Blood Reviews
Volume 21, Issue 6 , Pages 301-314 , November 2007

Management of multiple myeloma: The changing landscape

References 

  1. International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of The International Myeloma Working Group. Br J Haematol. 2003;121:749-57.
  2. Kyle RA, Rajkumar SV. Multiple myeloma. N Engl J Med. 2004;351:1060–1877
  3. Greipp PR, San Miguel J, Durie BG, et al. International staging system for multiple myeloma. J Clin Oncol. 2005;23:3412–3420
  4. Fonseca R, Barlogie B, Bataille R, et al. Genetics and cytogenetics of multiple myeloma: a workshop report. Cancer Res. 2004;64:1546–1558
  5. Shaughnessy J, Tian E, Sawyer J, et al. Prognostic impact of cytogenetic and interphase fluorescence in situ hybridization-defined chromosome 13 deletion in multiple myeloma: early results of Total Therapy II. Br J Haematol. 2003;120:44–52
  6. Hideshima T, Bergsagel PL, Kuehl WM, Anderson KC. Advances in biology of multiple myeloma: clinical applications. Blood. 2004;104:607–618
  7. Bergsagel PL, Kuehl WM, Zhan F, Sawyer J, Barlogie B, Shaughnessy J. Cyclin D dysregulation: an early and unifying pathogenic event in multiple myeloma. Blood. 2005;106:296–303
  8. Chng WJ, Santana-Davila R, Van Wier SA, et al. Prognostic factors for hyperdiploid-myeloma: effects of chromosome 13 deletions and IgH translocations. Leukemia. 2006;20:807–813
  9. Chang H, Sloan S, Li D, et al. The t(4;14) is associated with poor prognosis in myeloma patients undergoing autologous stem cell transplant. Br J Haematol. 2004;125:64–68
  10. Chang H, Qi C, Yi QL, Reece D, Stewart AK. p53 gene deletion detected by fluorescence in situ hybridization is an adverse prognostic factor for patients with multiple myeloma following autologous stem cell transplantation. Blood. 2005;105:358–360
  11. Chang H, Qi XY, Saimee 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
  12. Gertz MA, Lacy MQ, Dispenzieri A, et al. Clinical implications of t(11;14)(q13;q32), t(4;14)(p16.3;q32), and -17p13 in myeloma patients treated with high-dose therapy. Blood. 2005;106:2837–2840
  13. Avet-Loiseau H, Attal M, Moreau P, et al. Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myelome. Blood. 2007;109:3489–3495
  14. Rajkumar SV, Blood E, Vesole DH, Fonseca R, Greipp PR Eastern Cooperative Oncology Group. 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;24:431–436
  15. Chanan-Khan AA, Miller KC, McCarthy P, et al. VAD-t (vincristine, adriamycin, dexamethasone and low-dose thalidomide) is an effective initial therapy with high response rates for patients with treatment naı¨ve multiple myeloma (MM) [abstract]. Blood. 2004;104
  16. Hussein MA, Baz R, Srkalovic G, et al. Phase 2 study of pegylated liposomal doxorubicin, vincristine, decreased-frequency dexamethasone, and thalidomide in newly diagnosed and relapsed-refractory multiple myeloma. Mayo Clin Proc. 2006;81:889–895
  17. Hassoun H, Reich L, Lkimek VM, et al. Doxorubicin and dexamethasone followed by thalidomide and dexamethasone is an effective well tolerated initial therapy for multiple myeloma. Br J Haematol. 2006;132:155–161
  18. Badros A, Goloubeva O, Fenton R, et al. Phase I trial of first-line bortezomib/thalidomide plus chemotherapy for induction and stem cell mobilization in patients with multiple myeloma. Clin Lymphoma Myeloma. 2006;7:210–216
  19. Wang M, Delasalle K, Giralt S, Alexanian R. Rapid control of untreated multiple myeloma with bortezomib-thalidomide-dexamethasone followed by early intensive therapy [abstract]. Blood. 2005;106:784;abstract
  20. Williams CD, Bryne JL, Sidra G, Zaman S, Russell NH. Combination chemotherapy with cyclophosphamide, thalidomide and dexamethsone achieves a high response rate in patients with newly diagnosed, VAD-refractory and relapsed myeloma [abstract]. Blood. 2004;104:1499;abstract
  21. Goldschmidt H, Sonneveld P, Breitkruez I, et al. HOVON 50/GMMG-HD3-Trial; phase II study on the effect of thalidomide combined with high dose melaphalan in myeloma patients up to 65 years [abstract]. Blood. 2005;106:424;abstract
  22. Rajkumar SV, Hayman SR, Lacy MQ, et al. Combination therapy with lenalidomide plus dexamethasone (Rev/Dex) for newly diagnosed myeloma. Blood. 2005;106:4050–4053
  23. Jagannath S, Durie BGM, Wolf J, et al. Long-term follow-up of patients treated with bortezomib alone and in combination with dexamethasone as frontline therapy for multiple myeloma [abstract]. Blood. 108. abstract 796.
  24. 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;129:755–762
  25. Harousseau JL, Attal M, Leleu X, et al. Bortezomib plus dexamethasone as induction treatment prior to autologous stem cell transplantation in patients with newly diagnosed multiple myeloma; results of an IFM phase II study. Haematologica. 2006;91:1498–1505
  26. Orlowski RZ, Peterson BL, Sanford B, et al. Bortezomib and pegylated liposomal doxorubicin as induction therapy for adults with symptomatic multiple myeloma: Cancer and Leukemia Group B Study 10301 [abstract]. Blood. 2006;108:797;abstract
  27. Macro M, Divine M, Uzunham Y, et al. Dexamethasone+thalidomide (Dex/Thal) compared to VAD as a pre-transplant treatment in newly diagnosed multiple myeloma (MM): a randomized trial [abstract]. Blood. 2006;108:57;abstract
  28. Harousseau JL, Marit G, Caillot D, et al. VELCADE/Dexamethasone (Vel/Dex) versus VAD as induction treatment prior to autologous stem cell transplantation (ASCT) in newly diagnosed multiple myeloma (MM): an interim analysis of the IFM 2005-01 randomized multicenter phase II trial [abstract]. Blood. 2006;108:56;abstract
  29. Palumbo A, Brighen S, Caravita T, et al. Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: randomised controlled trial. Lancet. 2006;367:825–831
  30. Facon T, Mary J, Harousseau J, et al. Superiority of melphalan-prednisone (MP)+thalidomide (THAL) over MP and autologous stem cell transplantation in the treatment of new diagnosed elderly patients with multiple myeloma [abstract]. J Clin Oncol, 2006 ASCO Annual Meeting Proceedings; Part 1. 24(18S). abstract 1.
  31. Palumbo A, Falco P, Benevolo L, Canepa L, et al. Oral lenalidomide plus melphalan and prednisone (R-MP) for newly diagnosed multiple myeloma [abstract]. J Clin Oncol, 2006 ASCO Annual Meeting Proceedings; Part 1. 24(18S). abstract 7518.
  32. Mateos MV, Hernandez JM, Hernandez MT, et al. Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma: results of a multicenter phase 1–2 study. Blood. 2006;108:2165–2172
  33. Barlogie B, Kyle RA, Anderson KC, et al. Standard chemotherapy compared with high-dose chemoradiotherapy for multiple myeloma: final results of phase III US Intergroup Trial S9321. J Clin Oncol. 2006;20:929–936
  34. Barlogie B, Shaughnessy J, Tricot G, et al. Treatment of multiple myeloma. Blood. 2004;103:20–32
  35. Attal M, Harousseau J-L, Facon T, et al. Single versus double autologous stem-cell transplantation for multiple myeloma. New Engl J Med. 2003;349:2495–2502
  36. Fermand JP, Alberti C, Marolleau JP. Single versus tandem high dose therapy (HDT) supported with autologous stem cell transplantation using unselected or CD-34-enriched ABSC: results of a two by two designed randomized trial in 230 young patients with multiple myeloma [abstract]. The Hematol J. 2003;4(suppl 1):559–560
  37. 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;25:2434–2441
  38. Goldschmidt H. Single vs double high-dose therapy in multiple myeloma: second analysis of the GMMG-HD2 trial. Haematologica. 2005;90(suppl 1):38
  39. Sonneveld P, van der Holt B, Segeren C, et al. Intensive versus double intensive therapy in untreated multiple myeloma: updated analysis of the randomized phase III study HOVON 24 MM [abstract]. Blood. 2004;104:948;abstract
  40. Mikhael JR, Samiee S, Stewart AK, et al. Outcome after second autologous stem cell transplantation as salvage therapy in patients with relapsed multiple myeloma [abstract]. Blood. 2004;104:943;abstract
  41. Abdelkefi A, Ladeh S, Othman TB, et al. Timing of second autologous transplantations in multiple myeloma: results of a multicenter sequential randomized clinical trial [abstract]. Blood. 2006;108:59;abstract
  42. Reece DE, Flomenberg N, Badros A, et al. Update of melphalan 280mg/m2 plus amifostine cytoprotection before autologous stem cell transplantation as part of initial therapy in multiple myeloma patients [abstract]. J Clin Oncol, 2006 ASCO Annual Meeting Proceedings 2006; Part 1. 24(18S). abstract 7608.
  43. Moreau P, Hullin C, Garban F, et al. Tandem autologous stem cell transplantation in high-risk de novo multiple myeloma: final results of the prospective and randomized IFM 99-04 protocol. Blood. 2006;107:397–403
  44. Garban F, Attal M, Michellat M, et al. Prospective comparison of autologous stem cell transplantation followed by dose-reduced allograft (IFM 99-03 trial) with tandem autologous stem cell transplantation (IFM 99-04 trial) in high-risk de novo multiple myeloma. Blood. 2006;107:3474–3480
  45. Hollmig K, Stover J, Talamo G, et al. Addition of bortezomib (VelcadeTM) to high dose melphalan (Vel-Mel) as an effective conditioning regimen with autologous stem cell support in multiple myeloma (MM) [abstract]. Blood. 2004;104:929;abstract
  46. Pineda-Roman M, Fox MH, Hollmig K, et al. Retrospective analysis of fractionated high-dose melphalan (F-MEL), and bortezomib-thalidomide-dexamethasone (VTD) with autotransplant (AT) support for advanced and refractory multiple myeloma (AR-MM) [abstract]. Blood. 2006;108:3102;abstract
  47. Berenson JR, Crowley JJ, Grogan TM, et al. Maintenance therapy with alternate-day prednisone improves survival in multiple myeloma patients. Blood. 2002;99:3163–3168
  48. Attal M, Harousseau J-L, Leyvraz S, et al. Maintenance therapy with thalidomide improves survival in patients with multiple myeloma. Blood. 2006;108:3289–3294
  49. Spencer A, Prince M, Roberts AW, Bradstock KF, Prosser IW. First analysis of the Autralasian Leukaemia and Lymphoma Groups (ALLG) trial of thalidomide and alternate day prednisolone following autologous stem cell transplantation (ASCT) for patients with multiple myeloma (ALLG MM6) [abstract]. Blood. 2006;108:58;abstract
  50. Barlogie B, Tricot V, Anaissie E, et al. Thalidomide and hematopoietic-stem cell transplantation for multiple myeloma. New Engl J Med. 2006;354:1021–1030
  51. Shaughnessy JD, Haessler J, Zeldis J, et al. An update on the role of thalidomide (THAL) in Total Therapy 2 (TT2) for newly diagnosed patients with multiple myeloma (MM): analysis of subgroups defined by standard prognostic factors (SPF) and gene expression profiling (GEP)-derived subgroups [abstract]. Blood. 2006;108:3389;abstract
  52. Barlogie B, Hollmig K, Zangari M, et al. Total Therapy 3 (TT 3) for newly diagnosed myeloma, incorporating velcade into remission induction with DT PACE: early results regarding efficacy, PBSC mobilization and toxicities [abstract]. Blood. 2004;104:538;abstract
  53. Jagannath S, Richardson PG, Sonneveld P, et al. Bortezomib appears to overcome the poor prognosis conferred by chromosome 13 deletion in phase 2 and 3 trials. Leukemia. 2007;21:151–157
  54. Chang H, Trieu Y, Qi X, Xu W, Stewart AK, Reece D. Bortezomib therapy response is independent of cytogenetic abnormalities in relapsed/refractory multiple myeloma. Leuk Res. 2006;Sep 20;[Epub ahead of print].
  55. Alyea E, Weller E, Schlossman R, et al. Outcome of autologous and allogeneic stem cell transplantation for patients with multiple myeloma: impact of graft versus myeloma. Bone Marrow Transplant. 2003;32:1145–1151
  56. Rosinol L, Lahuerta JJ, Sureda A, et al. Feasibility and efficacy of a planned second transplant (“auto” or “mini-allo”) intensification in patients with multiple myeloma not achieving complete remission (CR) or near-CR with a first autologous transplant: results from a Spanish PETHEMA/GEM study. Haematologica. 2005;90(suppl 1):50
  57. Bruno B, Rotta M, Patriarca F, et al. A comparison of allografting with autografting for newly diagnosed myeloma. New Engl J Med. 2007;356:1110–1120
  58. Kumar SK, Therneau TM, Gertz MA, et al. Clinical course of patients with relapsed multiple myeloma. Mayo Clin Proc. 2004;79:867–874
  59. Sirohi B, Powles R, Singhal S, et al. Second high-dose melphalan autografts for myeloma patients relapsing after one autograft: results equivalent to tandem transplantation. Bone Marrow Transplant. 2002;29(suppl 2):S12
  60. Barlogie B, Desikan R, Eddleman P, et al. Extended survival in advanced and refractory multiple myeloma after single-agent thalidomide: identification of prognostic factors in a phase 2 study of 169 patients. Blood. 2001;98:493–494
  61. Dimopoulos MA, Zervas K, Kouvatseas G, et al. Thalidomide and dexamethasone combination for refractory multiple myeloma. Ann Oncol. 2001;12:991–995
  62. Palumbo A, Falco P, Ambrosini MT, et al. Thalidomide plus dexamethasone is an effective salvage regimen for myeloma patients relapsing after autologous transplant. Eur J Haematol. 2005;75:391–395
  63. Hussein MA, Baz R, Srkalovic G, et al. Phase 2 study of pegylated liposomal doxorubicin, vincristine, decreased-frequency dexamethasone, and thalidomide in newly diagnosed and relapsed-refractory multiple myeloma. Mayo Clin Proc. 2006;81:889–895
  64. Hovenga S, Daenen SM, de Wolf JT, et al. Combined thalidomide and cyclophosphamide treatment for refractory or relapsed multiple myeloma patients: a prospective phase II study. Ann Hematol. 2005;84:311–316
  65. Garcia-Sanz R, Gonzalez-Porras JR, Hernandez JM, et al. The oral combination of thalidomide, cyclophosphamide and dexamethasone (ThaCyDex) is effective in relapsed/refractory multiple myeloma. Leukemia. 2004;18:856–863
  66. Offidani M, Gringhen S, Corvatta L, et al. Thalidomide-dexamethasone plus pegylated liposomal doxorubicin vs. thalidomide-dexamethasone; a case-matched study in advanced multiple myeloma. Eur J Haematol. 2007;78:297–302
  67. Hollmig K, Stover J, Talamo G, et al. Bortezomib (Velcade)+adriamycin+thalidomide+dexamethasone (VATD) as an effective regimen in patients with refractory or relapsed multiple myeloma (MM) [abstract]. Blood. 2004;104:2399;abstract
  68. Zangari M, Barlogie B, Burns MJ, et al. Velcade (V)-thalidomide (T)-dexamethasone (D) for advanced and refractory multiple myeloma (MM): long-term follow-up of phase I-II trial UARK 2001–37: superior outcome in patients with normal cytogenetics and no prior T [abstract]. Blood. 2005;106:2552;abstract
  69. Ciolli S, Leoni F, Gigli F, Rigacci L, Bosi A. Low dose velcade, thalidomide and dexamethasone (LD-VTD): an effective regimen for relapsed and refractory multiple myeloma patients. Leuk Lymphoma. 2006;47:171–173
  70. Chanan-Khan A, Padmanabhan S, Miller KC, et al. Final results of a phase II study of bortezomib (Velcade) in combination with liposomal doxorubicin (Doxil) and thalidomide (VDT) demonstrate a sustained high response rates in patients (pts) with relapsed (rel) or refractory (ref) multiple myeloma [abstract]. Blood. 2006;108:3539;abstract
  71. Palumbo A, Ambrosini MT, Benevolo G, et al. Bortezomib, melphalan, prednisone and thalidomide for relapsed multiple myeloma. Blood. 2007;109:2767–2772
  72. Trieu Y, Trudel S, Pond G, et al. Weekly cyclophosphamide and alternate-day prednisone: an effective, convenient, and well tolerated oral treatment for relapsed multiple myeloma after autologous stem cell transplantation. Mayo Clinc Proc. 2005;80:1578–1582
  73. Kropff M, Bisping G, Liebisch P, et al. Bortezomib in combination with high-dose dexamethasone and continuous low-dose oral cyclophosphamide for relapsed multiple myeloma [abstract]. Blood. 2005;106:2549;abstract
  74. Davies FE, Wu P, Srikanth M, et al. The combination of cyclophosphamide, velcade and dexamethasone (CVD) induces high response rates with minimal toxicity compared to velcade alone (V) and velcade plus dexamethasone (VD) [abstract]. Blood. 2006;108:3537;abstract
  75. Reece DE, Piza G, Trudel S, et al. A phase I-II trial of bortezomib plus oral cyclophosphamide and prednisone for relapsed/refractory multiple myeloma [abstract]. Blood. 2006;108:2556;abstract
  76. Morgan GJ, Schey S, Wu P, et al. Lenalidomide (Revlimid) in combination with cyclophosphamide and dexamethsone is an effective regimen for heavily pre-treated myeloma patients [abstract]. Blood. 2006;108:3555;abstract
  77. Richardson PG, Sonneveld P, Schuster MW, et al. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med. 2005;352:2487–2489
  78. Richardson P, Sonneveld P, Schuster M, et al. Bortezomib continues to demonstrate superior efficacy compared with high-dose dexamethasone in relapsed multiple myeloma: updated results of the APEX trial [abstract]. Blood. 2005;106:2547;abstract
  79. Richardson PG, Barlogie B, Berenson J, et al. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med. 2003;348:2609–2617
  80. Jagannath S, Richardson PG, Barlogie B, et al. Bortezomib in combination with dexamethasone for the treatment of patients with relapsed and/or refractory multiple myeloma with less than optimal response to bortezomib alone. Haematologica. 2006;91:151–157
  81. Jakubowiak AJ, Brackett L, Kendall T, et al. Combination therapy with velcade, doxil, and dexamethasone (VDD) for patients with relapsed/refractory multiple myeloma (MM) [abstract]. Blood. 2006;106:3093;abstract
  82. Biehn SE, Moore DT, Voorhees PM, et al. Extended follow-up of outcome measures and analysis of prognostic factors in multiple myeloma patients treated on a phase I study with bortezomib and pegylated liposomal doxorubicin [abstract]. J Clin Oncol. 2006 ASCO Annual Meeting Proceedings; Part 1.24(18S). abstract 7617.
  83. Teoh G, Tan D, Hwang W, et al. Addition of bortezomib to thalidomide, dexamethasone and zoledronic acid (VTD-Z) significantly improves compelte remission rates in patients with relapsed/refractory multiple myeloma. J Clin Oncol. 2006 ASCO Annual Meeting Proceedings; Part 1. 24(18S). abstract 17537.
  84. Berenson JR, Yang HH, Sadler K, et al. A phase I/II trial assessing bortezomib, and melphalan combination therapy for the treatment of patients with relapsed or refractory multiple myeloma. J Clin Oncol. 2006;24:937–944
  85. Popat R, Oakervee HE, Foot , et al. A phase I-II study of bortezomib and low dose intravenous melphalan (BM) for relapsed multiple myeloma [abstract]. Blood. 2005;106:2555;abstract
  86. Terpos E, Anagnostopopoulos A, Kastritis E, et al. The combination of bortezomib, melphalan, dexamethasone and intermittent thalidomide (VMDT) is an effective treatment for relapsed/refractory myeloma: results of a phase II clinical trail [abstract]. Blood. 2005;106:363;abstract
  87. Harousseau JL, Nagler A, Sonneveld P, et al. for the DOXIL-MMY-3001 Investigators. Effect of the combination of pegylated liposomal doxorubicin and bortezomib on time to progression (TTP) and overall survival of patients with relapsed/refractory multiple myeloma compared with bortezomib alone [abstract]. J Clin Oncol 2007 ASCO Annual Meeting Proceedings; Part 1. 25(18S). abstract 8002.
  88. Dimopoulos MA, Spencer A, Attal M, et al. Study of lenalidomide plus dexamethasone versus dexamethasone alone in relapsed or refractory multiple myeloma (MM): results of a phase 3 study (MM-010) [abstract]. Blood. 2005;106:6;abstract
  89. Knight R, DeLap RJ, Zeldis JB. Lenalidomide and venous thrombosis in multiple myeloma. N Engl J Med. 2006;254:2079–2080
  90. Bahlis J, Mansoor A, Lategan JC, et al. Lenalidomide overcomes poor prognosis conferred by deletion of chromosomes 13 and t(4:14) in multiple myeloma: MM016 trial [abstract]. Blood. 2006;108:405;abstract
  91. Reece DE, Masih-Khan E, Chen C, et al. Lenalidomide (Revlimid) +/− corticosteroids in elderly patients with relapsed/refractory multiple myeloma [abstract]. Blood. 2006;108:3550;abstract
  92. Knop S, Gerecke C, Topp MS, et al. Lenalidomide (RevlimidTM), adriamycin and dexamethasone chemotherapy (RAD) is safe and effective in treatment of relapsed multiple myeloma-first results of a German multicenter phase I/II trial [abstract]. Blood. 2006;108:408;abstract
  93. Baz R, Walker E, Karam MA, et al. Lenalidomide and pegylated doxorubicin-based chemotherapy for relapsed or refractory multiple myeloma: safety and efficacy. Ann Oncol. 2006;17:1766–1771
  94. Richardson PF, Jagannath S, Avigan DE, et al. Lenalidomide plus bortezomib (Rev-Vel) in relapsed and/or refractory multiple myeloma (MM): final results of a multicenter phase I trial [abstract]. Blood. 2006;108:405;abstract

PII: S0268-960X(07)00034-3

doi: 10.1016/j.blre.2007.07.001

Blood Reviews
Volume 21, Issue 6 , Pages 301-314 , November 2007

Article Tools