Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Treatment of Multiple Myeloma

Current Management and New Approaches

  • 11 Accesses

Abstract

The management of multiple myeloma (MM) has undergone many developments in the last 30 years. Initially, melphalan was used as a single agent and this was followed by the discovery of corticosteroids as highly active agents and the design of multiagent cytotoxic regimens. However, although response rates have improved, little impact has been achieved on survival. Interferon has been extensively examined in early as well as relapsed disease. Currently, a benefit in survival is only evident in maintenance phase, where there is a small but significant difference. However, this has to be evaluated in the context of adverse effects and the impact on quality of life.

In recent years, autologous stem cell transplantation has become established as the standard therapy for eligible patients. An advantage in survival has been established in at least one randomized trial, and response rates have been improved. Unfortunately, relapse after an auto transplant is almost inevitable, and the possible benefits of more than one transplant continue to be examined. To date, allotransplantation has assumed a much smaller role in MM, predominantly because of a high transplant-related mortality (TRM). An important innovation has been the use of donor lymphocyte infusions to harness the graft versus myeloma effect, either in relapse after allogeneic transplantation or in the novel strategy of nonmyeloablative allotransplants, with the aim of reducing TRM and increasing the eligibility of patients for allogeneic transplantation. Thalidomide, which has immunomodulatory and antiangiogenic properties, has been used as a single agent or in combination with other cytotoxic regimens in relapsed/ refractory disease, with response rates of approximately 30%. Its role in early disease is currently being evaluated. Bisphosphonates are now established as standard therapy in myeloma bone disease and are associated with the reduction of skeletal complications. Possible benefits in early ‘smoldering’ disease and effects on survival continue to be evaluated. Immunotherapy is one of the most intensely studied and promising developments in myeloma management. A variety of techniques ranging from tumor vaccination to the use of monoclonal antibodies are under active evaluation. Other experimental agents include the development of proteosome inhibitors, immunomodulatory thalidomide analogs, other antiangiogenic agents, arsenic trioxide, antisense oligonucleotides, anti-bone resorption agents such as osteoprotegerin and farnesyl transferase inhibitors, which are currently at preclinical or early clinical phases of investigation.

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

Table I
Table II
Table III

Notes

  1. 1.

    The use of trade names is for product identification purposes only and does not imply endorsement.

References

  1. 1.

    Bergsagel D, Sprague CC, Austin C, et al. Evaluation of new chemotherapeutic agents in the treatment of multiple myeloma IV. L-Phenylalanine Mustard (NSC8806). Cancer Chemother Rep 1962; 21: 87–99

  2. 2.

    Alexanian R, Haut A, Khan AU, et al. Treatment for multiple myeloma: combination chemotherapy with different melphalan dose regimens. JAMA 1969; 208: 1680–5

  3. 3.

    Joshua DE, Snowdon L, Gibson J, et al. Multiple myeloma plateau phase revisited. Haem Rev Comm 1991; 5: 59–66

  4. 4.

    Gregory WM, Richards MA, Malpas JS. Combination chemotherapy versus melphalan and prednisolone in the treatment of multiple myeloma: an overview of published trials. J Clin Oncol 1992; 10: 334–42

  5. 5.

    Myeloma Trialists’ Collaborative Group. Combination chemotherapy versus melphalan plus prednisone as treatment for multiple myeloma: an overview of 6633 patients from 27 randomized trials. Myeloma Trialists’ Collaborative Group. J Clin Oncol 1998; 16: 3832–42

  6. 6.

    DeVita VT, Hellman S, Rosenberg SA. Cancer: principles and practice of oncology. 3rd ed. P iladelphia (PA): JB Lippincott Co, 1989

  7. 7.

    Knoben JE, Anderson PO. Handbook of clinical drug data. 6th ed. H milton (IL): Drug Intelligence Publications Inc., 1988

  8. 8.

    Badros A, Barlogie B, Siegel E, et al. Results of autologous stem cell transplant in multiple myeloma patients with renal failure. Br J Haematol 2001; 114: 822–9

  9. 9.

    MacLennan IC, Kelly K, Crockson RA, et al. Results of the MRC myelomatosis trials for patients entered since 1980. Hematol Oncol 1988; 6: 145–58

  10. 10.

    Palumbo A, Boccadoro M, Bruno B, et al. Cyclophosphamide (3.6 g/m2) therapy with G-CSF support for resistant myeloma. Haematologica 1994; 79: 513–8

  11. 11.

    MacLennan IC, Chapman C, Dunn J, et al. Combined chemotherapy with ABCM versus melphalan for treatment of myelomatosis: The Medical Research Council Working Party for Leukaemia in Adults. Lancet 1992; 339: 200–5

  12. 12.

    CaseJr DC, LeeIII DJ, Clarkson BD. Improved survival times in multiple myeloma treated with melphalan, prednisone, cyclophosphamide, vincristine and BCNU: M-2 protocol. Am J Med 1977; 63: 897–903

  13. 13.

    Salmon SE, Haut A, Bonnet JD, et al. Alternating combination chemotherapy and levamisole improves survival in multiple myeloma: a Southwest Oncology Group Study. J Clin Oncol 1983; 1: 453–61

  14. 14.

    Alexanian R, Barlogie B, Tucker S. VAD-based regimens as primary treatment for multiple myeloma. Am J Hematol 1990; 33: 86–9

  15. 15.

    Barlogie B, Jagannath S, Vesole DH, et al. Superiority of tandem autologous transplantation over standard therapy for previously untreated multiple myeloma. Blood 1997; 89: 789–93

  16. 16.

    Samson D, Gaminara E, Newland A, et al. Infusion of vincristine and doxorubicin with oral dexamethasone as first-line therapy for multiple myeloma. Lancet 1989; II: 882–5

  17. 17.

    Segeren CM, Sonneveld P, van der Holt B, et al. Vincristine, doxorubicin and dexamethasone (VAD) administered as rapid intravenous infusion for first-line treatment in untreated multiple myeloma. Br J Haematol 1999; 105: 127–30

  18. 18.

    Tsiara SN, Kapsali E, Christou L, et al. Administration of a modified chemotherapeutic regimen containing vincristine, liposomal doxorubicin and dexamethasone to multiple myeloma patients: preliminary data. Eur J Haematol 2000; 65: 118–22

  19. 19.

    Northfelt DW, Martin FJ, Working P, et al. Doxorubicin encapsulated in liposomes containing surface-bound polyethylene glycol: pharmacokinetics, tumor localization, and safety in patients with AIDS-related Kaposi’s sarcoma. J Clin Pharmacol 1996; 36: 55–63

  20. 20.

    Alexanian R, Dimopoulos MA, Delasalle K, et al. Primary dexamethasone treatment of multiple myeloma. Blood 1992; 80: 887–90

  21. 21.

    Gertz MA, Garton JP, Greipp PR, et al. A phase II study of high-dose methyl-prednisolone in refractory or relapsed multiple myeloma. Leukemia 1995; 9: 2115–8

  22. 22.

    Tiplady CW, Summerfield GP. Continuous low-dose dexamethasone in relapsed or refractory multiple myeloma. Br JHaematol 2000; 111: 381

  23. 23.

    Peest D, Blade J, Harousseau JL, et al. Cytokine therapy in multiple myeloma. Br J Haematol 1996; 94: 425–32

  24. 24.

    Cooper MR, Dear K, Mclntyre OR, et al. A randomized clinical trial comparing melphalan/prednisone with or without interferon alfa-2b in newly diagnosed patients with multiple myeloma: a Cancer and Leukemia Group B study. J Clin Oncol 1993; 11: 155–60

  25. 25.

    Osterborg A, Bjorkholm M, Bjoreman M, et al. Natural interferon-alpha in combination with melphalan/prednisone versus melphalan/prednisone in the treatment of multiple myeloma stages II and III: a randomized study from the Myeloma Group of Central Sweden. Blood 1993; 81: 1428–34

  26. 26.

    The Myeloma Trialists’ Collaborative Group. Interferon as therapy for multiple myeloma: an individual patient data overview of 24 randomized trials and 4012 patients. Br JHaematol 2001; 113: 1020–34

  27. 27.

    Bjorkstrand B. Alpha-interferon maintenance treatment is associated with improved survival after high-dose treatment and autologous stem cell transplantation in patients with multiple myeloma: a retrospective registry study from the European Group for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplant 2001; 27: 511–5

  28. 28.

    Joshua DE, Penny R, Matthews JP, et al. Australian Leukaemia Study Group myeloma II: a randomized trial of intensive combination chemotherapy with or without interferon in patients with myeloma. Br J Haematol 1997; 97: 38–45

  29. 29.

    Cunningham D, Powles R, Malpas J, et al. A randomized trial of maintenance interferon following high-dose chemotherapy in multiple myeloma: long-term follow-up results. Br J Haematol 1998; 102: 495–502

  30. 30.

    Drayson MT, Chapman CE, Dunn JA, et al. MRC trial of alpha2b-interferon maintenance therapy in first plateau phase of multiple myeloma. MRC Working Party on Leukaemia in Adults. Br J Haematol 1998; 101: 195–2020

  31. 31.

    Pehamberger H. Perspectives of pegylated interferon use in dermatological oncology. Recent Results Cancer Res 2002; 160: 158–64

  32. 32.

    Fermand JP, Levy Y, Gerota J, et al. Treatment of aggressive multiple myeloma by high-dose chemotherapy and total body irradiation followed by blood stem cells autologous graft. Blood 1989; 73: 20–3

  33. 33.

    Cunningham D, Paz-Ares L, Milan S, et al. High-dose melphalan and autologous bone marrow transplantation as consolidation in previously untreated myeloma. J Clin Oncol 1994; 12: 759–63

  34. 34.

    Bjorkstrand B, Ljungman P, Bird JM, et al. Autologous stemcell transplantation in multiple myeloma: results of the European Group for Bone Marrow Transplantation. Stem Cells 1995; 13Suppl. 2: 140–6

  35. 35.

    Goldschmidt H, Hegenbart U, Wallmeier M, et al. High-dose chemotherapy in multiple myeloma. Leukemia 1997; 11Suppl. 5: S27–31

  36. 36.

    Barlogie B, Jagannath S, Tricot G, et al. Advances in the treatment of multiple myeloma. Adv Intern Med 1998; 43: 279–320

  37. 37.

    San Miguel JF, Blade Creixenti J, Garcia-Sanz R. Treatment of multiple myeloma. Haematologica 1999; 84: 36–58

  38. 38.

    Lokhorst HM, Sonneveld P, Verdonck LF. Intensive treatment for multiple myeloma: where do we stand? Br J Haematol 1999; 106: 18–27

  39. 39.

    Corradini P, Voena C, Tarella C, et al. Molecular and clinical remissions in multiple myeloma: role of autologous and allogeneic transplantation of hemato-poietic cells. J Clin Oncol 1999; 17: 208–15

  40. 40.

    Majolino I, Corradini P, Scime R, et al. Allogeneic transplantation of unmanipulated peripheral blood stem cells in patients with multiple myeloma. Bone Marrow Transplant 1998; 22: 449–55

  41. 41.

    Tricot G, Tricot G, Barlogie B, et al. Poor prognosis in multiple myeloma is associated only with partial or complete deletions of chromosome 13 or abnormalities involving 11q and not with other karyotype abnormalities. Blood 1995; 86: 4250–6

  42. 42.

    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

  43. 43.

    Lenhoff S, Hjorth M, Holmberg E, et al. Impact on survival of high-dose therapy with autologous stem cell support in patients younger than 60 years with newly diagnosed multiple myeloma: a population-based study. Nordic Myeloma Study Group. Blood 2000; 95: 7–11

  44. 44.

    Palumbo A, Triolo S, Argentino C, et al. Dose-intensive melphalan with stem cell support (MEL100) is superior to standard treatment in elderly myeloma patients. Blood 1999; 94: 1248–53

  45. 45.

    Blade J, SanMiguel JF, Fontanillas M, et al. Survival of multiple myeloma patients who are potential candidates for early high-dose therapy intensification/ autotransplantation and who were conventionally treated. J Clin Oncol 1996; 14: 2167–73

  46. 46.

    Blade J, Sureda A, Ribera J, et al. High-dose therapy autotransplantation/ intensification vs continued conventional chemotherapy in multiple myeloma patients responding to initial treatment chemotherapy: results of a prospective randomized trial from the Spanish Cooperative Group PETHEMA [abstract]. Blood 2001; 98: 815a

  47. 47.

    Fermand JP, Ravaud P, Katsahian S, et al. High dose therapy (HDT) and autologous blood stem cell (ABSC) transplantation versus conventional treatment in multiple myeloma (MM): results of a randomized trial in 190 patients 55 to 65 years of age [abstract]. Blood 1999; 94Suppl. 1: 396a

  48. 48.

    Rajkumar SV, Fonseca R, Dispenzieri A, et al. Effect of complete response on outcome following autologous stem cell transplantation for myeloma. Bone Marrow Transplant 2000; 26: 979–83

  49. 49.

    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

  50. 50.

    Siegel DS, Desikan KR, Mehta J, et al. Age is not a prognostic variable with autotransplants for multiple myeloma. Blood 1999; 93: 51–4

  51. 51.

    Bjorkstrand B. European Group for Blood and Marrow Transplantation Registry studies in multiple myeloma. Semin Haematol 2001; 38: 219–25

  52. 52.

    Diagnosis and management of multiple myeloma. Br J Haematol 2001; 115: 522-40

  53. 53.

    Barlogie B, Jagannath S, Desikan KR, et al. Total therapy with tandem transplants for newly diagnosed multiple myeloma. Blood 1999; 93: 55–65

  54. 54.

    Vescio RA, Han EJ, Schiller GJ, et al. Quantitative comparison of multiple myeloma tumor contamination in bone marrow harvest and leukapheresis autografts. Bone Marrow Transplant 1996; 18: 103–10

  55. 55.

    Haas R, Witt B, Mohle R, et al. Sustained long-term hematopoiesis after my-eloablative therapy with peripheral blood progenitor cell support. Blood 1995; 85: 3754–61

  56. 56.

    Tricot G, Jagannath S, Vesole D, et al. Peripheral blood stem cell transplants for multiple myeloma: identification of favorable variables for rapid engraftment in 225 patients. Blood 1995; 85: 588–96

  57. 57.

    Tricot G, Gazitt Y, Leemhuis T, et al. Collection, tumor contamination, and engraftment kinetics of highly purified hematopoietic progenitor cells to support high dose therapy in multiple myeloma. Blood 1998; 91: 4489–95

  58. 58.

    Demuynck H, Delforge M, Verhoef G, et al. Comparative study of peripheral blood progenitor cell collection in patients with multiple myeloma after single-dose cyclophosphamide combined with rhGM-CSF or rhG-CSF. Br J Haematol 1995; 90: 384–92

  59. 59.

    Fitoussi O, Perreau V, Boiron JM, et al. A comparison of toxicity following two different doses of cyclophosphamide for mobilization of peripheral blood progenitor cells in 116 multiple myeloma patients. Bone Marrow Transplant 2001; 27: 837–42

  60. 60.

    Demirer T, Buckner CD, Gooley T, et al. Factors influencing collection of peripheral blood stem cells in patients with multiple myeloma. Bone Marrow Transplant 1996; 17: 937–41

  61. 61.

    Facon T, Harousseau JL, Maloisel F, et al. Stem cell factor in combination with filgrastim after chemotherapy improves peripheral blood progenitor cell yield and reduces apheresis requirements in multiple myeloma patients: a randomized, controlled trial. Blood 1999; 94: 1218–25

  62. 62.

    Holowiecki J, Wojciechowska M, Giebel S, et al. Ifosfamide, etoposide, epirubicine, and G-CSF: an effective mobilization regimen for PBSCT in heavily pretreated patients. Transplant Proc 2000; 32: 1412–5

  63. 63.

    Szczepek AJ, Seeberger K, Wizniak J, et al. A high frequency of circulating B cells share clonotypic Ig heavy-chain VDJ rearrangements with autologous bone marrow plasma cells in multiple myeloma, as measured by single-cell and in situ reverse transcriptase-polymerase chain reaction. Blood 1998; 92: 2844–55

  64. 64.

    Vescio RA, Hong CH, Cao J, et al. The hematopoietic stem cell antigen, CD34, is not expressed on the malignant cells in multiple myeloma. Blood 1994; 84: 3283–90

  65. 65.

    Berenson RJ, Bensinger WI, Kalamasz D. Positive selection of viable cell populations using avidin-biotin immunoadsorption. J Immunol Methods 1986; 91: 11–9

  66. 66.

    McNiece I, Briddell R, Stoney G, et al. Large-scale isolation of CD34+ cells using the Amgen cell selection device results in high levels of purity and recovery. J Hematother 1997; 6: 5–11

  67. 67.

    Cottier-Fox M, Cipolone K, Yu M, et al. Positive selection of CD34+ hematopoietic cells using an immunoaffinity column results in T cell-depletion equivalent to elutriation. Exp Hematol 1995; 23: 320–2

  68. 68.

    Vescio R, Schiller G, Stewart AK, et al. Multicenter phase III trial to evaluate CD34(+) selected versus unselected autologous peripheral blood progenitor cell transplantation in multiple myeloma. Blood 1999; 93: 1858–68

  69. 69.

    Morineau N, Tang XW, Moreau P, et al. Lack of benefit of CD34+ cell selected over non-selected peripheral blood stem cell transplantation in multiple myeloma: results of a single center study. Leukemia 2000; 14: 1815–20

  70. 70.

    Murray L, Chen B, Galy A, et al. Enrichment of human hematopoietic stem cell activity in the CD34+Thy-1+Lin− subpopulation from mobilized peripheral blood. Blood 1995; 85: 368–78

  71. 71.

    Michallet M, Philip T, Philip I, et al. Transplantation with selected autologous peripheral blood CD34+Thyl+ hematopoietic stem cells (HSCs) in multiple myeloma: impact of HSC dose on engraftment, safety, and immune reconstitution. Exp Hematol 2000; 28: 858–70

  72. 72.

    Anderson KC, Barut BA, Ritz J, et al. Monoclonal antibody-purged autologous bone marrow transplantation therapy for multiple myeloma. Blood 1991; 77: 712–20

  73. 73.

    Reece DE, Barnett MJ, Connors JM, et al. Treatment of multiple myeloma with intensive chemotherapy followed by autologous BMT using marrow purged with 4-hydroperoxycyclophosphamide. Bone Marrow Transplant 1993; 11: 139–46

  74. 74.

    Reece DE, Brockington DA, Phillips GL, et al. Prolonged survival after intensive therapy and purged ABMT in patients with multiple myeloma. Bone Marrow Transplant 2000; 26: 621–6

  75. 75.

    Stewart AK, Vescio R, Schiller G, et al. Purging of autologous peripheral-blood stem cells using CD34 selection does not improve overall or progression-free survival after high-dose chemotherapy for multiple myeloma: results of a multicenter randomized controlled trial. J Clin Oncol 2001; 19: 3771–9

  76. 76.

    McElwain TJ, Powles R. High-dose intravenous melphalan for plasma-cell leukemia and myeloma. Lancet 1983; II: 822–4

  77. 77.

    Moreau P, Milpied N, Mahe B, et al. Melphalan 220 mg/m2 followed by peripheral blood stem cell transplantation in 27 patients with advanced multiple myeloma. Bone Marrow Transplant 1999; 23: 1003–6

  78. 78.

    Moreau P, Facon T, Attal M, et al. Comparison of 200 mg/m(2) melphalan and 8 Gy total body irradiation plus 140 mg/m(2) melphalan as conditioning regimens for peripheral blood stem cell transplantation in patients with newly diagnosed multiple myeloma: final analysis of the Intergroupe Francophone du Myelome 9502 randomized trial. Blood 2002; 99: 731–5

  79. 79.

    Bensinger WI, Rowley SD, Demirer T, et al. High-dose therapy followed by autologous hematopoietic stem-cell infusion for patients with multiple myeloma. J Clin Oncol 1996; 14: 1447–56

  80. 80.

    Desikan KR, Tricot G, Dhodapkar M, et al. Melphalan plus total body irradiation (MEL-TBI) or cyclophosphamide (MEL-CY) as a conditioning regimen with second autotransplant in responding patients with myeloma is inferior compared to historical controls receiving tandem transplants with melphalan alone. Bone Marrow Transplant 2000; 25: 483–7

  81. 81.

    Lahuerta JJ, Martinez-Lopez J, Grande C, et al. Conditioning regimens in autologous stem cell transplantation for multiple myeloma: a comparative study of efficacy and toxicity from the Spanish Registry for Transplantation in Multiple Myeloma. Br J Haematol 2000; 109: 138–47

  82. 82.

    Desikan R, Barlogie B, Sawyer J, 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: 4008–10

  83. 83.

    Attal M, Harousseau JL, Facon T, et al. Single vs double transplantation in myeloma: a prospective randomized trial of the Intergroupe Francophone de Myelome (IFM) [abstract]. Blood 2000; 96: 557a

  84. 84.

    Attal M, Harousseau JL. Randomized trial experience of the Intergroupe Francophone du Myelome. Semin Hematol 2001; 38: 226–30

  85. 85.

    Attal M, Harousseau JL, Facon T, et al. Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med 2001; 349: 2495–502

  86. 86.

    Gahrton G, Bjorkstrand B. Progress in haematopoietic stem cell transplantation for multiple myeloma. J Intern Med 2000; 248: 185–201

  87. 87.

    Joshua DE, MacCallum S, Gibson J. Role of alpha interferon in multiple myeloma. Blood Rev 1997; 11: 191–200

  88. 88.

    Gahrton G. Allogeneic bone marrow transplantation in multiple myeloma. Br J Haematol 1996; 92: 251–4

  89. 89.

    Bensinger WI, Buckner CD, Anasetti C, et al. Allogeneic marrow transplantation for multiple myeloma: an analysis of risk factors on outcome. Blood 1996; 88: 2787–93

  90. 90.

    Lokhorst HM, Sonneveld P, Cornelissen JJ, et al. Induction therapy with vincristine, adriamycin, dexamethasone (VAD) and intermediate-dose melphalan (IDM) followed by autologous or allogeneic stem cell transplantation in newly diagnosed multiple myeloma. Bone Marrow Transplant 1999; 23: 317–22

  91. 91.

    Blade J, Esteve J. Treatment approaches for relapsing and refractory multiple myeloma. Acta Oncol 2000; 39: 843–7

  92. 92.

    Alyea E, Weiler E, Schlossman R, et al. T-cell-depleted allogeneic bone marrow transplantation followed by donor lymphocyte infusion in patients with multiple myeloma: induction of graft-versus-myeloma effect. Blood 2001; 98: 934–9

  93. 93.

    Byrne JL, Carter GI, Bienz N, et al. Adjuvant alpha-interferon improves complete remission rates following allogeneic transplantation for multiple myeloma. Bone Marrow Transplant 1998; 22: 639–43

  94. 94.

    Gahrton G, Tura S, Ljungman P, et al. Prognostic factors in allogeneic bone marrow transplantation for multiple myeloma. J Clin Oncol 1995; 13: 1312–22

  95. 95.

    Alyea EP, Soiffer RJ, Canning C, et al. Toxicity and efficacy of defined doses of CD4(+) donor lymphocytes for treatment of relapse after allogeneic bone marrow transplant. Blood 1998; 91: 3671–80

  96. 96.

    Lokhorst HM, Liebowitz D. Adoptive T-cell therapy. Semin Hematol 1999; 36: 26–9

  97. 97.

    Lokhorst HM, Schattenberg A, Cornelissen JJ, et al. Donor leukocyte infusions are effective in relapsed multiple myeloma after allogeneic bone marrow transplantation. Blood 1997; 90: 4206–11

  98. 98.

    Salama M, Nevill T, Marcellus D, et al. Donor leukocyte infusions for multiple myeloma. Bone Marrow Transplant 2000; 26: 1179–84

  99. 99.

    Kroger N, Kruger W, Renges H, et al. Donor lymphocyte infusion enhances remission status in patients with persistent disease after allografting for multiple myeloma. Br J Haematol 2001; 112: 421–3

  100. 100.

    Badros A, Barlogie B, Siegel E, et al. Improved outcome of allogeneic transplantation in high-risk multiple myeloma patients after nonmyeloablative conditioning. J Clin Oncol 2002; 20: 1295–303

  101. 101.

    Badros A, Barlogie B, Morris C, et al. High response rate in refractory and poor-risk multiple myeloma after allotransplantation using a nonmyeloablative conditioning regimen and donor lymphocyte infusions. Blood 2001; 97: 2574–9

  102. 102.

    Lokhorst HM, Schattenberg A, Cornelissen JJ, et al. Donor lymphocyte infusions for relapsed multiple myeloma after allogeneic stem-cell transplantation: predictive factors for response and long-term outcome. J Clin Oncol 2000; 18: 3031–7

  103. 103.

    MacKinnon S. Who may benefit from donor leucocyte infusions after allogeneic stem cell transplantation? Br J Haematol 2000; 110: 12–7

  104. 104.

    Gahrton G, Svensson H, Bjorkstrand B, et al. Syngeneic transplantation in multiple myeloma: a case-matched comparison with autologous and allogeneic transplantation. European Group for Blood and Marrow Transplantation. Bone Marrow Transplant 1999; 24: 741–5

  105. 105.

    Bensinger WI, Demirer T, Buckner CD, et al. Syngeneic marrow transplantation in patients with multiple myeloma. Bone Marrow Transplant 1996; 18: 527–31

  106. 106.

    Alexanian R, Barlogie B, Dixon D. High-dose glucocorticoid treatment of resistant myeloma. Ann Intern Med 1986; 105: 8–11

  107. 107.

    Alexanian R, Dimopoulos MA, Hester J, et al. Early myeloablative therapy for multiple myeloma. Blood 1994; 84: 4278–82

  108. 108.

    Barlogie B, Zangari M, Spencer T, et al. Thalidomide in the management of multiple myeloma. Semin Hematol 2001; 38: 250–9

  109. 109.

    Belch A, Shelley W, Bergsagel D, et al. A randomized trial of maintenance versus no maintenance melphalan and prednisone in responding multiple myeloma patients. Br J Cancer 1988; 57: 94–9

  110. 110.

    Buzaid AC, Durie BG. Management of refractory myeloma: a review. J Clin Oncol 1988; 6: 889–905

  111. 111.

    Barlogie B, Smith L, Alexanian R. Effective treatment of advanced multiple myeloma refractory to alkylating agents. N Engl J Med 1984; 310: 1353–6

  112. 112.

    Berman E, McBride M. Comparative cellular pharmacology of daunorubicin and idarubicin in human multidrug-resistant leukemia cells. Blood 1992; 79: 3267–73

  113. 113.

    Parameswaran R, Giles C, Boots M, et al. CCNU (lomustine), idarubicin and dexamethasone(CIDEX): an effective oral regimen for the treatment of refractory or relapsed myeloma. Br J Haematol 2000; 109: 571–5

  114. 114.

    Barlogie B, Desikan R, Eddlemon 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: 492–4

  115. 115.

    Juliusson G, Celsing F, Turesson I, et al. Frequent good partial remissions from thalidomide including best response ever in patients with advanced refractory and relapsed myeloma. Br J Haematol 2000; 109: 89–96

  116. 116.

    Singhal S, Mehta J, Desikan R, et al. Antitumor activity of thalidomide in refractory multiple myeloma [published erratum appears in N Engl J Med 2000; 342: 364]. N Engl J Med 1999; 341: 1565–71

  117. 117.

    Alexanian R, Barlogie B, Gutterman J. Alpha-interferon combination therapy of resistant myeloma. Am J Clin Oncol 1991; 14: 188–92

  118. 118.

    Mansi JL, Cunningham D, Viner C, et al. Repeat administration of high dose melphalan in relapsed myeloma. Br J Cancer 1993; 68: 983–7

  119. 119.

    Tricot G, Jagannath S, Vesole DH, et al. Relapse of multiple myeloma after autologous transplantation: survival after salvage therapy. Bone Marrow Transplant 1995; 16:7–11

  120. 120.

    Mehta J, Tricot G, Jagannath S, et al. Salvage autologous or allogeneic transplantation for multiple myeloma refractory to or relapsing after a first-line autograft? Bone Marrow Transplant 1998; 21: 887–92

  121. 121.

    Vesole DH, Tricot G, Jagannath S, et al. Autotransplants in multiple myeloma: what have we learned? Blood 1996; 88: 838–47

  122. 122.

    Raje N, Anderson K. Thalidomide: a revival story. N Engl J Med 1999; 341: 1606–9

  123. 123.

    Munshi NC, Wilson C. Increased bone marrow microvessel density in newly diagnosed multiple myeloma carries a poor prognosis. Semin Oncol 2001; 28: 565–9

  124. 124.

    Vacca A, Ribatti D, Presta M, et al. Bone marrow neovascularization, plasma cell angiogenic potential, and matrix metalloproteinase-2 secretion parallel progression of human multiple myeloma. Blood 1999; 93: 3064–73

  125. 125.

    Rajkumar SV, Fonseca R, Dispenzieri A, et al. Thalidomide in the treatment of relapsed multiple myeloma. Mayo Clin Proc 2000; 75: 897–901

  126. 126.

    Kneller A, Raanani P, Hardan I, et al. Therapy with thalidomide in refractory multiple myeloma patients: the revival of an old drug. Br JHaematol 2000; 108: 391–3

  127. 127.

    Rajkumar SV. Thalidomide in multiple myeloma. Oncology 2000; 14(12 Suppl. 13): 11–6

  128. 128.

    Zangari M, Anaissie E, Barlogie B, et al. Increased risk of deep-vein thrombosis in patients with multiple myeloma receiving thalidomide and chemotherapy. Blood 2001; 98: 1614–5

  129. 129.

    Durie BGM, Stepan DE. Low dose thalidomide: alone and in combination. Proceedings of the VIIIth International Myeloma Workshop; 2001 May 4–8; Banff (AB), 11-2

  130. 130.

    Blade J, Perales M, Rosinol L, et al. Thalidomide in multiple myeloma: lack of response of soft-tissue plasmacytomas. Br J Haematol 2001; 113: 422–4

  131. 131.

    Hughes DE, Wright KR, Uy HL, et al. Bisphosphonates promote apoptosis in murine osteoclasts in vitro and in vivo. J Bone Miner Res 1995; 10: 1478–87

  132. 132.

    Shipman CM, Rogers MJ, Vanderkerken K, et al. Bisphosphonates: mechanisms of action in multiple myeloma. Acta Oncol 2000; 39: 829–35

  133. 133.

    Teronen O, Laitinen M, Salo T, et al. Inhibition of matrix metalloproteinases by bisphosphonates may in part explain their effects in the treatment of multiple myeloma. Blood 2000; 96: 4006–7

  134. 134.

    Aparicio A, Gardner A, Tu Y, et al. In vitro cytoreductive effects on multiple myeloma cells induced by bisphosphonates. Leukemia 1998; 12: 220–9

  135. 135.

    Shipman CM, Rogers MJ, Apperley JF, et al. Bisphosphonates induce apoptosis in human myeloma cell lines: a novel anti-tumour activity. Br J Haematol 1997; 98: 665–72

  136. 136.

    Dhodapkar MV, Singh J, Mehta J, et al. Anti-myeloma activity of pamidronate in vivo. Br J Haematol 1998; 103: 530–2

  137. 137.

    Lahtinen R, Laakso M, Palva I, et al. Randomised, placebo-controlled multicentre trial of clodronate in multiple myeloma. Finnish Leukaemia Group [published erratum in Lancet 1992; 340:1420]. Lancet 1992; 340: 1049–52

  138. 138.

    McCloskey EV, MacLennan IC, Drayson MT, et al. A randomized trial of the effect of clodronate on skeletal morbidity in multiple myeloma. MRC Working Party on Leukaemia in Adults. Br J Haematol 1998; 100: 317–25

  139. 139.

    Berenson JR, Lichtenstein A, Porter L, et al. Efficacy of pamidronate in reducing skeletal events in patients with advanced multiple myeloma. Myeloma Aredia Study Group. N Engl J Med 1996; 334: 488–93

  140. 140.

    Berenson JR, Lichtenstein A, Porter L, et al. Long-term pamidronate treatment of advanced multiple myeloma patients reduces skeletal events. Myeloma Aredia Study Group. J Clin Oncol 1998; 16: 593–602

  141. 141.

    Major P, Lortholary A, Hon J, et al. Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled clinical trials. J Clin Oncol 2001; 19: 558–67

  142. 142.

    Berenson JR, Rosen LS, Howell A, et al. Zoledronic acid reduces skeletal-related events in patients with osteolytic mEetastases [published erratum in Cancer 2001 15; 91: 1956]. Cancer 2001; 91: 1191–200

  143. 143.

    Rosen LS, Gordon D, Antonio BS, et al. Zoledronic acid versus pamidronate in the treatment of skeletal metastases in patients with breast cancer or osteolytic lesions of multiple myeloma: a phase III, double-blind, comparative trial. Cancer J 2001; 7: 377–87

  144. 144.

    Bergenbrant S, Osterborg A, Holm G, et al. Anti-idiotypic antibodies in patients with monoclonal gammopathies: relation to the tumour load. Br J Haematol 1991; 78: 66–70

  145. 145.

    Yi Q, Eriksson I, He W, et al. Idiotype-specific T lymphocytes in monoclonal gammopathies: evidence for the presence of CD4+ and CD8+ subsets. Br J Haematol 1997; 96: 338–45

  146. 146.

    Stevenson FK, Anderson KC. Preparing the ground for vaccination against multiple myeloma. Immunol Today 2000; 21: 170–1

  147. 147.

    Szea DM, Brown RD, Yang S. Prediction of high affinity class I-restricted multiple myeloma idiotype peptide epitopes. Leuk Lymphoma 2003; 44: 1557–68

  148. 148.

    Massaia M. Idiotype vaccination of myeloma patients after chemotherapy. Acta Oncol 2000; 39: 807–8

  149. 149.

    Trojan A, Schultze JL, Witzens M, et al. Immunoglobulin framework-derived peptides function as cytotoxic T-cell epitopes commonly expressed in B-cell malignancies. Nat Med 2000; 6: 667–72

  150. 150.

    Bergenbrant S, Yi Q, Osterborg A, et al. Modulation of anti-idiotypic immune response by immunization with the autologous M-component protein in multiple myeloma patients. Br J Haematol 1996; 92: 840–6

  151. 151.

    Osterborg A, Yi Q, Henriksson L, et al. Idiotype immunization combined with granulocyte-macrophage colony-stimulating factor in myeloma patients induced type I, major histocompatibility complex-restricted, CD8- and CD4-specific T-cell responses. Blood 1998; 91: 2459–66

  152. 152.

    Neelapu SS, Baskar S, Kwak LW. Detection of keyhole limpet hemocyanin (KLH)-specific immune responses by intracellular cytokine assay in patients vaccinated with idiotype-KLH vaccine. J Cancer Res Clin Oncol 2001; 127: R14–9

  153. 153.

    Titzer S, Christensen O, Manzke O, et al. Vaccination of multiple myeloma patients with idiotype-pulsed dendritic cells: immunological and clinical aspects. Br J Haematol 2000; 108: 805–16

  154. 154.

    Reichardt VL, Okada CY, Liso A, et al. Idiotype vaccination using dendritic cells after autologous peripheral blood stem cell transplantation for multiple myeloma: a feasibility study. Blood 1999; 93: 2411–9

  155. 155.

    Cull G, Durrant L, Stainer C, et al. Generation of anti-idiotype immune responses following vaccination with idiotype-protein pulsed dendritic cells in myeloma. Br J Haematol 1999; 107: 648–55

  156. 156.

    Kwak LW, Taub DD, Duffey PL, et al. Transfer of myeloma idiotype-specific immunity from an actively immunised marrow donor. Lancet 1995; 345: 1016–20

  157. 157.

    SanMiguel JF, Gonzalez M, Gascon A, et al. Lymphoid subsets and prognostic factors in multiple myeloma. Cooperative Group for the Study of Monoclonal Gammopathies. Br J Haematol 1992; 80: 305–9

  158. 158.

    Frassanito MA, Silvestris F, Cafforio P, et al. CD8+/CD57 cells and apoptosis suppress T-cell functions in multiple myeloma. Br J Haematol 1998; 100: 469–77

  159. 159.

    Steinman RM. The dendritic cell system and its role in immunogenicity. Annu Rev Immunol 1991; 9: 271–96

  160. 160.

    Strunk D, Rappersberger K, Egger C, et al. Generation of human dendritic cells/ Langerhans cells from circulating CD34+ hematopoietic progenitor cells. Blood 1996; 87: 1292–302

  161. 161.

    Romani N, Gruner S, Brang D, et al. Proliferating dendritic cell progenitors in human blood. J Exp Med 1994; 180: 83–93

  162. 162.

    Grabbe S, Beissert S, Schwarz T, et al. Dendritic cells as initiators of tumor immune responses: a possible strategy for tumor immunotherapy? Immunol Today 1995; 16: 117–21

  163. 163.

    Li J, Holmes LM, Franek KJ, et al. Purified hybrid cells from dendritic cell and tumor cell fusions are superior activators of antitumor immunity. Cancer Immunol Immunother 2001; 50: 456–62

  164. 164.

    Brown RD, Pope B, Murray A, et al. Dendritic cells from patients with myeloma are numerically normal but functionally defective as they fail to up-regulate CD80 (B7-1) expression after huCD40LT stimulation because of inhibition by transforming growth factor-1 and interleukin-10. Blood 2001; 98: 2292–8

  165. 165.

    Davies FE, Anderson KC. Novel therapeutic targets in multiple myeloma. Eur J Haematol 2000; 64: 359–67

  166. 166.

    Hart DN. Dendritic cells and their emerging clinical applications. Pathology 2001; 33: 479–92

  167. 167.

    King CA, Speilerberg MB, Zhu D, et al. DNA vaccines with single-chain Fv fused to fragment C of tetanus toxin induce protective immunity against lymphoma and myeloma. Nat Med 1998; 4: 1281–6

  168. 168.

    Stevenson FK, Link Jr CJ, Traynor A, et al. DNA vaccination against multiple myeloma. Semin Hematol 1999; 36: 38–42

  169. 169.

    Kawano M, Hirano T, Matsuda T, et al. Autocrine generation and requirement of BSF-2/IL-6 for human multiple myelomas. Nature 1988; 332: 83–5

  170. 170.

    Klein B, Zhang XG, Jourdan M, et al. Paracrine rather than autocrine regulation of myeloma-cell growth and differentiation by interleukin-6. Blood 1989; 73: 517–6

  171. 171.

    Bataille R, Barlogie B, Lu ZY, et al. Biologic effects of anti-interleukin-6 murine monoclonal antibody in advanced multiple myeloma. Blood 1995; 86: 685–91

  172. 172.

    Klein B, Wijdenes J, Zhang XG, et al. Murine anti-interleukin-6 monoclonal antibody therapy for a patient with plasma cell leukemia. Blood 1991; 78: 1198–204

  173. 173.

    van Zaanen HC, Lokhorst HM, Aarden LA, et al. Chimaeric anti-interleukin 6 monoclonal antibodies in the treatment of advanced multiple myeloma: a phase I dose-escalating study. Br J Haematol 1998; 102: 783–90

  174. 174.

    Suzuki H, Yasukawa K, Saito T, et al. Anti-human interleukin-6 receptor antibody inhibits human myeloma growth in vivo. Eur J Immunol 1992; 22: 1989–93

  175. 175.

    Treon SP, Shima Y, Grossbard ML, et al. Treatment of multiple myeloma by antibody mediated immunotherapy and induction of myeloma selective antigens. Ann Oncol 2000; 11: 107–11

  176. 176.

    Stevenson FK, Bell AJ, Cusack R, et al. Preliminary studies for an immunother-apeutic approach to the treatment of human myeloma using chimeric anti-CD38 antibody. Blood 1991; 77: 1071–9

  177. 177.

    Vooijs WC, Schuurman HJ, Bast EJ, et al. Evaluation of CD38 as target for immunotherapy in multiple myeloma. Blood 1995; 85: 2282–4

  178. 178.

    Post J, Vooijs WC, Bast BJ, et al. Efficacy of an anti-CD138 immunotoxin and doxorubicin on drug-resistant and drug-sensitive myeloma cells. Int J Cancer 1999; 83: 571–6

  179. 179.

    Supiot S, Faivre-Chauvet A, Couturier O, et al. Comparison of the biologic effects of MA5 and B-B4 monoclonal antibody labeled with iodine-131 and bismuth-213 on multiple myeloma. Cancer 2002; 94: 1202–9

  180. 180.

    Ozaki S, Kosaka M, Wakatsuki S,etal. Immunotherapy of multiple myeloma with a monoclonal antibody directed against a plasma cell-specific antigen, HM1.24. Blood 1997; 90: 3179–86

  181. 181.

    Treon SP, Mollick JA, Urashima M, et al. Muc-1 core protein is expressed on multiple myeloma cells and is induced by dexamethasone. Blood 1999; 93: 1287–98

  182. 182.

    King RW, Deshaies RJ, Peters JM, et al. How proteolysis drives the cell cycle. Science 1996; 274: 1652–9

  183. 183.

    LeBlanc R, Catley L, Hideshima T, et al. Proteasome inhibitor PS-341 inhibits multiple myeloma cell growth in a murine model [abstract]. Blood 2001; 99: 774a

  184. 184.

    Hideshima T, Richardson P, Chauhan D, et al. The proteasome inhibitor PS-341 inhibits growth, induces apoptosis, and overcomes drug resistance in human multiple myeloma cells. Cancer Res 2001; 61: 3071–6

  185. 185.

    Berenson JR, Ma HM, Vescio R. The role of nuclear factor-kappaB in the biology and treatment of multiple myeloma. Semin Oncol 2001; 28: 626–33

  186. 186.

    Ma HM, Parker KM, Manyak S, et al. Proteasome inhibitor PS-341 markedly enhances sensitivity of multiple myeloma cells to chemotherapeutic agents and overcomes resistance through inhibition of the NF-kB pathway [abstract]. Blood 2001; 99: 473a

  187. 187.

    Hideshima T, Chauhan D, Podar K, et al. Novel therapies targeting the myeloma cell and its bone marrow microenvironment. Semin Oncol 2001; 28: 607–12

  188. 188.

    Richardson PG, Berenson J, Irwin D, et al. Phase II study of PS-341, a novel proteasome inhibitor, alone or in combination with dexamethasome in patients with multiple myeloma who have relapsed following front-line therapy and are refractory to their most recent therapy [abstract]. Blood 2001; 99: 774a

  189. 189.

    Anderson KC. Targeted therapy for multiple myeloma. Semin Hematol 2001; 38: 286–94

  190. 190.

    Mitsiades N, Mitsiades CS, Poulaki V, et al. Apoptotic signalling by immunomodulatory thalidomide analogs (IMiDs) in human multiple myeloma cells: therapeutic implications [abstract]. Blood 2001; 98: 775a

  191. 191.

    Davies FE, Raje N, Hideshima T, et al. Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma. Blood 2001; 98: 210–6

  192. 192.

    Hideshima T, Chauhan D, Shima Y, et al. Thalidomide and its analogs overcome drug resistance of human multiple myeloma cells to conventional therapy. Blood 2000; 96: 2943–50

  193. 193.

    Richardson PG, Schlossman RL, Hideshima T, et al. A Phase I study of CC5013, an immunomodultory thalidomide derivative, in patients with relapsed and refractory multiple myeloma [abstract]. Blood 2001; 98: 774a

  194. 194.

    Albitar M, Smolich B, Cherrington J, et al. Effects of SU5416 on angiogenic factors, proliferation and apoptosis in patients with hematological malignancies [abstract]. Blood 2001; 98: 110a

  195. 195.

    Zangari M, Stopeck AT, Karp J, et al. Phase II study of SU5416 in patients with multiple myeloma [abstract]. Blood 2001; 98: 164a

  196. 196.

    Jagganath S, Champagne P, Hariton C, et al. Neovastat (AE-941) in multiple myeloma [abstract]. Blood 2001; 98: 309b

  197. 197.

    Anderson KC, Boise LH, Louie R, et al. Arsenic trioxide in multiple myeloma: rationale and future directions. Cancer J 2002; 8: 12–5

  198. 198.

    Hayashi T, Hideshima T, Akiyama M, et al. Arsenic trioxide inhibits growth of human multiple myeloma cells in the bone marrow microenvironment [abstract]. Blood 2001; 99: 375a

  199. 199.

    Grad JM, Bahlis NJ, Reis I, et al. Ascorbic acid enhances arsenic tri oxide-induced cytotoxicity in multiple myeloma cells. Blood 2001; 98: 805–13

  200. 200.

    Hideshima T, Chauhan D, Castro A, et al. NF-kB as therapeutic target in multiple myeloma [abstract]. Blood 2001; 98: 375a

  201. 201.

    Gazitt Y, Dover D, Liu Q. The mechanism of arsenic trioxide (ATO: Trisenox)-induced apoptosis: independence of bcl-2; involvement of G2/M cell cycle arrest and upregulation of surface TRAIL receptors [abstract]. Blood 2001; 98: 159a

  202. 202.

    Bahlis NJ, Jordan-McMurry I, Grad JM, et al. Phase I results from a Phase I/II study of arsenic trioxide (AS2O3) and ascorbic acid (AA) in relapsed and chemorefractory multiple myeloma [abstract]. Blood 2001; 98: 375a

  203. 203.

    Hussein MA, Mason J, Ravandi F, et al. A Phase II clinical study of arsenic trioxide (ATO) in patients with relapsed or refractory multiple myeloma: a preliminary report [abstract]. Blood 2001; 98: 378a

  204. 204.

    Munshi NC. Arsenic trioxide: an emerging therapy for multiple myeloma. Oncologist 2001; 6: 17–21

  205. 205.

    Evens A, Prachand S, Li Y, et al. In vitro potentiation of arsenic trioxide cytotoxicity through novel combination therapy with imexon fo multiple myeloma [abstract]. Blood 2001; 98: 375a

  206. 206.

    Gartenhaus RB, Prachand SN, Paniaqua M, et al. Arsenic trioxide cytotoxicity in steroid and chemotherapy-resistant myeloma cell lines: enhancement of apoptosis by manipulation of cellular redox state. Clin Cancer Res 2002; 8: 566–72

  207. 207.

    Hallek M, Bergsagel PL, Anderson KC. Multiple myeloma: increasing evidence for a multistep transformation process. Blood 1998; 91: 3–21

  208. 208.

    Derenne S, Monia B, Dean NM, et al. Antisense strategy provides evidence that mcl-1 is the essential survival protein and a major therapeutic target in myeloma cells [abstract]. Blood 2001; 98: 773a

  209. 209.

    Gazitt Y, Liu Q, Vesole D. Bcl-2 antisense oligonucleotides (ASO) enhances apoptosis and cytotoxicity in drug-resistant myeloma cells [abstract]. Blood 2001; 98: 641a

  210. 210.

    Le Gouill S, Pellat-Deceunynck C, Bataille R, et al. Farnesyl transferase inhibitor (Rl 15777) induced major apoptosis in human myeloma cells by targeting both JAK/SAR and ERK pathways [abstract]. Proceedings of the 93rd Annual Meeting of the American Association for Cancer Research; 2002 Apr 6–10; S n Francisco (CA). Proc AACR 2002; 43: 601

  211. 211.

    Alsina M, Overton R, Belle N, et al.Franesyl transferase inhibitor FTI-R115777 is well tolerated, induces stabilization of disease and inhibits farnesylation and oncogenic/ tumor survival pathways in patients with advanced multiple myeloma [abstract]. Proceedings of the 93rd Annual Meeting of the American Association for Cancer Research; 2002 Apr 6–10; S n Francisco (CA). Proc AACR 2002; 43: 1000

  212. 212.

    Callander NS, Roodman GD. Myeloma bone disease. Semin Hematol 2001; 38: 276–85

  213. 213.

    Hofbauer LC, Neubauer A, Heufelder AE. Receptor activator of nuclear factor-kappaB ligand and osteoprotegerin: potential implications for the pathogenesis and treatment of malignant bone diseases. Cancer 2001; 92: 460–70

  214. 214.

    Giuliani N, Bataille R, Mancini C, et al. Myeloma cells induce imbalance in the osteoprotegerin/osteoprotegerin ligand system in the human bone marrow environment. Blood 2001; 98: 3527–33

  215. 215.

    Croucher PI, Shipman CM, Lippitt J, et al. Osteoprotegerin inhibits the development of osteolytic bone disease in multiple myeloma. Blood 2001; 98: 3534–40

  216. 216.

    Seidel C, Hjertner O, Abildgaard N, et al. Serum osteoprotegerin levels are reduced in patients with multiple myeloma with lytic bone disease. Blood 2001; 98: 2269–71

  217. 217.

    Borset M, Standal T, Hjertner O, et al. Binding, internalization and degradation of osteoprotegerin in human myeloma cells [abstract]. Blood 2001; 98: 636a

  218. 218.

    Plesner T, Boissy P, Dartell M, et al. Myeloma cells express and release Rank-ligand that promotes the generation of osteoclast-like cells [abstract]. Blood 2001; 98: 302b

  219. 219.

    Griepp P, Facon T, Williams CD, et al. A single subcutaneous dose of an osteoprotegerin (OPG) construct (AMGN-0007) causes a profound and sustained decrease of bone resorption comparable to standard intravenous bisphos-phonate in patients with multiple myeloma [abstract]. Blood 2001; 98: 775a

  220. 220.

    Sonneveld P, Durie BG, Lokhorst HM, et al. Modulation of multidrug-resistant multiple myeloma by cyclosporin. The Leukaemia Group of the EORTC and the HOVON. Lancet 1992; 340: 255–9

  221. 221.

    Kraut EH, Crowley JJ, Wade JL, et al. Evaluation of topotecan in resistant and relapsing multiple myeloma: a Southwest Oncology Group study. J Clin Oncol 1998; 16:589–92

  222. 222.

    Durie BGM, Villarete L, Favard A, et al. Clarithromycin (Biaxin) as primary treatment for myeloma [abstract]. Blood 1997; 90Suppl. 1: 579a

  223. 223.

    Stewart AK, Trudel S, Al-Berouti BM, et al. Lack of response to short-term use of clarithromycin (BIAXIN) in multiple myeloma [letter]. Blood 1999; 93: 4441

  224. 224.

    Moreau P, Huynh A, Facon T, et al. Lack of efficacy of clarithromycin in advanced multiple myeloma. Intergroupe Francais du Myelome (IFM). Leukemia 1999; 13: 490–1

  225. 225.

    Shrieve DC. The role of radiotherapy. In: Mehta J, Singhai S. Myeloma. L ndon: Martin Dunitz Ltd, 2002: 367–82

  226. 226.

    Hu K, Yahalom J. Radiotherapy in the management of plasma cell tumors. Oncology 2000; 14: 101–8

  227. 227.

    Leigh BR, Kurtts TA, Mack CF, et al. Radiation therapy for the palliation of multiple myeloma. Int J Radiat Oncol Biol Phys 1993; 25: 801–4

  228. 228.

    Salmon SE, Tesh D, Crowley J, et al. Chemotherapy is superior to sequential hemibody irradiation for remission consolidation in multiple myeloma: a Southwest Oncology Group study. J Clin Oncol 1990; 8: 1575–84

Download references

Acknowledgements

We acknowledge the support of the University of Sydney Cancer Research Fund and the Anthony Rothe Memorial Trust. The authors have no conflicts of interest that are directly relevant to the content of this review.

Author information

Correspondence to Professor Douglas E. Joshua.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Ho, P.J., Gibson, J. & Joshua, D.E. Treatment of Multiple Myeloma. Am J Cancer 3, 47–66 (2004). https://doi.org/10.2165/00024669-200403010-00005

Download citation

Keywords

  • Vascular Endothelial Growth Factor
  • Overall Survival
  • Multiple Myeloma
  • Thalidomide
  • Pamidronate