Skip to main content
SpringerLink
Log in

Treatment of Newly Diagnosed Multiple Myeloma in Transplant-Eligible Patients

  • Published:
Current Hematologic Malignancy Reports Aims and scope Submit manuscript

Abstract

Treatment of myeloma has changed significantly in the past decade as a result of better understanding of disease biology, more effective treatments, and improved supportive care. Autologous stem cell transplantation (SCT) is an effective treatment for myeloma and remains a critical component in its management. Given the potential impact of therapy on stem cell collection, initial treatment decisions in myeloma still depend on the patient’s transplant eligibility. The goals of initial therapy remain rapid disease control allowing for reversal of disease complications, as well as reduction in the risk of early death—all with minimal toxicity. The introduction of new drugs such as thalidomide, bortezomib, and lenalidomide has enabled us to achieve this goal, and combinations of these drugs have also led to unprecedented response depth. In addition, the newer drugs are being explored as maintenance therapy following SCT. This review summarizes the current approach to the treatment of newly diagnosed myeloma in transplant-eligible patients.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300.

    Article  PubMed  Google Scholar 

  2. •• Kumar SK, Rajkumar SV, Dispenzieri A, et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood 2008;111:2516–20. This study demonstrated improvement in survival in recent years in patients with myeloma. The improved survival is at least in part due to the introduction of new drugs.

    Article  PubMed  CAS  Google Scholar 

  3. • Landgren O, Kyle RA, Pfeiffer RM, et al. Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study. Blood 2009;113:5412–7. This study provided definitive proof that all myeloma patients have a preceding MGUS phase.

    Article  PubMed  CAS  Google Scholar 

  4. Kyle RA, Rajkumar SV. Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia. 2009;23:3–9.

    Article  PubMed  CAS  Google Scholar 

  5. Kumar SK, Mikhael JR, Buadi FK, 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;84:1095–110.

    Article  PubMed  CAS  Google Scholar 

  6. Fonseca R, Barlogie B, Bataille R, et al. Genetics and cytogenetics of multiple myeloma: a workshop report. Cancer Res. 2004;64:1546–58.

    Article  PubMed  CAS  Google Scholar 

  7. Avet-Loiseau H. Role of genetics in prognostication in myeloma. Best Pract Res Clin Haematol. 2007;20:625–35.

    Article  PubMed  CAS  Google Scholar 

  8. Wuilleme S, Robillard N, Lode L, et al. Ploidy, as detected by fluorescence in situ hybridization, defines different subgroups in multiple myeloma. Leukemia. 2005;19:275–8.

    Article  PubMed  CAS  Google Scholar 

  9. Smadja NV, Bastard C, Brigaudeau C, Leroux D, Fruchart C. Groupe Francais de Cytogenetique H. Hypodiploidy is a major prognostic factor in multiple myeloma. Blood. 2001;98:2229–38.

    Article  PubMed  CAS  Google Scholar 

  10. Fonseca R, Harrington D, Oken MM, et al. Biological and prognostic significance of interphase fluorescence in situ hybridization detection of chromosome 13 abnormalities (delta13) in multiple myeloma: an eastern cooperative oncology group study. Cancer Res. 2002;62:715–20.

    PubMed  CAS  Google Scholar 

  11. Avet-Loiseau H, Li JY, Godon C, et al. P53 deletion is not a frequent event in multiple myeloma. Br J Haematol. 1999;106:717–9.

    Article  PubMed  CAS  Google Scholar 

  12. Facon T, Avet-Loiseau H, Guillerm G, et al. Chromosome 13 abnormalities identified by FISH analysis and serum beta2-microglobulin produce a powerful myeloma staging system for patients receiving high-dose therapy. Blood. 2001;97:1566–71.

    Article  PubMed  CAS  Google Scholar 

  13. Greipp PR, San Miguel J, Durie BG, et al. International staging system for multiple myeloma. J Clin Oncol. 2005;23:3412–20.

    Article  PubMed  Google Scholar 

  14. Kumar S. Multiple myeloma—current issues and controversies. Cancer Treat Rev. 2010;36 Suppl 2:S3–11.

    Article  PubMed  Google Scholar 

  15. Attal M, Harousseau JL, Stoppa AM, et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Francais du Myelome. N Engl J Med. 1996;335:91–7.

    Article  PubMed  CAS  Google Scholar 

  16. Child JA, Morgan GJ, Davies FE, et al. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med. 2003;348:1875–83.

    Article  PubMed  CAS  Google Scholar 

  17. Blade J, Rosinol L, Sureda A, et al. High-dose therapy intensification compared with continued standard chemotherapy in multiple myeloma patients responding to the initial chemotherapy: long-term results from a prospective randomized trial from the Spanish cooperative group PETHEMA. Blood. 2005;106:3755–9.

    Article  PubMed  CAS  Google Scholar 

  18. Palumbo A, Bringhen S, Bruno B, et al. Melphalan 200 mg/m(2) versus melphalan 100 mg/m(2) in newly diagnosed myeloma patients: a prospective, multicenter phase 3 study. Blood. 2010;115(10):1873–9.

    Article  PubMed  CAS  Google Scholar 

  19. Kumar SK, Dingli D, Lacy MQ, et al. Autologous stem cell transplantation in patients of 70 years and older with multiple myeloma: results from a matched pair analysis. Am J Hematol. 2008;83:614–7.

    Article  PubMed  Google Scholar 

  20. Rajkumar SV, Hayman S, Gertz MA, et al. Combination therapy with thalidomide plus dexamethasone for newly diagnosed myeloma. J Clin Oncol. 2002;20:4319–23.

    Article  PubMed  CAS  Google Scholar 

  21. Rajkumar SV, Blood E, Vesole D, Fonseca R, Greipp PR. Eastern Cooperative Oncology G. 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;24:431–6.

    Article  PubMed  CAS  Google Scholar 

  22. Rajkumar SV, Rosinol L, Hussein M, et al. Multicenter, randomized, double-blind, placebo-controlled study of thalidomide plus dexamethasone compared with dexamethasone as initial therapy for newly diagnosed multiple myeloma. J Clin Oncol. 2008;26:2171–7.

    Article  PubMed  CAS  Google Scholar 

  23. Cavo M, Zamagni E, Tosi P, et al. Superiority of thalidomide and dexamethasone over vincristine-doxorubicindexamethasone (VAD) as primary therapy in preparation for autologous transplantation for multiple myeloma. Blood. 2005;106:35–9.

    Article  PubMed  CAS  Google Scholar 

  24. Lokhorst HM, Schmidt-Wolf I, Sonneveld P, et al. Thalidomide in induction treatment increases the very good partial response rate before and after high-dose therapy in previously untreated multiple myeloma. Haematologica. 2008;93:124–7.

    Article  PubMed  CAS  Google Scholar 

  25. Morgan GJ, Davies FE, Gregory WM, et al. The addition of thalidomide to the induction treatment of newly presenting myeloma patients increases the CR rate which is likely to translate into improved PFS and OS [abstract]. ASH Annual Meeting Abstracts. 2009;114:352.

    Google Scholar 

  26. Richardson PG, Sonneveld P, Schuster M, 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;110:3557–60.

    Article  PubMed  CAS  Google Scholar 

  27. Jagannath S, Durie BG, Wolf J, et al. Bortezomib therapy alone and in combination with dexamethasone for previously untreated symptomatic multiple myeloma. Br J Haematol. 2005;129:776–83.

    Article  PubMed  CAS  Google Scholar 

  28. • Harousseau JL, Attal M, Avet-Loiseau H, et al. Bortezomib plus dexamethasone is superior to vincristine plus doxorubicin plus dexamethasone as induction treatment prior to autologous stem-cell transplantation in newly diagnosed multiple myeloma: results of the IFM 2005–01 phase III trial. J Clin Oncol 2010;28:4621–29. This was a large phase 3 study that showed superiority of bortezomib plus dexamethasone over a VAD regimen in terms of initial treatment of myeloma prior to SCT.

    Article  PubMed  CAS  Google Scholar 

  29. Oakervee HE, Popat R, Curry N, et al. PAD combination therapy (PS-341/bortezomib, doxorubicin and dexamethasone) for previously untreated patients with multiple myeloma. Br J Haematol. 2005;129:755–62.

    Article  PubMed  CAS  Google Scholar 

  30. Reeder CB, Reece DE, Kukreti V, et al. Cyclophosphamide, bortezomib and dexamethasone induction for newly diagnosed multiple myeloma: high response rates in a phase II clinical trial. Leukemia. 2009;23:1337–41.

    Article  PubMed  CAS  Google Scholar 

  31. Kumar S, Flinn IW, Richardson PG, et al. Novel three- and four-drug combination regimens of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide, for previously untreated multiple myeloma: results from the multi-center, randomized, phase 2 EVOLUTION study [abstract]. ASH Annual Meeting Abstracts. 2010;116:621.

    Google Scholar 

  32. • Sonneveld P, Schmidt-Wolf I, van der Holt B, et al. HOVON-65/GMMG-HD4 randomized phase III trial comparing bortezomib, doxorubicin, dexamethasone (PAD) vs VAD followed by high-dose melphalan (HDM) and maintenance with bortezomib or thalidomide in patients with newly diagnosed multiple myeloma (MM) [abstract]. ASH Annual Meeting Abstracts 2010;116:40. This was the study to examine the role of bortezomib maintenance following autologous SCT in myeloma. The study showed improved OS in patients receiving bortezomib for induction followed by maintenance bortezomib.

    Google Scholar 

  33. Rajkumar SV, Hayman SR, Lacy MQ, et al. Combination therapy with lenalidomide plus dexamethasone (Rev/Dex) for newly diagnosed myeloma. Blood. 2005;106:4050–3.

    Article  PubMed  CAS  Google Scholar 

  34. •• Rajkumar SV, Jacobus S, Callander NS, et al. Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial. Lancet Oncol 2010;11:29–37. This pivotal study demonstrated inferior OS with high doses of dexamethasone combined with lenalidomide, despite better responses compared with weekly dexamethasone. These results changed practice, and high-dose dexamethasone is no longer used in this setting.

    Article  PubMed  CAS  Google Scholar 

  35. Zonder JA, Crowley J, Hussein MA, et al. Lenalidomide and high-dose dexamethasone compared with dexamethasone as initial therapy for multiple myeloma: a randomized Southwest Oncology Group trial (S0232). Blood. 2010;116:5838–41.

    Article  PubMed  CAS  Google Scholar 

  36. Cavo M, Perrone G, Buttignol S, et al. Bortezomib-thalidomide-dexamethasone compared with thalidomide-dexamethasone as induction and consolidation therapy before and after double autologous transplantation in newly diagnosed multiple myeloma: results from a randomized phase 3 study [abstract]. ASH Annual Meeting Abstracts. 2010;116:42.

    Google Scholar 

  37. Richardson PG, Weller E, Lonial S, et al. Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood. 2010;116:679–86.

    Article  PubMed  CAS  Google Scholar 

  38. Kapoor P, Kumar S, Fonseca R, et al. Impact of risk stratification on outcome among patients with multiple myeloma receiving initial therapy with lenalidomide and dexamethasone. Blood. 2009;114:518–21.

    Article  PubMed  CAS  Google Scholar 

  39. Lacy MQ, Gertz MA, Dispenzieri A, 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;82:1179–84.

    Article  PubMed  CAS  Google Scholar 

  40. Fermand JP, Ravaud P, Chevret S, et al. High-dose therapy and autologous peripheral blood stem cell transplantation in multiple myeloma: up-front or rescue treatment? Results of a multicenter sequential randomized clinical trial. Blood. 1998;92:3131–6.

    PubMed  CAS  Google Scholar 

  41. Attal M, Harousseau JL, Facon T, et al. Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med. 2003;349:2495–502.

    Article  PubMed  CAS  Google Scholar 

  42. Cavo M, Tosi P, Zamagni E, 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(17):2434–41.

    Article  PubMed  Google Scholar 

  43. Sonneveld P, van der Holt B, Vellenga E, et al. Intensive versus double intensive therapy in untreated multiple myeloma: final analysis of the HOVON 24 trial [abstract]. Blood (ASH Annual Meeting Abstracts). 2005;106:2545.

    Google Scholar 

  44. Garban F, Attal M, Michallet M, et al. Prospective comparison of autologous stem cell transplantation followed by dose-reduced allograft (IFM99-03 trial) with tandem autologous stem cell transplantation (IFM99-04 trial) in high-risk de novo multiple myeloma. Blood. 2006;107:3474–80.

    Article  PubMed  CAS  Google Scholar 

  45. Bruno B, Rotta M, Patriarca F, et al. A comparison of allografting with autografting for newly diagnosed myeloma. N Engl J Med. 2007;356:1110–20.

    Article  PubMed  CAS  Google Scholar 

  46. • Krishnan A, Pasquini MC, Ewell M, et al. Tandem autologous hematopoietic stem cell transplants (AuHCT) with or without maintenance therapy (auto-auto) versus single AuHCT followed by hla matched sibling non- myeloablative allogeneic HCT (auto-allo) for patients with standard risk (SR) multiple myeloma (MM): results from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0102 Trial [abstract]. ASH Annual Meeting Abstracts 2010;116:41. This important phase 3 trial once again failed to show any benefit for allogeneic SCT in MM compared with tandem autologous SCT.

    Google Scholar 

  47. Attal M, Harousseau JL, Leyvraz S, et al. Maintenance therapy with thalidomide improves survival in patients with multiple myeloma. Blood. 2006;108:3289–94.

    Article  PubMed  CAS  Google Scholar 

  48. Stewart AK, Trudel S, Bahlis NJ, et al. A randomized phase III trial of thalidomide and prednisone as maintenance therapy following autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM): The NCIC CTG MY.10 Trial [abstract]. ASH Annual Meeting Abstracts. 2010;116:39.

    Google Scholar 

  49. Attal M, Lauwers VC, Marit G, et al. Maintenance treatment with lenalidomide after transplantation for MYELOMA: final analysis of the IFM 2005–02 [abstract]. ASH Annual Meeting Abstracts. 2010;116:310.

    Google Scholar 

  50. McCarthy PL, Owzar K, Anderson KC, et al. Phase III intergroup study of lenalidomide versus placebo maintenance therapy following single autologous hematopoietic stem cell transplantation (AHSCT) for multiple myeloma: CALGB 100104 [abstract]. ASH Annual Meeting Abstracts. 2010;116:37.

    Google Scholar 

  51. •• Morgan GJ, Davies FE, Gregory WM, et al. First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX): a randomised controlled trial. Lancet 2010;376:1989–99. This is the first randomized trial to show survival benefit with the use of bisphosphonates. In this trial, patients who did not have any lytic lesions at diagnosis also derived benefit in terms of reduction in skeletal events.

    Article  PubMed  CAS  Google Scholar 

Download references

Disclosure

No potential conflicts of interest relevant to this article were reported.

Author information

Authors and Affiliations

  1. Division of Hematology, Department of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    Shaji Kumar

Authors
  1. Shaji Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shaji Kumar.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kumar, S. Treatment of Newly Diagnosed Multiple Myeloma in Transplant-Eligible Patients. Curr Hematol Malig Rep 6, 104–112 (2011). https://doi.org/10.1007/s11899-011-0083-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11899-011-0083-0

Keywords

Search

Navigation