Novel therapeutic concepts in multiple myeloma

Short Review


Treatment of multiple myeloma (MM) has evolved greatly over the past decade, and owing to immunomodulatory agents (thalidomide and lenalidomide) and proteasome inhibition (bortezomib), patients with MM enjoy prolonged survival and improved quality of life. Use of these novel agents has improved the rate of complete remissions in MM, a parameter that has emerged as an important step towards improved survival. Bortezomib should now be considered as an established component of the induction treatment prior to autologous transplantation in younger patients. The combination of melphalan/prednisone with a novel agent is a new standard of care for elderly patients with MM. The beneficial effect of these treatment approaches is also seen in special MM populations, in particular in those with impaired renal function and high-risk cytogenetic features.


Myeloma Complete response Thalidomide Bortezomib Lenalidomide 


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  1. Mitsiades CS, McMillin DW, Klippel S, Hideshima T, et al. The role of the bone marrow microenvironment in the pathophysiology of myeloma and its significance in the development of more effective therapies. Hematol Oncol Clin North Am, 21: 1007–1034, 2007PubMedCrossRefGoogle Scholar
  2. Palumbo A, Facon T, Sonneveld P, Blade J, et al. Thalidomide for treatment of multiple myeloma: 10 years later. Blood, 111: 3968–3977, 2008PubMedCrossRefGoogle Scholar
  3. Palumbo A, San Miguel J, Sonneveld P, Moreau P, et al. Lenalidomide: a new therapy for multiple myeloma. Cancer Treat Rev, 34: 283–291, 2008PubMedCrossRefGoogle Scholar
  4. Chauhan D, Hideshima T, Anderson KC. Targeting proteasomes as therapy in multiple myeloma. Adv Exp Med Biol, 615: 251–260, 2008PubMedCrossRefGoogle Scholar
  5. Rajkumar SV, Richardson PG, Hideshima T, Anderson KC. Proteasome inhibition as a novel therapeutic target in human cancer. J Clin Oncol, 23: 630–639, 2005PubMedCrossRefGoogle Scholar
  6. Greipp PR, San Miguel J, Durie BGM, Crowley JJ, et al. International Staging System for multiple myeloma. J Clin Oncol, 23: 3412–3420, 2005PubMedCrossRefGoogle Scholar
  7. Dispenzieri A, Rajkumar V, Gertz MA, Fonseca R, et al. Treatment of newly diagnosed multiple myeloma based on Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART). Mayo Clin Proc, 82: 323–341, 2007PubMedCrossRefGoogle Scholar
  8. Attal M, Harousseau JL, Stoppa AM, Sotto JJ, et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. N Engl J Med, 335: 91–97, 1996PubMedCrossRefGoogle Scholar
  9. Harousseau JL, Attal M, Moreau P, Garban F, et al. The prognostic impact of complete remission (CR) plus very good partial remission (VGPR) in a double-transplantation program for newly diagnosed multiple myeloma. Combined results of the IFM 99 trials. Blood, 108: 877a, 2006 (abstract 3077)Google Scholar
  10. Cavo M, Tosi P, Zamagni E, Cellini C, et al. Prospective, randomized study of single compared with double autologous stem-cell transplantation for multiple myeloma: Bologna 96 clinical study. J Clin Oncol, 25: 2434–2441, 2007PubMedCrossRefGoogle Scholar
  11. Wang M, Delasalle K, Thomas S, Giralt S, Alexanian R. Complete remission represents the major surrogate marker of long survival in multiple myeloma. Blood, 108: 123a, 2006 (abstract 403)CrossRefGoogle Scholar
  12. Kyle RA, Leong T, Li S, Oken MM, et al. Complete response in multiple myeloma: clinical trial E9486, an Eastern Cooperative Oncology Group study not involving stem cell transplantation. Cancer, 106: 1958–1966, 2006PubMedCrossRefGoogle Scholar
  13. Straka C, Liebisch P, Hennemann B, Metzner B, et al. The effects of induction chemotherapy and high-dose melphalan with tandem autologous transplantation in multiple myeloma: the prospective randomized DSMM 2 study. Blood, 110: 138a, 2007 (abstract 446)Google Scholar
  14. Harousseau JL, Mathiot C, Attal M, Marit G, et al. Bortezomib/dexamethasone versus VAD as induction prior to autologous stem cell transplantation in previously untreated multiple myeloma: updated data from IFM 2005/01 trial. ASCO Proc, 26: 455s, 2008 (abstract 8505)Google Scholar
  15. Cavo M, Patriarca F, Tacchetti P, Galli M, et al. Bortezomib (Velcade)-Thalidomide-Dexamethasone (VTD) in preparation for autologous stem-cell transplantation in newly diagnosed multiple myeloma. Blood, 110: 30a, 2007 (abstract 73)Google Scholar
  16. Rajkumar SV, Jacobus S, Callander N, Fonseca R, et al. Randomized trial of lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone in newly diagnosed myeloma (E4A03), a trial coordinated by the Eastern Cooperative Oncology Group: analysis of response, survival and outcome. ASCO Proc, 26: 455s, 2008 (abstract 8504)Google Scholar
  17. Kumar S, Dispenzieri A, Lacy MQ, Hayman SR, et al. Impact of lenalidomide therapy on stem cell mobilization and engraftment post-peripheral stem cell transplantation in patients with newly diagnosed myeloma. Leukemia, 21: 2035–2042, 2007PubMedCrossRefGoogle Scholar
  18. Paripati H, Stewart AK, Cabou S, Dueck A, et al. Compromised stem cell mobilization following induction therapy with lenalidomide in myeloma. Leukemia, 22: 1282–1284, 2008PubMedCrossRefGoogle Scholar
  19. Mark T, Stern J, Furst JR, Jayabalan D, et al. Stem cell mobilization with cyclophosphamide overcomes the suppressive effect of lenalidomide therapy on stem cell collection in multiple myeloma. Biol Blood Marrow Transplant, 14: 795–798, 2008PubMedCrossRefGoogle Scholar
  20. Facon T, Mary JH, Hulin C, Benboubker L, et al. Melphalan and prednisone plus thalidomide versus melphalan plus prednisone alone or reduced intensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99-06): a randomized trial. Lancet, 370: 1209–1218, 2007PubMedCrossRefGoogle Scholar
  21. Hulin C, Facon T, Rodon P, Pegourie B, et al. Melphalan-prednisone-Thalidomide (MP-T) demonstrates a significant survival advantage in elderly patients ≥75 years with multiple myeloma compared with Melphalan-Prednisone (MP) in a randomized, double-blind, placebo-controlled trial, IFM 01/01, Blood, 110: 31a, 2007 (abstract 75)Google Scholar
  22. Palumbo A, Bringhen S, Liberati AM, Caravita T, et al. Oral melphalan, prednisone, and thalidomide in elderly patients with multiple myeloma: updated results of a randomized controlled trial. Blood, 112: 3107–3114, 2008PubMedCrossRefGoogle Scholar
  23. Gulbrandsen N, Waage A, Gimsing P, Turesson I, et al. A randomized placebo controlled study with melphalan/prednisone vs melphalan/prednisone/thalidomide: quality of life and toxicity. Haematologica, 93(Suppl 1): 84, 2008 (abstract 209)Google Scholar
  24. Wijermans P, Schaafsma M, van Norden Y, Ammerlaan R, et al. Melphalan+prednisone vs melphalan+prednisone+thalidomide in induction therapy for multiple myeloma in elderly patients: first interim results of the Dutch cooperative group HOVON. Haematologica, 93(Suppl 1): 178, 2008 (abstract 440)Google Scholar
  25. Barlogie B, Tricot G, Anaissie E, Shaughnessy J, et al. Thalidomide and hematopoietic-cell transplantation for multiple myeloma. N Engl J Med, 354: 1021–1030, 2006PubMedCrossRefGoogle Scholar
  26. Ludwig H, Tothova E, Hajek R, Drach J, et al. Thalidomide-Dexamethasone vs. Melphalan-Prednisone as first line treatment and thalidomide-interferon vs. interferon maintenance therapy in elderly patients with multiple myeloma. Blood, 110: 163a, 2007 (abstract 529)Google Scholar
  27. San Miguel J, Schlag R, Khuageva N, Dimopoulos M, et al. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med, 359: 906–917, 2008PubMedCrossRefGoogle Scholar
  28. Attal M, Harousseau JL, Leyvraz S, Doyen C, et al. Maintenance therapy with thalidomide improves survival in patients with multiple myeloma. Blood, 108: 3289–3294, 2006PubMedCrossRefGoogle Scholar
  29. Abdelkefi A, Ladeb S, Torjman L, Othman TB, et al. Single autologous transplantation followed by maintenance therapy with thalidomide is superior to double autologous transplantation in multiple myeloma: results of a multicenter randomized clinical trial. Blood, 111: 1805–1810, 2008PubMedCrossRefGoogle Scholar
  30. Ludwig H, Adam Z, Greil R, Keil F, et al. Recovery of renal impairment by bortezomib-doxorubicin-dexamethasone (BDD) in multiple myeloma patients with acute renal failure. Results from an ongoing phase II study. Haematologica, 93(Suppl 1): 177, 2008, (abstract 439)Google Scholar
  31. Roussou M, Kastritis E, Migkou M, Psimenou E, et al. Treatment of patients with multiple myeloma complicated by renal failure with bortezomib-based regimens. Leuk Lymphoma, 49: 890–895, 2008PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  1. 1.Clinical Division of Oncology, Department of Medicine IMedical University of ViennaViennaAustria

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