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Current therapeutic strategies for multiple myeloma

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Abstract

The introduction of novel molecular targeting agents against multiple myeloma has dramatically and rapidly changed the therapeutic strategies for this incurable hematologic disease. Novel agents such as thalidomide, bortezomib and lenalidomide have significantly improved the response rate, progression-free survival, and overall survival compared with conventional chemotherapies, and made it easy to control the disease for longer periods of time. Initial therapies for newly diagnosed myeloma patients depend on the individual’s clinical condition. Induction therapy with novel agents and high-dose chemotherapy followed by autologous stem cell transplantation is a standard therapy for newly diagnosed younger myeloma patients. On the other hand, several combinations of novel agents and other drugs (melphalan, prednisone, dexamethasone, etc.) are widely used as initial therapy for transplantation-ineligible myeloma patients. Although the clinical advantage of maintenance therapy after induction therapy has been reported, it is not recommend in routine practice. Maintenance therapy would be an option for some patients. Despite the significant improvements with the use of novel agents, the majority of patients eventually relapse. A number of treatment options including novel agents, which demonstrated marked clinical effects, are reported in the setting of salvage therapy. The choice of appropriate therapy for relapsed or refractory patients must take the disease status or patient status in consideration. Furthermore, a new generation of novel agents such as pomalidomide, carfilzomib or panobinostat has recently become available for relapsed or refractory myeloma. It is necessary to determine the optimal combination of drugs, administration timing and patients to be treated in future clinical trials.

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References

  1. International Myeloma Working Group (2003) Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol 121:749–757

    Article  Google Scholar 

  2. Alexanian R, Bergsagel DE, Migliore PJ et al (1968) Melphalan therapy for plasma cell myeloma. Blood 31:1–10

    CAS  PubMed  Google Scholar 

  3. Myeloma Trialists’ Collaborative Group (1998) Combination chemotherapy versus melphalan plus prednisone as treatment for multiple myeloma: an overview of 6633 patients from 27 randomized trials. J Clin Oncol 16:3832–3842

    Google Scholar 

  4. Koreth J, Cutler CS, Djulbegovic B et al (2007) High-dose therapy with single autologous transplantation versus chemotherapy for newly diagnosed multiple myeloma: a systematic review and meta-analysis of randomized controlled trials. Biol Blood Marrow Transplant 13:183–196

    Article  CAS  PubMed  Google Scholar 

  5. Attal M, Harousseau JL, Stoppa AM et al (1996) A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Français du Myélome. N Engl J Med 335:91–97

    Article  CAS  PubMed  Google Scholar 

  6. Dimopoulos M, Spencer A, Attal M et al (2007) Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med 357:2123–2132

    Article  CAS  PubMed  Google Scholar 

  7. Richardson PG, Sonneveld P, Schuster MW et al (2005) Assessment of Proteasome Inhibition for Extending Remissions (APEX) Investigators. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med 352:2487–2498

    Article  CAS  PubMed  Google Scholar 

  8. Kumar SK, Rajkumar SV, Dispenzieri A et al (2008) Improved survival in multiple myeloma and the impact of novel therapies. Blood 111:2516–2520

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. NCCN clinical practice guidelines in oncology, multiple myeloma version 4.2015. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp#site

  10. Ludwig H, Sonneveld P, Davies F et al (2014) European perspective on multiple myeloma treatment strategies in 2014. Oncologist 19:829–844

    Article  PubMed  Google Scholar 

  11. Palumbo A, Rajkumar SV, San Miguel JF et al (2014) International Myeloma Working Group consensus statement for the management, treatment, and supportive care of patients with myeloma not eligible for standard autologous stem-cell transplantation. J Clin Oncol 32:587–600

    Article  PubMed Central  PubMed  Google Scholar 

  12. Kumar SK, Dispenzieri A, Lacy MQ et al (2014) Continued improvement in survival in multiple myeloma: changes in early mortality and outcomes in older patients. Leukemia 28:1122–1128

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Rajkumar SV, Rosiñol L, Hussein M et al (2008) 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 26:2171–2177

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Rajkumar SV, Jacobus S, Callander NS et al (2010) Eastern Cooperative Oncology Group. 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 11:29–37

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Cavo M, Zamagni E, Tosi P et al (2005) Superiority of thalidomide and dexamethasone over vincristine-doxorubicindexamethasone (VAD) as primary therapy in preparation for autologous transplantation for multiple myeloma. Blood 106:35–39

    Article  CAS  PubMed  Google Scholar 

  16. Morgan GJ, Davies FE, Gregory WM et al (2012) Cyclophosphamide, thalidomide, and dexamethasone as induction therapy for newly diagnosed multiple myeloma patients destined for autologous stem-cell transplantation: MRC Myeloma IX randomized trial results. Haematologica 97:442–450

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Zonder JA, Crowley J, Hussein MA et al (2010) Lenalidomide and high-dose dexamethasone compared with dexamethasone as initial therapy for multiple myeloma: a randomized Southwest Oncology Group trial (S0232). Blood 116:5838–5841

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Sonneveld P, Goldschmidt H, Rosiñol L et al (2013) Bortezomib-based versus nonbortezomib-based induction treatment before autologous stem-cell transplantation in patients with previously untreated multiple myeloma: a meta-analysis of phase III randomized, controlled trials. J Clin Oncol 31:3279–3287

    Article  CAS  PubMed  Google Scholar 

  19. Harousseau JL, Attal M, Avet-Loiseau H et al (2010) 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 28:4621–4629

    Article  CAS  PubMed  Google Scholar 

  20. Nooka AK, Kaufman JL, Behera M et al (2013) Bortezomib-containing induction regimens in transplant-eligible myeloma patients: a meta-analysis of phase 3 randomized clinical trials. Cancer 119:4119–4128

    Article  CAS  PubMed  Google Scholar 

  21. Sonneveld P, Schmidt-Wolf IG, van der Holt B et al (2012) Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/GMMG-HD4 trial. J Clin Oncol 30:2946–2955

    Article  CAS  PubMed  Google Scholar 

  22. Cavo M, Tacchetti P, Patriarca F et al (2010) Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study. Lancet 376:2075–2085

    Article  CAS  PubMed  Google Scholar 

  23. Kumar S, Flinn I, Richardson PG et al (2012) Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma. Blood 119:4375–4382

    Article  CAS  PubMed  Google Scholar 

  24. Richardson PG, Weller E, Lonial S et al (2010) Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood 116:679–686

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Rosiñol L, Oriol A, Teruel AI et al (2012) Superiority of bortezomib, thalidomide, and dexamethasone (VTD) as induction pretransplantation therapy in multiple myeloma: a randomized phase 3 PETHEMA/GEM study. Blood 120:1589–1596

    Article  PubMed  Google Scholar 

  26. Moreau P, Facon T, Attal M et al (2002) Comparison of 200 mg/m2 melphalan and 8 Gy total body irradiation plus 140 mg/m2 melphalan as conditioning regimens for peripheral blood stem cell transplantation in patients with newly diagnosed multiple myeloma: final analysis of the Intergroupe Francophone du Myélome 9502 randomized trial. Blood 99:731–735

    Article  CAS  PubMed  Google Scholar 

  27. Roussel M, Moreau P, Huynh A et al (2010) Bortezomib and high-dose melphalan as conditioning regimen before autologous stem cell transplantation in patients with de novo multiple myeloma: a phase 2 study of the Intergroupe Francophone du Myelome (IFM). Blood 115:32–37

    Article  CAS  PubMed  Google Scholar 

  28. Blanes M, Lahuerta JJ, González JD et al (2013) Intravenous busulfan and melphalan as a conditioning regimen for autologous stem cell transplantation in patients with newly diagnosed multiple myeloma: a matched comparison to a melphalan-only approach. Biol Blood Marrow Transplant 19:69–74

    Article  CAS  PubMed  Google Scholar 

  29. Mark TM, Reid W, Niesvizky R (2013) A phase 1 study of bendamustine and melphalan conditioning for autologous stem cell transplantation in multiple myeloma. Biol Blood Marrow Transplant 19:831–837

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Sonneveld P, van der Holt B, Segeren CM et al (2007) Intermediate-dose melphalan compared with myeloablative treatment in multiple myeloma: long-term follow-up of the Dutch Cooperative Group HOVON 24 trial. Haematologica 92:928–935

    Article  CAS  PubMed  Google Scholar 

  31. Cavo M, Tosi P, Zamagni E (2007) 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

    Article  PubMed  Google Scholar 

  32. Attal M, Harousseau JL, Facon T et al (2003) Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med 349:2495–2502

    Article  CAS  PubMed  Google Scholar 

  33. Cavo M, Pantani L, Petrucci MT et al (2012) Bortezomib-thalidomide-dexamethasone is superior to thalidomide-dexamethasone as consolidation therapy after autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma. Blood 120:9–19

    Article  CAS  PubMed  Google Scholar 

  34. Ladetto M, Pagliano G, Ferrero S et al (2010) Major tumor shrinking and persistent molecular remissions after consolidation with bortezomib, thalidomide, and dexamethasone in patients with autografted myeloma. J Clin Oncol 28:2077–2084

    Article  CAS  PubMed  Google Scholar 

  35. Mellqvist UH, Gimsing P, Hjertner O et al (2013) Bortezomib consolidation after autologous stem cell transplantation in multiple myeloma: a Nordic Myeloma Study Group randomized phase 3 trial. Blood 121:4647–4654

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  36. Attal M, Harousseau JL, Leyvraz S et al (2006) Maintenance therapy with thalidomide improves survival in patients with multiple myeloma. Blood 108:3289–3294

    Article  CAS  PubMed  Google Scholar 

  37. Morgan GJ, Davies FE, Gregory WM et al (2013) Long-term follow-up of MRC Myeloma IX trial: survival outcomes with bisphosphonate and thalidomide treatment. Clin Cancer Res 19:6030–6038

    Article  CAS  PubMed  Google Scholar 

  38. Spencer A, Prince HM, Roberts AW et al (2009) Consolidation therapy with low-dose thalidomide and prednisolone prolongs the survival of multiple myeloma patients undergoing a single autologous stem-cell transplantation procedure. J Clin Oncol 27:1788–1793

    Article  CAS  PubMed  Google Scholar 

  39. Attal M, Lauwers-Cances V, Marit G et al (2012) Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. N Engl J Med 366:1782–1791

    Article  CAS  PubMed  Google Scholar 

  40. McCarthy PL, Owzar K, Hofmeister CC et al (2012) Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med 366:1770–1781

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Palumbo A, Bringhen S, Kumar SK et al (2014) Second primary malignancies with lenalidomide therapy for newly diagnosed myeloma: a meta-analysis of individual patient data. Lancet Oncol 15:333–342

    Article  CAS  PubMed  Google Scholar 

  42. Palumbo A, Cavallo F, Gay F et al (2014) Autologous transplantation and maintenance therapy in multiple myeloma. N Engl J Med 371:895–905

    Article  PubMed  Google Scholar 

  43. National Cancer Institute, Surveillance, Epidemiology, and End Results Program, SEER Stat Fact Sheets: myeloma, number of new cases and deaths. http://seer.cancer.gov/statfacts/html/mulmy.html

  44. Palumbo A, Bringhen S, Liberati AM et al (2008) Oral melphalan, prednisone, and thalidomide in elderly patients with multiple myeloma: updated results of a randomized controlled trial. Blood 112:3107–3114

    Article  CAS  PubMed  Google Scholar 

  45. Wijermans P, Schaafsma M, Termorshuizen F et al (2010) Phase III study of the value of thalidomide added to melphalan plus prednisone in elderly patients with newly diagnosed multiple myeloma: the HOVON 49 Study. J Clin Oncol 28:3160–3166

    Article  CAS  PubMed  Google Scholar 

  46. Facon T, Mary JY, Hulin C et al (2007) Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99-06): a randomised trial. Lancet 370:1209–1218

    Article  CAS  PubMed  Google Scholar 

  47. Hulin C, Facon T, Rodon P et al (2009) Efficacy of melphalan and prednisone plus thalidomide in patients older than 75 years with newly diagnosed multiple myeloma: IFM 01/01 trial. J Clin Oncol 27:3664–3670

    Article  CAS  PubMed  Google Scholar 

  48. Waage A, Gimsing P, Fayers P et al (2010) Melphalan and prednisone plus thalidomide or placebo in elderly patients with multiple myeloma. Blood 116:1405–1412

    Article  CAS  PubMed  Google Scholar 

  49. Beksac M, Haznedar R, Firatli-Tuglular T et al (2011) Addition of thalidomide to oral melphalan/prednisone in patients with multiple myeloma not eligible for transplantation: results of a randomized trial from the Turkish Myeloma Study Group. Eur J Haematol 86:16–22

    Article  CAS  PubMed  Google Scholar 

  50. Fayers PM, Palumbo A, Hulin C et al (2011) Thalidomide for previously untreated elderly patients with multiple myeloma: meta-analysis of 1685 individual patient data from 6 randomized clinical trials. Blood 118:1239–1247

    Article  CAS  PubMed  Google Scholar 

  51. Palumbo A, Falco P, Corradini P et al (2007) Melphalan, prednisone, and lenalidomide treatment for newly diagnosed myeloma: a report from the GIMEMA–Italian Multiple Myeloma Network. J Clin Oncol 25:4459–4465

    Article  CAS  PubMed  Google Scholar 

  52. Palumbo A, Hajek R, Delforge M et al (2012) Continuous lenalidomide treatment for newly diagnosed multiple myeloma. N Engl J Med 366:1759–1769

    Article  CAS  PubMed  Google Scholar 

  53. Benboubker L, Dimopoulos MA, Dispenzieri A et al (2014) Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma. N Engl J Med 371:906–917

    Article  CAS  PubMed  Google Scholar 

  54. San Miguel JF, Schlag R, Khuageva NK et al (2013) Persistent overall survival benefit and no increased risk of second malignancies with bortezomib-melphalan-prednisone versus melphalan-prednisone in patients with previously untreated multiple myeloma. J Clin Oncol 31:448–455

    Article  CAS  PubMed  Google Scholar 

  55. Mateos MV, Richardson PG, Schlag R et al (2010) Bortezomib plus melphalan and prednisone compared with melphalan and prednisone in previously untreated multiple myeloma: updated follow-up and impact of subsequent therapy in the phase III VISTA trial. J Clin Oncol 28:2259–2266

    Article  CAS  PubMed  Google Scholar 

  56. Bringhen S, Larocca A, Rossi D et al (2010) Efficacy and safety of once-weekly bortezomib in multiple myeloma patients. Blood 116:4745–4753

    Article  CAS  PubMed  Google Scholar 

  57. Mateos MV, Oriol A, Martínez-López J et al (2010) Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myeloma: a randomised trial. Lancet Oncol 11:934–941

    Article  CAS  PubMed  Google Scholar 

  58. Moreau P, Pylypenko H, Grosicki S et al (2011) Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study. Lancet Oncol 12:431–440

    Article  PubMed  Google Scholar 

  59. Palumbo A, Bringhen S, Caravita T et al (2006) Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: randomised controlled trial. Lancet 367:825–831

    Article  CAS  PubMed  Google Scholar 

  60. Morgan GJ, Gregory WM, Davies FE et al (2012) The role of maintenance thalidomide therapy in multiple myeloma: MRC Myeloma IX results and meta-analysis. Blood 119:7–15

    Article  CAS  PubMed  Google Scholar 

  61. Palumbo A, Bringhen S, Rossi D et al (2010) Bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomib-melphalan-prednisone for initial treatment of multiple myeloma: a randomized controlled trial. J Clin Oncol 28:5101–5109

    Article  CAS  PubMed  Google Scholar 

  62. Palumbo A, Bringhen S, Larocca A et al (2014) Bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomib-melphalan-prednisone for initial treatment of multiple myeloma: updated follow-up and improved survival. J Clin Oncol 32:634–6340

    Article  CAS  PubMed  Google Scholar 

  63. Cook G, Liakopoulou E, Pearce R et al (2011) Factors influencing the outcome of a second autologous stem cell transplant (ASCT) in relapsed multiple myeloma: a study from the British Society of Blood and Marrow Transplantation Registry. Biol Blood Marrow Transplant 17:1638–1645

    Article  PubMed  Google Scholar 

  64. Mehta J, Singhal S (2007) High-dose chemotherapy and autologous hematopoietic stem cell transplantation in myeloma patients under the age of 65 years. Bone Marrow Transplant 40:1101–1114

    Article  CAS  PubMed  Google Scholar 

  65. Patriarca F, Einsele H, Spina F et al (2012) Allogeneic stem cell transplantation in multiple myeloma relapsed after autograft: a multicenter retrospective study based on donor availability. Biol Blood Marrow Transplant 18:617–626

    Article  CAS  PubMed  Google Scholar 

  66. Kropff M, Baylon HG, Hillengass J et al (2012) Thalidomide versus dexamethasone for the treatment of relapsed and/or refractory multiple myeloma: results from OPTIMUM, a randomized trial. Haematologica 97:784–791

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  67. Knopf KB, Duh MS, Lafeuille MH et al (2014) Meta-analysis of the efficacy and safety of bortezomib re-treatment in patients with multiple myeloma. Clin Lymphoma Myeloma Leuk 14:380–388

    Article  PubMed  Google Scholar 

  68. Madan S, Lacy MQ, Dispenzieri A et al (2011) Efficacy of retreatment with immunomodulatory drugs (IMiDs) in patients receiving IMiDs for initial therapy of newly diagnosed multiple myeloma. Blood 118:1763–1765

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  69. Richardson PG, Sonneveld P, Schuster M et al (2007) Extended follow-up of a phase 3 trial in relapsed multiple myeloma: final time-to-event results of the APEX trial. Blood 110:3557–3560

    Article  CAS  PubMed  Google Scholar 

  70. Richardson P, Jagannath S, Hussein M et al (2009) Safety and efficacy of single-agent lenalidomide in patients with relapsed and refractory multiple myeloma. Blood 114:772–778

    Article  CAS  PubMed  Google Scholar 

  71. Anagnostopoulos A, Weber D, Rankin K et al (2003) Thalidomide and dexamethasone for resistant multiple myeloma. Br J Haematol 121:768–771

    Article  CAS  PubMed  Google Scholar 

  72. Dimopoulos MA, Chen C, Spencer A et al (2009) Long-term follow-up on overall survival from the MM-009 and MM-010 phase III trials of lenalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma. Leukemia 23:2147–2152

    Article  CAS  PubMed  Google Scholar 

  73. San Miguel J, Weisel K, Moreau P et al (2013) Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial. Lancet Oncol 14:1055–1066

    Article  PubMed  Google Scholar 

  74. Stewart AK, Rajkumar SV, Dimopoulos MA et al (2015) Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med 372:142–152

    Article  PubMed  Google Scholar 

  75. San-Miguel JF, Hungria VT, Yoon SS et al (2014) Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: a multicentre, randomised, double-blind phase 3 trial. Lancet Oncol 15:1195–1206

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Oncology Center, Asahikawa Medical University Hospital, 2-1, Midorigaoka-Higashi, Asahikawa, Hokkaido, 078-8510, Japan

    Yoshihiro Torimoto

  2. Division of Gastroenterology and Hematology/Oncology, Department on Internal Medicine, Asahikawa Medical University, 2-1, Midorigaoka-Higashi, Asahikawa, Hokkaido, 078-8510, Japan

    Motohiro Shindo, Katsuya Ikuta & Yutaka Kohgo

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  1. Yoshihiro Torimoto
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Correspondence to Yoshihiro Torimoto.

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Torimoto, Y., Shindo, M., Ikuta, K. et al. Current therapeutic strategies for multiple myeloma. Int J Clin Oncol 20, 423–430 (2015). https://doi.org/10.1007/s10147-015-0826-3

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