica. 1999;84(4):336–41.

    CAS  PubMed  Google Scholar 

  30. Hari P, Pasquini MC, Vesole DH. Cure of multiple myeloma—more hype, less reality. Bone Marrow Transplant. 2006;37(1):1–18.

    CAS  PubMed  Google Scholar 

  31. Stewart AK, Richardson PG, San-Miguel JF. How I treat multiple myeloma in younger patients. Blood. 2009;114(27):5436–43.

    Google Scholar 

  32. Kumar SK, Mikhael JR, Buadi FK, Dingli D, Dispenzieri A, Fonseca R, et al. Management of newly diagnosed symptomatic multiple myeloma: updated Mayo stratification of myeloma and risk-adapted therapy (mSMART) consensus guidelines. Mayo Clin Proc. 2009;84(12):1095–110.

    Article  CAS  PubMed  Google Scholar 

  33. Attal M, Harousseau JL, Facon T, Guilhot F, Doyen C, Fuzibet JG, et al. Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med. 2003;349(26):2495–502.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Natsue Igarashi.

About this article

Cite this article

Igarashi, N., Chou, T., Hirose, T. et al. Bortezomib and dexamethasone for Japanese patients with relapsed and refractory multiple myeloma: a single center experience. Int J Hematol 92, 518–523 (2010). https://doi.org/10.1007/s12185-010-0690-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-010-0690-x

Keywords

Navigation