Clinical Rheumatology

, Volume 25, Issue 2, pp 175–182 | Cite as

Do new therapeutic approaches (autotransplants, thalidomide, dexamethasone) improve the survival of patients with multiple myeloma followed in a rheumatology department?

  • S. El Mahou
  • B. Jamard
  • A. Constantin
  • A. Cantagrel
  • B. Maziéres
  • M. Laroche
  • M. Attal
  • C. Arnaud
Original Article

Abstract

Survival of patients with multiple myeloma (MM) showed no improvement between the 1960s and 1990s. During the last decade, new therapeutic approaches seemed likely to offer hope of prolonging survival. The aim of this study was to examine if this survival increased with the usage of new treatments. The method involves a retrospective study of 123 patients with MM, diagnosed between 1975 and 1999, all receiving treatment. They were divided into two groups: group 1 included 55 patients given the so-called “old treatments” [melphalan-prednisone, cyclophosphamide-prednisone, polychemotherapy (vincristine, melphalan, cyclophosphamide, prednisone (VMCP), VMCP-VBAP)], and group 2 included 68 patients receiving at least one of the so-called “new treatments” (dexamethasone, thalidomide, high-dose chemotherapy followed by autotransplants, bisphosphonates, interferon). The two groups were similar in terms of age, sex ratio and renal impairment, and the percentage of light-chain MM was identical in both groups. Patients who had been given a “new” treatment (group 2) had longer median survival than the patients in group 1 (54 vs 42 months). Independent analysis of each treatment modality showed increased median survival in MM patients treated using autotransplantation compared with untreated patients (125 vs 45 months). Survival was also longer in MM patients treated with thalidomide than in untreated patients (72 vs 42 months). On the other hand, neither bisphosphonates, interferon-alpha nor dexamethasone result in improved survival. Our findings emphasize the increased survival of the MM patients treated with new therapeutic approaches.

Keywords

Autotransplants Dexamethasone Multiple myeloma Polychemotherapy Survival Thalidomide 

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References

  1. 1.
    Bergsagel DE, Wong O, Bergsagel PL, Alexanian R, Anderson K, Kyle RA, Rabbe GK (1999) Benzene and multiple myeloma: appraisal of the scientific evidence. Blood 94:1174–1182PubMedGoogle Scholar
  2. 2.
    Jemal A, Thomas A, Murray T, Thun M (2002) Cancer statistics, 2002. CA Cancer J Clin 52:23–47PubMedCrossRefGoogle Scholar
  3. 3.
    Herrinton LJ, Weiss NS, Olshan AF (1995) The epidemiology of myeloma. In: Malpas JS, Bergsagel D, Kyle R (eds) Myeloma: biology and management. Oxford University Press, London, pp 127–168Google Scholar
  4. 4.
    Zaidi AA, Vesole DH (2001) Multiple myeloma: an old disease with new hope for the future. CA Cancer J Clin 51:273–285PubMedCrossRefGoogle Scholar
  5. 5.
    Kaufmann H, Urbauer E, Ackermann J, Huber H, Drach J (2001) Advances in the biology and therapeutic management of multiple myeloma. Ann Hematol 80:445–451PubMedCrossRefGoogle Scholar
  6. 6.
    Durie BG, Salmon SE (1975) A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer 36:842–854PubMedCrossRefGoogle Scholar
  7. 7.
    Rajkumar SV, Gertz MA, Kyle RA, Greipp PR (2002) Current therapy for multiple myeloma. Mayo Clin Proc 77:813–822PubMedCrossRefGoogle Scholar
  8. 8.
    Bataille R, Durie BG, Grenier J, Sany J (1986) Prognostic factors and staging in multiple myeloma: a reappraisal. J Clin Oncol 4:80–87PubMedGoogle Scholar
  9. 9.
    Blade J, Kyle RA, Greipp PR (1996) Presenting features and prognosis in 72 patients with multiple myeloma who were younger than 40 years. Br J Haematol 93:345–351PubMedCrossRefGoogle Scholar
  10. 10.
    Smith ML, Newland AC (1999) Treatment of myeloma. QJM 92:11–14PubMedCrossRefGoogle Scholar
  11. 11.
    Alexanian R, Bergsagel DE, Migliore PJ, Vaughn WK, Howe CD (1968) Melphalan therapy for plasma cell myeloma. Blood 31:1–10PubMedGoogle Scholar
  12. 12.
    Alexanian R, Haut A, Khan AU, Lane M, McKelvey EM, Migliore PJ, Stuckey WJ Jr, Wilson HE (1969) Treatment for multiple myeloma. Combination chemotherapy with different melphalan dose regimens. JAMA 208:1680–1685PubMedCrossRefGoogle Scholar
  13. 13.
    Nara N (1995) Current and future approaches to therapy for multiple myeloma. Gan To Kagaku Ryoho 22:9–15PubMedGoogle Scholar
  14. 14.
    Bataille R, Souteyrand P, Sany J (1984) Clinical evaluation of response or escape to chemotherapy and of survival of patients with multiple myeloma. A prospective study of 202 patients (1975–1982). Anticancer Res 4:339–345PubMedGoogle Scholar
  15. 15.
    Karjalainen S, Palva I (1989) Do treatment protocols improve end results? A study of survival of patients with multiple myeloma in Finland. BMJ 299:1069–1072PubMedCrossRefGoogle Scholar
  16. 16.
    Locatelli F, Giovanelli E, Neretto G, Furno F, Pellerito R (1979) Survival and therapy of multiple myeloma. A propos of 56 observed cases. Minerva Med 70:925–933PubMedGoogle Scholar
  17. 17.
    Salmon SE, Haut A, Bonnet JD, Amare M, Weick JK, Durie BG, Dixon DO (1983) Alternating combination chemotherapy and levamisole improves survival in multiple myeloma. J Clin Oncol 1:453–461PubMedGoogle Scholar
  18. 18.
    MacLennan IC, Chapman C, Dunn J, Kelly K (1992) Combined chemotherapy with ABCM versus melphalan for treatment of myelomatosis. Lancet 339:200–205PubMedCrossRefGoogle Scholar
  19. 19.
    Oken MM, Harrington DP, Abramson N, Kyle RA, Knospe W, Glick JH (1997) Comparison of melphalan and prednisone with vincristine, carmustine, melphalan, cyclophosphamide, and prednisone in the treatment of multiple myeloma: results of Eastern Cooperative Oncology Group Study E2479. Cancer 79:1561–1567PubMedCrossRefGoogle Scholar
  20. 20.
    Boccadoro M, Marmont F, Tribalto M, Avvisati G, Andriani A, Barbui T, Cantonetti M, Carotenuto M, Comotti B, Dammacco F (1991) Multiple myeloma: VMCP/VBAP alternating combination chemotherapy is not superior to melphalan and prednisone even in high-risk patients. J Clin Oncol 9:444–448PubMedGoogle Scholar
  21. 21.
    Hjorth M, Holmberg E, Rodjer S, Turesson I, Westin J, Wisloff F (1999) Survival in conventionally treated younger (<60 years) multiple myeloma patients: no improvement during two decades. Eur J Haematol 62:271–277PubMedCrossRefGoogle Scholar
  22. 22.
    Gregory WM, Richards MA, Malpas JS (1992) Combination chemotherapy versus melphalan and prednisolone in the treatment of multiple myeloma: an overview of published trials. J Clin Oncol 10:334–342PubMedGoogle Scholar
  23. 23.
    Myeloma Trialists’ Collaborative Group (1998) Combination chemotherapy versus melphalan plus prednisone as treatment for multiple myeloma: an overview of 6,633 patients from 27 randomised trials. J Clin Oncol 16:3832–3842Google Scholar
  24. 24.
    Samson D, Gaminara E, Newland A, Van de Pette J, Kearney J, McCarthy D, Joyner M, Aston L, Mitchell T, Hamon M (1989) Infusion of vincristine and doxorubicin with oral dexamethasone as first-line therapy for multiple myeloma. Lancet 2:882–885PubMedCrossRefGoogle Scholar
  25. 25.
    Alexanian R, Dimopoulos MA, Delasalle K, Barlogie B (1992) Primary dexamethasone treatment of multiple myeloma. Blood 80:887–890PubMedGoogle Scholar
  26. 26.
    Mellstedt H, Ahre A, Bjorkholm M, Holm G, Johansson B, Strander H (1979) Interferon therapy in myelomatosis. Lancet 1:245–247PubMedCrossRefGoogle Scholar
  27. 27.
    Cooper MR, Dear K, McIntyre OR, Ozer H, Ellerton J, Canellos G, Bernhardt B, Duggan D, Faragher D, Schiffer C (1993) 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 11:155–160PubMedGoogle Scholar
  28. 28.
    Osterborg A, Bjorkholm M, Bjoreman M, Brenning G, Carlson K, Celsing F, Gahrton G, Grimfors G, Gyllenhammar H, Hast R (1993) 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 81:1428–1434PubMedGoogle Scholar
  29. 29.
    Oken MM, Leong T, Lenhard RE, Greipp PR, Kay NE, Van Ness B, Keimowitz RM, Kyle RA (1999) The addition of interferon or high dose cyclophosphamide to standard chemotherapy in the treatment of patients with multiple myeloma: phase III Eastern Cooperative Oncology Group Clinical Trial EST 9486. Cancer 86:957–968PubMedCrossRefGoogle Scholar
  30. 30.
    Mandelli F, Avvisati G, Amadori S, Boccadoro M, Gernone A, Lauta VM et al (1990) Maintenance treatment with recombinant interferon alfa-2b in patients with multiple myeloma responding to conventional induction chemotherapy. N Engl J Med 322:1430–1434PubMedGoogle Scholar
  31. 31.
    Pulsoni A, Avvisati G, Petrucci MT, Mandelli F, Giannarelli D, Lauta VM, Tribalto M, Pileri A (1998) The Italian experience on interferon as maintenance therapy in multiple myeloma: ten years after. Blood 92:2184–2186PubMedGoogle Scholar
  32. 32.
    Myeloma Trialists’ Collaborative Group (2001) Interferon as therapy for multiple myeloma: an individual patient data overview of 24 randomized trials and 4012 patients. Br J Haematol 113:1020–1034CrossRefGoogle Scholar
  33. 33.
    Blade J, Esteve J (2000) Viewpoint on the impact of interferon in the treatment of multiple myeloma: benefit for a small proportion of patients? Med Oncol 17:77–84PubMedCrossRefGoogle Scholar
  34. 34.
    Bjorkstrand B, Ljungman P, Bird JM, Samson D, Brandt L, Alegre A, Auzanneau G, Blade J, Brunet S, Carlson K (1995) Autologous stem cell transplantation in multiple myeloma: results of the European Group for Bone Marrow Transplantation. Stem Cell 13 [Suppl 2]: 140–146Google Scholar
  35. 35.
    Fernand JP, Ravaud P, Chevret S, Divine M, Leblond V, Belanger C, Macro M, Pertuiset E, Dreyfus F, Mariette X, Boccacio C, Brouet JC (1998) High-dose therapy and autologous peripheral blood stem cell transplantation in multiple myeloma: up-front or rescue treatment? Results of a multi-center sequential randomized clinical trial. Blood 92:3131–3136Google Scholar
  36. 36.
    Sirohi B, Powles R, Treleaven J, Mainwaring P, Kulkarni S, Pandha H, Bhagwati N, Horton C, Singhal S, Mehta J (2000) The role of autologous transplantation in patients with multiple myeloma aged 65 years and over. Bone Marrow Transplant 25:533–539PubMedCrossRefGoogle Scholar
  37. 37.
    Shipman CM, Croucher PI, Russell RG, Helfrich MH, Rogers MJ (1998) The bisphosphonate incadronate (YM175) causes apoptosis of human myeloma cells in vitro by inhibiting the mevalonate pathway. Cancer Res 58:5294–5297PubMedGoogle Scholar
  38. 38.
    Berenson JR (2001) New advances in the biology and treatment of myeloma bone disease. Semin Hematol 38:15–20PubMedCrossRefGoogle Scholar
  39. 39.
    Dallas SL, Garrett IR, Oyajobi BO, Dallas MR, Boyce BF, Bauss F, Radl J, Mundy GR (1999) Ibandronate reduces osteolytic lesions but not tumor burden in a murine model of myeloma bone disease. Blood 93:1697–1706PubMedGoogle Scholar
  40. 40.
    Lahtinen R, Laakso M, Palva I, Virkkunen P, Elomaa I (1992) Randomised, placebo-controlled multicentre trial of clodronate in multiple myeloma. Finnish Leukaemia Group. Lancet 340:1049–1052PubMedCrossRefGoogle Scholar
  41. 41.
    Singhal S, Mehta J, Desikan R, Ayers D, Roberson P, Edd-lemon P, Munshi N, Anaissie E, Wilson C, Dhodapkar, Zeddis J, Barlogie B (1999) Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med 341:1565–1571PubMedCrossRefGoogle Scholar
  42. 42.
    Raje N, Anderson K (1999) Thalidomide—a revival story. N Engl J Med 341:1606–1609PubMedCrossRefGoogle Scholar
  43. 43.
    McElwain TJ, Powles RL (1983) High-dose intravenous melphalan for plasma-cell leukaemia and myeloma. Lancet 2:822–824PubMedCrossRefGoogle Scholar
  44. 44.
    Barlogie B, Alexanian R, Dicke KA, Zagars G, Spitzer G, Jagannath S, Horwitz L (1987) High-dose chemoradiotherapy and autologous bone marrow transplantation for resistant multiple myeloma. Blood 70:869–872PubMedGoogle Scholar
  45. 45.
    Moreau P, Facon T, Attal M et al (2002) Superiority of 200 mg/m2 melphalan over 8 Gy total body irradiation plus 140 mg/m2 as conditioning regimens for peripheral blood stem cell transplantation in patients with newly diagnosed myeloma. Blood (in press)Google Scholar
  46. 46.
    Moreau P, Facon T, Attal M, Hulin C, Michallet M, Maloisel F, Sotto JJ, Guilhot F, Marit G, Doyen C, Jaubert J, Fuzibet JG, Francois S, Benboubker L, Monconduit M, Voillat L, Macro M, Berthou C, Dorvaux V, Pignon B, Rio B, Matthes T, Casassus P, Caillot D, Najman N, Grosbois B, Bataille R, Harousseau JL, Intergroupe Francophone du Myelome (2002) 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 99:731–735PubMedCrossRefGoogle Scholar
  47. 47.
    Gahrton G, Tura S, Ljungman P, Blade J, Brandt L, Cavo M, Facon T, Gratwohl A, Hagenbeek A, Jacobs P (1995) Prognostic factors in allogeneic bone marrow transplantation for multiple myeloma. J Clin Oncol 13:1312–1322PubMedGoogle Scholar
  48. 48.
    Bjorkstrand BB, Ljungman J, Svensson H, Hermans J, Alegre A, Apperley J, Blade J, Carlson K, Cavo M, Ferrant A, Goldstone AH, de Laurenzi A, Majolino I, Marcus R, Prentice HG, Remes K, Samson D, Sureda A, Verdonck LF, Volin L, Gahrton G (1996) Allogeneic bone marrow transplantation versus autologous stem cell transplantation in multiple myeloma: a retrospective case-matched study from the European Group for Blood and Marrow Transplantation. Blood 88:4711–4718PubMedGoogle Scholar
  49. 49.
    Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF, Casassus P, Maisonneuve H, Facon T, Ifrah N, Payen C, Bataille R (1996) A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. N Engl J Med 335:91–97PubMedCrossRefGoogle Scholar
  50. 50.
    Vesole DH, Tricot G, Jagannath S, Desikan KR, Siegel D, Bracy D, Miller L, Cheson B, Crowley J, Barlogie B (1996) Autotransplants in multiple myeloma: what have we learned? Blood 88:838–847PubMedGoogle Scholar
  51. 51.
    Barlogie B, Jagannath S, Desikan KR, Mattox S, Vesole D, Siegel D, Tricot G, Munshi N, Fassas A, Singhal S, Mehta J, Anaissie E, Dhodapkar D, Naucke S, Cromer J, Sawyer J, Epstein J, Spoon D, Ayers D, Cheson B, Crowley J (1999) Total therapy with tandem transplants for newly diagnosed multiple myeloma. Blood 93:55–65PubMedGoogle Scholar
  52. 52.
    Siegel DS, Desikan KR, Mehta J, Singhal S, Fassas A, Munshi N, Anaissie E, Naucke S, Ayers D, Spoon D, Vesole D, Tricot G, Barlogie B (1999) Age is not a prognostic variable with autotransplants for multiple myeloma. Blood 93:51–54PubMedGoogle Scholar
  53. 53.
    Bergsagel DE (1989) Is aggressive chemotherapy more effective in the treatment of plasma cell myeloma? Eur J Cancer Clin Oncol 25:159–161PubMedCrossRefGoogle Scholar
  54. 54.
    Richardson PG, Berenson J, Irwin D et al (2001) Phase 2 study of PS341, a novel proteasome inhibitor, alone or in combination with dexamethasone in patients with multiple myeloma who have relapsed following front-line therapy and are refractory to their most recent therapy. Blood 98:774aGoogle Scholar
  55. 55.
    Moehler TM, Neben K, Hawighorst H et al (2000) Thalidomide plus CED chemotherapy as salvage therapy in poor prognostic multiple myeloma in blood. In: Proceedings of the 42nd Annual Meeting and Exposition of the American Society of Hematology. WB Saunders, San Francisco 96:290bGoogle Scholar
  56. 56.
    Reichardt VL, Okada CY, Liso A, Benike CJ, Stockerl-Gold-stein KE, Engleman EG, Blume KG, Levy R (1999) Idiotype vaccination using dendritic cells after autologous peripheral blood stem cell transplantation for multiple myeloma—a feasibility study. Blood 93:2411–2419PubMedGoogle Scholar
  57. 57.
    Attal M, Harousseau JL, Facon T, Guilhot F, Doyen C, Fuzibet JG, Monconduit M, Hulin C, Caillot D, Bouabdallah R, Voillat L, Sotto JJ, Grosbois B, Bataille R, InterGroupe Francophone du Myelome (2003) Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med 349:2495–2502PubMedCrossRefGoogle Scholar

Copyright information

© Clinical Rheumatology 2006

Authors and Affiliations

  • S. El Mahou
    • 1
  • B. Jamard
    • 1
  • A. Constantin
    • 1
  • A. Cantagrel
    • 1
  • B. Maziéres
    • 1
  • M. Laroche
    • 1
  • M. Attal
    • 2
  • C. Arnaud
    • 3
  1. 1.Rheumatology DepartmentRangueil University Hospital, CHU RangueilToulouse Cedex 9France
  2. 2.Haematology DepartmentPurpan University HospitalToulouseFrance
  3. 3.Epidemiology DepartmentPurpan University HospitalToulouseFrance

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