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

Bortezomib in relapsed multiple myeloma: response rates and duration of response are independent of a chromosome 13q-deletion

Leukemia volume 21, pages 164–168 (2007)Cite this article

Abstract

Studies of bortezomib in patients with relapsed multiple myeloma (MM) suggested that bortezomib may be active even in the presence of adverse prognostic factors. We therefore evaluated 62 patients with relapsed/refractory MM who were treated with single-agent bortezomib, and addressed the question whether or not the negative prognostic impact of unfavorable cytogenetic abnormalities may be overcome by bortezomib. By interphase fluorescence in situ hybridization (FISH), a deletion of chromosome 13q14 [del(13q14)] was present in 33 patients (53%). Overall response rates to bortezomib were similar in patients with and without del(13q14) (45 versus 55%; P=0.66), and rates of complete remission (CR) near CR were also not different between the two patient populations (18 versus 14%). Three patients had a t(4;14)(p16;q32) in addition to del(13q14), and all of them had a >50% paraprotein reduction. Median duration of response was 12.3 months in patients with del(13q14) compared with 9.3 months in patients with normal 13q-status (P=0.25), and survival was also not different between the two patient populations. Patients not benefiting from single-agent bortezomib were characterized by the combined presence of a del(13q14) and low serum albumin (median survival 4.6 months). Our results provide evidence for remarkable activity of bortezomib in MM with del(13q14). Patients who do not respond to bortezomib and consecutively have short time to treatment failure and overall survival can be identified by low serum albumin in addition to del(13q14) and should be considered for bortezomib combinations.

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
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Attal M, Harousseau J-L, Stoppa A-M, Sotto J-L, Fuzibet J-G, Rossi J-F et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. New Engl J Med 1996; 335: 91–97.

    Article  CAS  PubMed  Google Scholar 

  2. 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: 1875–1883.

    Article  CAS  PubMed  Google Scholar 

  3. Adams J, Palombella VJ, Sausville EA, Johnson J, Destree A, Lazarus DD et al. Proteasome inhibitors: a novel class of potent and effective antitumor agents. Cancer Res 1999; 95: 2615–2622.

    Google Scholar 

  4. Hideshima T, Richardson P, Chauhan D, Palombella VJ, Elliott PJ, Adams J et al. The proteasome inhibitor PS-341 inhibits growth, induces apoptosis, and overcomes drug resistance in human multiple myeloma cells. Cancer Res 2001; 61: 3071–3076.

    CAS  PubMed  Google Scholar 

  5. LeBlanc R, Catley LP, Hideshima T, Lentzsch S, Mitsiades CS, Mitsiades N et al. Proteasome inhibitor PS-341 inhibits human myeloma cell growth in vivo and prolongs survival in a murine model. Cancer Res 2002; 62: 4996–5000.

    CAS  PubMed  Google Scholar 

  6. Mitsiades N, Mitsiades CS, Richardson PG, Poulaki V, Tai Y-T, Chauhan D et al. The proteasome inhibitor PS-341 potentiates sensitivity of multiple myeloma cells to conventional chemotherapeutic agents: therapeutic applications. Blood 2003; 101: 2377–2380.

    Article  CAS  PubMed  Google Scholar 

  7. 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: 2609–2617.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  9. Richardson PG, Barlogie B, Berenson J, Singhal S, Jagannath S, Irwin D et al. Clinical factors predictive of outcome with bortezomib in patients with relapsed, refractory multiple myeloma. Blood 2005; 106: 2977–2981.

    Article  CAS  PubMed  Google Scholar 

  10. Greipp PR, Lust JA, O’Fallon WM, Katzmann JA, Witzig TE, Kyle RA et al. Plasma cell labeling index and beta 2-microglobulin predicr survival independent of thymidine kinase and C-reactive protein in multiple myeloma. Blood 1993; 81: 3382–3387.

    CAS  PubMed  Google Scholar 

  11. Facon T, Avet-Loiseau H, Guillerm G, Moreau P, Genevieve F, Zandecki M et al. Chromosome 13 abnormalities identified by FISH analysis and serum beta 2-microglobulin produce a powerful myeloma staging system for patients receiving high-dose therapy. Blood 2001; 97: 1566–1571.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  13. Desikan R, Barlogie B, Sawyer J, Ayers D, Tricot G, Badros A et al. Results of high-dose therapy for 1000 patients with multiple myeloma: durable complete remissions and superior survival in the absence of chromosome 13 abnormalities. Blood 2000; 95: 4008–4010.

    CAS  PubMed  Google Scholar 

  14. Zojer N, Königsberg R, Ackermann J, Fritz E, Dallinger S, Krömer E et al. Deletion of 13q14 remains an independent adverse prognostic variable in multiple myeloma despite its frequent detection by interphase fluorescence in situ hybridisation. Blood 2000; 95: 1925–1930.

    CAS  PubMed  Google Scholar 

  15. Fonseca R, Harrington D, Oken MM, Dewald GW, Bailey RJ, Van Wier SA et al. Biological and prognostic significance of interphase fluorescence in situ hybridization detection of chromosome 13 abnormalities (Δ13) in multiple myeloma: an Eastern Cooperative Oncology Group study. Cancer Res 2002; 62: 715–720.

    CAS  PubMed  Google Scholar 

  16. Fonseca R, Barlogie B, Bataille R, Bastard C, Bergsagel PL, Chesi M et al. Genetics and cytogenetics of multiple myeloma: a workshop report. Cancer Res 2004; 64: 1546–1558.

    Article  CAS  PubMed  Google Scholar 

  17. Kroeger N, Schilling G, Einsele H, Liebisch P, Simoni A, Nagler A et al. Deletion of chromosome band 13q14 as detected by FISH is a prognostic factor in patients with multiple myeloma who are receiving allogeneic dose-reduced stem cell transplantation. Blood 2004; 103: 4056–4061.

    Article  CAS  Google Scholar 

  18. Durie BGM, Salmon SE . A clinial staging system for multiple myeloma. Cancer 1975; 36: 842–854.

    Article  CAS  PubMed  Google Scholar 

  19. Blade J, Samson D, Reece D, Apperley J, Bjorkstrand B, Garton 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: myeloma subcommittee of the EBMT. Br J Haematol 1998; 102: 1115–1123.

    Article  CAS  PubMed  Google Scholar 

  20. Ackermann J, Meidlinger P, Zojer N, Gisslinger H, Ludwig H, Huber H et al. Absence of p53 deletions in bone marrow plasma cells of patients with monoclonal gammopathy of undetermined significance. Br J Haematol 1998; 103: 1161–1163.

    Article  CAS  PubMed  Google Scholar 

  21. Kaufmann H, Ackermann J, Baldia C, Nosslinger T, Wieser R, Seidl S et al. Both IGH translocations and chromosome 13q deletions are early events in monoclonal gammopathy of undetermined significance and do not evolve during transition to multiple myeloma. Leukemia 2004; 18: 1879–1882.

    Article  CAS  PubMed  Google Scholar 

  22. Moreau P, Facon T, Leleu X, Morineau N, Huyghe P, Harousseau JL et al. Recurrent 14q32 translocations determine the prognosis of multiple myeloma, especially in patients receiving intensive chemotherapy. Blood 2002; 100: 1579–1583.

    Article  CAS  PubMed  Google Scholar 

  23. Gertz MA, Lacy MQ, Disperenzieri A, Greipp PR, Litzow MR, Henderson KJ et al. Clinical impact of t(11;14)(q13;q32), t(4;14)(p16.3;q32) and −17p53 in myeloma patients treated with high-dose therapy. Blood 2005; 106: 2837–2840.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Chang H, Qi XY, Samiee S, Yi OL, Chen C, Trudel S et al. Genetic risk identifies multiple myeloma patients who do not benefit from autologous stem cell transplantation. Bone Marrow Transplant 2005; 36: 793–796.

    Article  CAS  PubMed  Google Scholar 

  25. Jaksic W, Trudel S, Chang H, Trieu Y, Qi X, Mikhael J et al. Clinical outcome in t(4;14) multiple myeloma: a chemotherapy-sensitive disease characterized by rapid relapse and alkylating agent resistance. J Clin Oncol 2005; 23: 7069–7073.

    Article  CAS  PubMed  Google Scholar 

  26. Barlogie B, Desikan R, Eddlemon P, Spencer T, Zeldis J, Munshi N et al. Extended survival in advanced and refractory mutiple myeloma after single-agent thalidomide: identification of prognostic factors in a phase 2 study of 169 patients. Blood 2001; 98: 492–494.

    Article  CAS  PubMed  Google Scholar 

  27. Shaughnessy J, Tian E, Sawyer J, McCoy J, Tricot G, Jacobson J et al. Prognostic impact of cytogenetics and interphase FISH-defined chromosome 13 deletion in multiple myeloma: early results of total therapy II. Br J Haematol 2003; 120: 44–52.

    Article  PubMed  Google Scholar 

  28. Dewald GW, Therneau T, Larson D, Lee YK, Fink S, Smoley S et al. Relationship of patient survival and chromosome anomalities detected in metaphase and/or interphase cells at diagnosis of myeloma. Blood 2005; 106: 3553–3558.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Shaughnessy J, Zhan F, Barlogie B, Stewart AK . Gene expression profiling and multiple myeloma. Best Pract Res Clin Haematol 2005; 18: 537–552.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the Austrian Federal Ministry for Education, Science and Culture (GZ 200.062/2-VI/1/2002). Presented in part at the 47th Annual Meeting of the American Society of Hematology, Atlanta, GA, USA December 10–13, 2005.

Author information

Authors and Affiliations

  1. Department of Internal Medicine I, Clinical Division of Oncology, Medical University of Vienna, Vienna, Austria

    V Sagaster, H Kaufmann, V Odelga, J Ackermann, C Zielinski & J Drach

  2. Department of Medicine I, Centre of Oncology and Hematology, Wilhelminenspital, Vienna, Austria

    H Ludwig, N Zojer & E Küenburg

  3. Division of Human Genetics, Medical University of Vienna, Vienna, Austria

    R Wieser

Authors
  1. V Sagaster
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H Ludwig
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H Kaufmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. V Odelga
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. N Zojer
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J Ackermann
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. E Küenburg
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. R Wieser
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. C Zielinski
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. J Drach
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J Drach.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sagaster, V., Ludwig, H., Kaufmann, H. et al. Bortezomib in relapsed multiple myeloma: response rates and duration of response are independent of a chromosome 13q-deletion. Leukemia 21, 164–168 (2007). https://doi.org/10.1038/sj.leu.2404459

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2404459

Keywords

This article is cited by

Search

Advanced search

Quick links