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Therapeutic Options in the Treatment of Multiple Myeloma

Pharmacoeconomic and Quality-of-Life Considerations

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Abstract

A review of current treatment options in multiple myeloma is presented, including data on health-related quality of life and pharmacoeconomics. For induction chemotherapy, no combination of cytostatic drugs has been shown to be consistently superior to the simple cyclic oral treatment with melphalan and prednisone that has been available for 30 years. The total resource consumption and direct costs per patient treated with melphalan and prednisone is approximately $US10 000 (1995 values). As median survival is prolonged from less than a year in untreated patients to 30 to 36 months, this treatment must be considered cost effective. Interferon-a has a modest effect on progression-free and overall survival when added to chemotherapy regimens.However, the high cost and toxicity of this drug results in an unfavourable cost-utility ratio, estimated to be between $US50 000 to $US100 000 per quality-adjusted life-year gained.

Clinical trials suggest that high dose chemotherapy followed by autologous stemcell support administered to patientswho have achieved disease stabilisation or objective response to conventional induction chemotherapy, prolongs median survival by about 1.5 years. Preliminary cost-utility analyses suggest a cost per life-year gained of $US30 000 to $US40 000. Further potential improvements of this therapeutic modality are under way.

Several bisphosphonates have been tested for the ability to prevent the skeletal complications of multiple myeloma. Monthly infusions of pamidronate have been shown in 1 randomised trial to significantly reduce the rate of skeletal complications. Unfortunately, the rapid and widespread acceptance of this therapy seems to preclude further prospective, placebo-controlled trials with cost-utility evaluation.

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References

  1. Kyle RA, Bayrd ED. The monoclonal gammopathies: multiple myeloma and related cell disorders. Springfield (IL): Charles C. Thomas, 1976

    Google Scholar 

  2. Wisløff F, Eika S, Hippe E, et al. Measurement of health-related quality of life in multiple myeloma. Br J Haematol 1996; 92: 604–13

    Article  PubMed  Google Scholar 

  3. Turesson I, Zettervall O, Cuzick J, et al. Comparison of trends in the incidence of multiple myeloma in Malmö, Sweden and other countries. N Engl J Med 1984; 310: 421–4

    Article  PubMed  CAS  Google Scholar 

  4. Wisløff F, Andersen P, Andersson TR, et al. Has the incidence of multiple myeloma in old age been underestimated? Eur J Haematol 1991; 47: 333–7

    Article  PubMed  Google Scholar 

  5. The Myeloma Trialists’ Collaborative Group. Combination chemotherapy versus melphalan plus prednisone as treatment for multiple myeloma: an overview of 6,633 patients from 27 randomized trials. J Clin Oncol 1998; 16: 3832–42

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  7. Oken MM, Harrington DP, Abramson N, et al. Comparison of melphalan and prednisone with vincristine, carmustine, melphalan, cyclophosphamide and prednisone in the treatment of multiple myeloma. Cancer 1997; 79: 1561–7

    Article  PubMed  CAS  Google Scholar 

  8. Durie GM, Dixon DO, Carter S, et al. Improved survival duration with combination chemotherapy induction for multiple myeloma: a Southwest Oncology Study Group study. J Clin Oncol 1986; 4: 1227–37

    PubMed  CAS  Google Scholar 

  9. MacLennan ICM, Chapman C, Dunn J, et al. Combined chemotherapy with ABCM versus melphalan for the treatment of myelomatosis. Lancet 1992; 339: 200–5

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  11. 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; 8: 453–61

    Google Scholar 

  12. Österborg A, Åhre A, Björkholm M, et al. Alternating combination chemotherapy (VMCP/VBAP) is not superior to melphalan/prednisone in the treatment of multiple myeloma stage III: a randomized study from MGCS. Eur J Haematol 1989; 43: 54–62

    Article  PubMed  Google Scholar 

  13. Hjorth M, Hellquist L, Holmberg E, et al. Initial treatment in multiple myeloma: no advantage of multidrug chemotherapy over melphalan-prednisone. Br J Haematol 1990; 74: 185–91

    Article  PubMed  CAS  Google Scholar 

  14. Nord E, Wisløff F, Hjorth M, et al. Cost-utility analysis of melphalan plus prednisone with or without interferon- 2b in newly diagnosed multiple myeloma. Pharmacoeconomics 1997; 12: 89–103

    Article  PubMed  CAS  Google Scholar 

  15. 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

    Article  PubMed  CAS  Google Scholar 

  16. Osterborg A, Björkholm M, Björeman M, et al. Natural interferon-α in combination with malphalan/prednisone versus melphalan/prednisone in the treatment of multiple myeloma stages II and III: a randomized study fromthemyeloma group of central Sweden. Blood 1993; 81: 1428–34

    PubMed  CAS  Google Scholar 

  17. Mandelli F, Avvisati G, Amadori S, et al. Maintenance treatment with recombinant interferon alfa-2b in patients with multiple myeloma responding to conventional induction chemotherapy. N Engl J Med 1990; 322: 1430–4

    Article  PubMed  CAS  Google Scholar 

  18. Westin J, Rodjer S, Turesson I, et al. Interferon alpha-2b versus no maintenance therapy during the plateau phase in multiple myeloma: a randomized study. Br J Haematol 1995; 89: 561–8

    Article  PubMed  CAS  Google Scholar 

  19. Hjorth M, the Nordic Myeloma Study Group. Interferon α-2b added to melphalan-prednisolone for initial and maintenance therapy in multiple myeloma: a randomized, controlled trial. Ann Intern Med 1996; 124: 212–22

    Google Scholar 

  20. Browman GP, Bergsagel D, Sicheri D, et al. Randomized trial of interferon maintenance in multiple myeloma: a study of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 1995; 13: 2354–60

    PubMed  CAS  Google Scholar 

  21. Ludwig H, Cohen AM, Polliack A, et al. Interferon-alpha for induction and maintenance in multiple myeloma: results of two multicenter randomized trials and summary of other studies. Ann Oncol 1995; 6: 467–76

    PubMed  CAS  Google Scholar 

  22. Cooper MR, Dear K, Ross McIntyre R, 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

    PubMed  CAS  Google Scholar 

  23. Salmon SE, Crowley JJ, Grogan TM, et al. Combination chemotherapy, glucocorticoids, and interferon alfa in the treatment of multiple myeloma: a Southwest Oncology Group study. J Clin Oncol 1994; 12: 2405–14

    PubMed  CAS  Google Scholar 

  24. Drayson MT, Chapman CE, Dunn JA, et al. MRC trial of α2b interferon maintenance therapy in first plateau phase of multiple myeloma. Br J Haematol 1998; 101: 195–202

    Article  PubMed  CAS  Google Scholar 

  25. Wheatley K, the Myeloma Trialists’ Collaborative Group. The role of interferon (IFN) as therapy for multiple myeloma: an overview of 24 randomized trials with over 4000 patients [abstract]. Proc Am Soc Clin Oncol 1998; 17: 28

    Google Scholar 

  26. Wisløff F, Hjorth M, Kaasa S, et al. Effect of interferon on the health-related quality of life of multiple myeloma patients: results of a Nordic randomized trial comparing melphalanprednisone to melphalan-prednisone + α-interferon. Br J Haematol 1996; 94: 324–32

    Article  PubMed  Google Scholar 

  27. Trippoli S, Becagli P, Messori A, et al. Maintenance treatment with interferon in multiple myeloma. Clin Drug Invest 1997; 14: 392–9

    Article  CAS  Google Scholar 

  28. Zee B, Cole B, Li T, et al. Quality-adjusted time without symptoms or toxicity analysis of interferon maintenance in multiple myeloma. J Clin Oncol 1998; 16: 2834–9

    PubMed  CAS  Google Scholar 

  29. Ludwig H, Fritz E, Neuda J, et al. Patient preferences for interferon alfa in multiple myeloma. J Clin Oncol 1997; 15: 1672–9

    PubMed  CAS  Google Scholar 

  30. McElwain TJ, Powles RL. High dose intravenous melphalan for plasma cell leukaemia and myeloma. Lancet 1983; II: 822–4

    Article  Google Scholar 

  31. Gore ME, Selby PJ, Viner C, et al. Intensive treatment for multiple myeloma and criteria for complete remission. Lancet 1989; II: 879–82

    Article  Google Scholar 

  32. 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

    PubMed  CAS  Google Scholar 

  33. Nemunaitis JS, Singer J, et al. Recombinant granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for lymphoid cancer. N Engl JMed 1991; 324: 1773–8

    Article  CAS  Google Scholar 

  34. Schmitz N, Linch D, Dreger P, et al. Randomized trial of filgrastim-mobilized peripheral blood progenitor cell transplantation versus autologous bone-marrow transplantation in lymphoma patients. Lancet 1996; 347: 353–7

    Article  PubMed  CAS  Google Scholar 

  35. Beyer J, Schwella N, Zingsem J, et al. Hematopoietic rescue after high-dose chemotherapy using autologous peripheral blood progenitor cells or bone marrow: a randomized comparison. J Clin Oncol 1995; 13: 1328–35

    PubMed  CAS  Google Scholar 

  36. Uyl-de Groot CA, Ossenkoppele GJ, van Riet AAPM, et al. The costs of peripheral blood progenitor cell reinfusion mobilized by granulocyte colony-stimulating factor following high dose melphalan as compared with conventional therapy in multiple myeloma. Eur J Cancer 1994; 30A: 457–9

    Article  Google Scholar 

  37. Duncan N, Hewetson M, Powles R, et al. An economic evaluation of peripheral blood stem cell transplantation as an alternative to autologous bone marrow transplantation in multiple myeloma. Bone Marrow Transplant 1996; 18: 1175–8

    PubMed  CAS  Google Scholar 

  38. Spitzer G, Adkins D, Spencer V, et al. Randomized study of growth factors post-peripheral blood stem cell transplant: neutrophil recovery is improved with modest clinical benefit. J Clin Oncol 1994; 12: 661–70

    PubMed  CAS  Google Scholar 

  39. Klumpp T, Mangan K, Goldberg S, et al. Granulocyte colony-stimulating factor accelerates neutrophil engraftment following peripheral blood stem cell transplantation: a prospective, randomized trial. J Clin Oncol 1995; 13: 1323–7

    PubMed  CAS  Google Scholar 

  40. 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 of results. Br J Haematol 1998; 102: 495–502

    Article  PubMed  CAS  Google Scholar 

  41. Jagannath S, Vesole DH, Zhang M, et al. Feasibility and cost-effectiveness of outpatient autotransplants in multiple myeloma. Bone Marrow Transplant 1997; 20: 445–50

    Article  PubMed  CAS  Google Scholar 

  42. 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

    PubMed  CAS  Google Scholar 

  43. Bolwell B, Goormastic M, Dannley R, et al. G-CSF post-autologous progenitor cell transplantation: a randomized study of 5, 10, 16 μg/kg/day. BoneMarrow Transplant 1997; 19: 215–9

    CAS  Google Scholar 

  44. Jagannath S, Vesole DH, Glenn L, et al. Low-risk intensive therapy for multiple myeloma with combined autologous bone marrow and blood stem cell support. Blood 1992; 80: 1666–72

    PubMed  CAS  Google Scholar 

  45. Attal M, Harousseau J-L, Stoppa AM, et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. N Engl J Med 1996; 335: 91–7

    Article  PubMed  CAS  Google Scholar 

  46. Attal M, Harousseau JL, Stoppa AM, et al. High-dose therapy in multiple myeloma: an updated analysis of the IFM 90 protocol [abstract]. Blood 1997; 90: 418a

    Google Scholar 

  47. Lenhoff S, Turesson I, Hjorth M, the Nordic Myeloma Study Group, et al. Intensive therapy in newly diagnosed multiple myeloma patients below 60 years: a prospective, controlled, population based study [abstract]. Blood 1998; 92: 727a

    Google Scholar 

  48. Henon P, Donatini B, Eisenmann JC, et al. Comparative survival, quality of life and cost-effectiveness of intensive therapy with autologous blood cell transplantation or conventional chemotherapy in multiple myeloma. Bone Marrow Transplant 1995; 16: 19–25

    PubMed  CAS  Google Scholar 

  49. Gulbrandsen N, Wisløff F, the Nordic Myeloma Study Group. Health related quality of life of multiple myeloma patients treated with high dose chemotherapy and autologous peripheral blood stem cell transplantation [abstract]. Blood 1998; 92: 728a

    Google Scholar 

  50. Mainwaring PN, Horton C, Powles R, et al. Role of autologous transplantation in patients withmultiplemyeloma (MM) aged 65 and over [abstract]. Blood 1998; 92: 662a

    Google Scholar 

  51. De Arriba F, Heras I, Del Carmen Garcia M, et al. Economic costs of autotransplantation of hematopoietic progenitors. Med Clin 1996; 106: 329–32

    Google Scholar 

  52. Ager S, Scott MA, Mahendra P, et al. Peripheral blood stem cell transplantation after high-dose therapy in patients with malignant lymphoma: a retrospective comparison with autologous bone marrow transplantation. BoneMarrow Transplant 1995; 16: 79–83

    CAS  Google Scholar 

  53. Uyl-de Groot CA, Okhuijsen SY, Hagenbeek A, et al. Costs of introducing autologous BMT in the treatment of lymphoma and acute leukaemia in the Netherlands. Bone Marrow Transplant 1995; 15: 605–10

    PubMed  CAS  Google Scholar 

  54. Schulman KA. Economics of bone marrow transplantation. J Clin Oncol 1996; 14: 1409–10

    PubMed  CAS  Google Scholar 

  55. Smith TJ, Hillner BE, Schmitz N, et al. Economic analysis of a randomized clinical trial to compare filgrastim-mobilized peripheral-blood progenitor-cell transplantation and autologous bone marrow transplantation in patients with Hodgkin’s and non-Hodgkin’s lymphoma. J Clin Oncol 1997; 15: 5–10

    PubMed  CAS  Google Scholar 

  56. Trippoli S, Messori A, Becagli P, et al. Treatments for newly diagnosed multiple myeloma: analysis of survival data and cost-effectiveness evaluation. Oncol Rep 1998; 5: 1475–82

    PubMed  CAS  Google Scholar 

  57. Teeling Smith G. The economics of hypertension and stroke. Am Heart J 1990; 119: 725–8

    Article  Google Scholar 

  58. Torrance GW, FeenyD.Utilities and quality-adjusted life-years. Int J Technol Assess Health Care 1989; 5: 559–75

    Article  PubMed  CAS  Google Scholar 

  59. Smith TJ, Hillner BE, Desch CE. Efficacy and cost-effectiveness of cancer treatment: rational allocation of resources based on decision analysis. J Natl Cancer Inst 1993; 18: 1460–9

    Article  Google Scholar 

  60. Attal M, Payen C, Facon T, et al. Single versus double transplant in myeloma: a randomized trial of the Inter Groupe Francais du Myélome [abstract]. Blood 1997; 90: 418a

    Google Scholar 

  61. Cunningham D, Powles R, Viner C, et al. High dose chemotherapy and autologous bone marrow transplantation in multiple myeloma. Proc IV International Workshop on Multiple Myeloma; 1993 Oct 2–5; Rochester

  62. Gahrton G, Tura S, Ljungman P, et al. Allogeneic bone marrow transplantation in multiple myeloma. N Engl J Med 1991; 325: 1267–73

    Article  PubMed  CAS  Google Scholar 

  63. Björkstand B, Ljungman P, Svensson H, et al. Allogeneic bone marrow transplantation versus autologous stem cell transplantation in multiple myeloma: a retrospective case-matched study from the European Group for Blood andMarrow Transplantation. Blood 1996; 88: 4711–8

    Google Scholar 

  64. Lahtinen R, LaaksoM, Palva I, et al. Randomised, placebo-controlled multicentre trial of clodronate in multiple myeloma. Lancet 1992; 340: 1049–52

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  66. Brincker H, Westin J, Abildgaard N, et al. Failure of oral pamidronate to reduce skeletal morbidity in multiple myeloma: a double-blind placebo-controlled trial. Br J Haematol 1998; 101: 280–6

    Article  PubMed  CAS  Google Scholar 

  67. Laakso M, Lahtinen R, Virkkunen P, et al. Subgroup and cost-benefit analysis of the Finnish multicentre trial of clodronate in multiple myeloma. Br J Haematol 1994; 87: 725–9

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  69. Bruce NJ, McCloskey EV, Kanis JA, et al. Economic impact of using clodronate in the management of patients with multiple myeloma. Br J Haematol 1999; 104: 358–64

    Article  PubMed  CAS  Google Scholar 

  70. Bloomfield DJ. Should bisphosphonates be part of the standard therapy of patients with multi plemyeloma or bone metastases from other cancers? An evidence-based review. J Clin Oncol 1998; 16: 1218–25

    PubMed  CAS  Google Scholar 

  71. Fontana A, Herrmann Z, Menssen HD, et al. Effects of intravenous ibandronate therapy on skeletal related events and survival in patients with advanced multiple myeloma [abstract]. Blood 1998; 92: 106a

    Google Scholar 

  72. Garton JP, Gertz MA, Witzig TE, et al. Epoetin alfa for the treatment of anemia of multiple myeloma. Arch Intern Med 1995; 155: 2069–74

    Article  PubMed  CAS  Google Scholar 

  73. Österborg A, Boogaerts MA, Cimino R, et al. Recombinant human erythropoietin in transfusion-dependent anemic patients with multiple myeloma and non-Hodgkin’s lymphoma: a randomized multicenter study. Blood 1996; 87: 2675–82

    PubMed  Google Scholar 

  74. Chapel HM, Lee M, Hargreaves R, et al. Randomised trial of intravenous immunoglobulin as prophylaxis against infection in plateau-phase multiple myeloma. Lancet 1994; 343: 1059–63

    Article  PubMed  CAS  Google Scholar 

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Wisløff, F., Gulbrandsen, N. & Nord, E. Therapeutic Options in the Treatment of Multiple Myeloma. Pharmacoeconomics 16, 329–341 (1999). https://doi.org/10.2165/00019053-199916040-00002

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