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Dtsch Med Wochenschr 2000; 125(40): 1201-1209
DOI: 10.1055/s-2000-7695
Aktuelle Diagnostik & Therapie
Aktuelle Diagnostik & Therapie
© Georg Thieme Verlag Stuttgart · New York

Aktuelle Therapiekonzepte bei Patienten mit multiplem Myelom

A. Heyll, P. Schneider, U. Bauser, G. Kobbe, A. Hünerlitürkoglu, C. Aul, R. Haas
  • Klinik für Hämatologie Onkologie und klinische Immunologie, Medizinische Klinik und Poliklinik (Direktor: Prof. Dr. R. Haas), Universität Düsseldorf
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Publication Date:
31 December 2000 (online)

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Auch heute noch gibt es für Patienten mit multiplem Myelom kein Therapieverfahren mit einem gesicherten kurativen Potential. Im Gegensatz zu den 70er und 80er Jahren, in denen sich seit Einführung der Therapie mit Melphalan und Prednison durch Alexanian kein relevanter Therapiefortschritt ergeben hat, konnte all durch Etablierung von Hochdosischemotherapie mit Blutstammzelltransplantation eine signifikante Verbesserung der Überlebenszeit bei jüngeren Patienten erreicht werden. Weitere Verbesserungen der Therapieergebnisse haben sich insbesondere durch die Gabe von Bisphosphonaten und α-Interferon ergeben. Vor dem Hintergrund dieser aktuellen Entwicklungen soll ein Überblick über die derzeit möglichen Therapieoptionen bei Patienten mit multiplem Myelom gegeben werden.

Literatur

  • 1 Alexanian R, Dimopoulos M A, Delasalle K, Barlogie B. Primary dexamethasone treatment of multiple myeloma.  Blood. 1992;  80 887-889
    Search in Google Scholar
  • 2 Alexanian R, Dimopoulos M. The treatment of multiple myeloma.  N Engl J Med. 1994;  330 484-489
    Search in Google Scholar
  • 3 Attal M, Harousseau J L, Stoppa A M, Sotto J J, Fuzibet J G, Rossi J F, Casassus P, Maisonneuve H, Facon T, Ifrah N, Payen C, Bataille R. intergroupe francais du myelome . A prospective randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma.  N Engl J Med. 1996;  335 91-97
    Search in Google Scholar
  • 4 Attal M, Payen C, Facon T, Michaux J L, Guilhot F, Moconduit M, Fuzibet J G, Caillot D, Dorvaux V, Harrousseau J L, Cahn J Y, Grobois B, Stoppa A M, Ifrah N, Sotto J H, Pignon B, Bataille R. Single versus double transplant in multiple myeloma: A randomized trial of the »Intergroupe Francais du Myélome« (IFM).  Blood. 1997;  90 (Suppl. 1) 418a
    Search in Google Scholar
  • 5 Aul C, Gattermann N, Germing U, Heyll A. Adverse of interferon treatment. Aul C, Schneider Interferons Springer: Berlin; 1997: 250-266.
    Search in Google Scholar
  • 6 Barlogie B, Smith L, Alexanian R. Effective treatment of advanced multiple myeloma refractory to alkylating agents.  N Engl Med. 1984;  310 1351-1360
    Search in Google Scholar
  • 7 Barlogie B, Beck T. Recombinant human erythropoietin and the anemia of multiple myeloma.  Stem Cells. 1993;  11 88-94
    Search in Google Scholar
  • 8 Barlogie B, Jagannath S, Vesole D, Tricot G :. Autologous in multiple myeloma. Ammaccon F, Barlogie Multiple myeloma and realted disorders Ares-Serono Symposia: Rom; 1994: 194-216.
    Search in Google Scholar
  • 9 Barlogie B, Jagannath S, Vesole D H, Naucke S, Cheson B, Mattox S, Bracy D, Salmon S, Jacobson J, Crowley J, Tricot G. Superiority of tandem autologous transplantation over standard therapy vor previously untreated myeloma.  Blood. 1997;  89 789-793
    Search in Google Scholar
  • 10 Bataille R, Boccadoro M, Klein B, Durie B, Pileri A. C-reactive protein and beta-2-mikroglobulin produce a simple and powerful myeloma staging system.  Blood. 1992;  80 733-737
    Search in Google Scholar
  • 11 Belch A R, Eisenhauer E A, Muldal A, Browman G, Klasa R, Osterwalder B. Phase-II study of subcutaneous rhu-interleukin-2 and rhu-interferon alpha-2a in previously treated patients with multiple myeloma.  Ann Oncol. 1995;  6 721-723
    Search in Google Scholar
  • 12 Berenson J R, Lichtenstein A, Porter L, Dimopoulos M, Bordoni R, George S, Lipton A, Keller A, Ballester O, Kovacs M J, Blacklock H A, Bell R, Simeone J, Reitsma D J, Heffernan M, Seaman J, Knight R D. Myeloma Aredia Study Group . Efficiacy of pamidronate in reducing skeletal events in patients with advanced multiple myeloma.  N Engl J Med. 1996;  334 529-530
    Search in Google Scholar
  • 13 von den Berg B C, Lecouvet F E, Michaux L, Labaisse M, Malghem J, Jamart J, Maldague B E, Ferrant A, Michaux J L. Stage I multiple myeloma: value of MR imaging of the bone marrow in the determination of prognosis.  Radiology. 1996;  201 243-246
    Search in Google Scholar
  • 14 Bergsagel D E, Rider W D. Plasma cell neoplasms. De Vita VT, Hellman S, Rosenberg SA Cancer J. B. Lippincott Company: Philadelphia; 1982: 1439-1475.
    Search in Google Scholar
  • 15 Björkstrand B, Ljungman P, Svensson H, Hermans J, Alegre A, Apperly J, Bladé J, Carlson K, Cavo M, Ferrant A, Goldstone A H, de Laurenzi A, Majolino I, Marcus R, Prentice H G, Remes K, Samson D, Sureda A, Verdonck L F, Volin L, Gahrton G. Allogeneic bone marrow transplantation versus autologous stem cell transplantation in multiple myeloma: A retrospective case-matched study from the european Group for Blood and Bone Marrow Transplantation.  Blood. 1996;  88 4711-4718
    Search in Google Scholar
  • 16 Björkstrand B, Svensson H, Ljungman P, Apperly J, Goldschmidt H, Remes K, Alegre A, Marcus R, Carlson K, Coser P, Sureda A, Barbui T, Goldstone A H, Bladé J, Volin L, Boogaerts M, Lenhoff S, Majolino I, Samson D, de Laurenzi A, San M iguel JF, Gahrton G. Autologous stem cell transplantation in multiple myeloma - The EBMT registry update.  Bone Marrow Transplant. 1998;  21 (Suppl. 1) 208
    Search in Google Scholar
  • 17 Bladé J, San M iguel JF, Alcalá A, Maldonodo J, Sanz M S, Gracía-CondeJ, Moro M S, Alonso C, Besalduch J, Zubizarreta A, Besses C, González-Brito G, Hernández-Martín J, Fernández-Calvo J, Rubio D, Ortega F, Jiménez R, Colominas P, Faura M V, Font L, Tortosa J, Domingo A, Fontanillas M, Rozman C, Estapé J. Alternating combination VCMP/VBAP chemotherapy versus melphalan/prednisone in the treatment of multiple myeloma: A randomized multicentric study of 487 patients.  J Clin Oncol. 1993;  11 1165-1171
    Search in Google Scholar
  • 18 Bremer K. Bendamustin a promising alkylating agent non cross-resistant to other alkylators in low grade Non-Hodgkin-Lymphomas.  Onkologie. 1994;  17 (Suppl. 2) 64
    Search in Google Scholar
  • 19 Brincker H, Westin J, Abildgaard N, Gimsing P, Turesson I, Hedemus M, Ford J, Kandra A. Failure of oral pamidronate to reduce skeletal morbidity in multiple myeloma: A double-blind placebo-controlled trial.  Br J Haemat. 1998;  101 280-286
    Search in Google Scholar
  • 20 Browman G P, Bergsagel D, Sicheri D, O¿Reilly S, Wilson K S, rubin S, Belch A, Shustik C, Barr R, Walker I, James K, Zee B, Johnston D. Randomized trial of interferon maintenance in multiple myeloma: A study of the national Cancer Institute of Canada Clinical Trial Groups.  J Clin Oncol. 1995;  13 2354-2360
    Search in Google Scholar
  • 21 Cazzalo M, Messinger D, Battistel V, Bron D, Cimino R, Enller-Ziegler  L, Essers U, Greil R, Grossi A, Jäger G, LeMevel A, Najman A, Silingardi V, Spriano M, van Hoof A, Ehmer B. Recombinant human erythropoietin in the anemia associated with multiple myeloma or non-Hodgkin¿s lymphoma: dose finding and identification of predictors of response.  Blood. 1995;  86 4446-4453
    Search in Google Scholar
  • 22 Cook G, Sharp R A, Tansey T, Franklin I M. A phase I/II trial of Z-Dex (oral idarubicin and dexamethasone) an oral equivalent of VAD, as an initial therapy at diagnosis or progression in multiple myeloma.  Br J Haemat. 1996;  93 931-934
    Search in Google Scholar
  • 23 Dimopoulos M A, Barlogie B, Smith T L, Alexanian R. High serum lactate dehydrogenase level as a marker for drug resistance and short survival im multiple myeloma.  Ann Int Med. 1991;  115 931-935
    Search in Google Scholar
  • 24 Durie B G, Salmon S E. A clinical staging system for multiple myeloma.  Cancer (Philad.). 1975;  36 842-854
    Search in Google Scholar
  • 25 Einsele H, Bamberg M, Zander A, Kröger N, Budach W, Schmidt H, Schmidberger H, Hebart H, Trümper L, Müller W, Schlimok G, Hertenstein B, Peest D, Metzner B, Frickhofen N, Kanz L. Total marrow irradiation, busulfan and cyclophosphamide followed by PBSCT in patients with multiple myeloma.  Blood. 1998;  92 (Suppl. 1) 128a
    Search in Google Scholar
  • 26 Glasmacher A, Haferlach T, Gorschlüter M, Mezger J, Maintz C, Clemens M R, Ho Y, Übelacker R, Kleinschmidt R, Gieseler F. Oral idarubicin, dexamethasone and vincristine (VID) in the treatment of multiple myeloma.  Leukemia. 1997;  11 (Suppl. 5) 22-26
    Search in Google Scholar
  • 27 Gregory W M, Richards M A, Malpas J S. Combination therapy versus melphalan and prednisolone in the treatment of multiple myeloma: An overview of published trials.  J Clin Oncol. 1992;  10 334-342
    Search in Google Scholar
  • 28 Greipp P R, Katzmann J A, O¿Fallon W M, Kyle R A. Value of beta-2-mikroglobulin level and plasma cell labeling indices as prognostic factors in patients with newly diagnosed myeloma.  Blood. 1988;  72 219-223
    Search in Google Scholar
  • 29 Harley J B, Pajak T F, Mcintyre O R, Kochwa S, Cooper M R, Coleman M, Cuttner J. Improved survival of increased-risk myeloma patients on combined triple-alkylating-agent therapy: A study of the CALGB.  Blood. 1979;  54 13-22
    Search in Google Scholar
  • 30 Heyll A, Söhngen D, Kobbe G, Schneider P, Bauser U, Thiele K P, Wehmeier A, Südhoff T, Quenzel E M, Rieth C, Wernet P, Fischer J, Frick M, Aul C. Idarubicin, melphalan and cyclophosphamide: An intensified high dose regimen for the treatment of myeloma patients.  Leukemia. 1997;  11 (Suppl. 5) 32-34
    Search in Google Scholar
  • 31 Hjorth M, Hellquist L, Holmberg E, Magnusson B, Rödjer S, Westin J. Myeloma Group of Estern Sweden . Initial treatment in multiple myeloma: No advantage of multidrug chemotherapy over melphalan-prednisone.  Br J Haemat. 1990;  74 185-191
    Search in Google Scholar
  • 32 Jagannath  S, Barlogie B, Dicke K, Alexanian R, Zagars G, Cheson B, Lemaistre F C, Smallwood L, Pruitt K, Dixon D O. Autologous bone marrow transplantation in multiple myeloma: Identification of prognostic factors.  Blood. 1990;  76 1860-1866
    Search in Google Scholar
  • 33 Joshua D E, Penny R, Matthews J P, Laidlaw C R, Gibson J, Bradstock K, Wolf M, Goldstein D. Australian Leukemia Study Group Myeloma II: A randomized trial of intensive combination chemotherapy with or without interferon in patients with myeloma.  Br J Haemat. 1997;  97 38-45
    Search in Google Scholar
  • 34 Lathinen R, Laakso M, Palva I, Virkkunen P, Elomaa  I. Finnish Leukaemia Group . Randomized, placebo-controlled multicenter trial of clodronate in multiple myeloma.  Lancet. 1992;  340 1049-1052
    Search in Google Scholar
  • 35 Liebross R H, Ha C S, Cox J D, Weber D, Delasalle K, Alexanian R. Solitary bone plasmocytoma: Outcome and prognostic factors following radiotherapy.  Int J Radiat Oncol Biol Phys. 1998;  41 1063-1067
    Search in Google Scholar
  • 36 Ludwig H, Cohen A M, Polliack A, Huber H, Nachbaur D, Senn H J, Morant R, Eckhardt S, Günczler P, Seewann H L, Schüller J, Rhyner R, Cavalli F, Fritz E. Interferon-alpha for induction an maintenance in multiple myeloma: Results of two multicenter randomized trials and summary of other studies.  Ann Oncol. 1995;  6 467-476
    Search in Google Scholar
  • 37 Ludwig H, Fritz E, Kotzmann H, Hocker P, Gisslinger H, Barnas U. Erythropoietin treatment of anemia associated with multiple myeloma.  N Engl J Med. 1990;  322 1693-1699
    Search in Google Scholar
  • 38 Medical Research Council Working Party on Leukemia in Adults (Prepared by I.M.C. MacLennan and J. Cusick) . Objective evaluation of the role of vincristine in induction and maintenance therapy for myelomatosis.  Br J Cancer. 1985;  52 153-158
    Search in Google Scholar
  • 39 Mittelman M, Zeidman A, Fradin Z, Magazanik A, Lewinski U H, Cohen A. Recombinant human erythropoietin in the treatment of multiple myeloma associated anemia.  Acta Haematol. 1997;  98 204-210
    Search in Google Scholar
  • 40 Moupopoulos L A, Dimopoulos M A, Smith T L, Weber D M, Delsalle K B, Lipshitz H I, Alexanian R. Prognostic significance of magnetic resonance imaging in patients with asymptomatic multiple myeloma.  J Clin Oncol. 1995;  13 251-256
    Search in Google Scholar
  • 41 The Nordic Myeloma Study Group . Interferon-α2b added to melphalan-prednisone for initial and maintenance therapy in multiple myeloma.  Ann Int Med. 124 1996;  212-222
    Search in Google Scholar
  • 42 Österborg A, Boogaerts M A, Cimino R, Essers U, Holowiecki J, Juliusson G, Jäger G, Najman A, Peest D. European Study Group of Erythropoietin . Treatment in multiple myeloma and non-Hodgkin¿s lymphoma.  Blood. 1996;  87 2675-2682
    Search in Google Scholar
  • 43 Österborg A, Yi Q, Henriksson L, Fagerberg J, Bergenbrant S, Jedditehrani M, Ruden U, Lefvert A K, Holm G, Mellstedt H. Idiotype immunization combined with granulocyte-makrophage colony-stimulating factor in myeloma patients induce type I, major histocompatibility complex-restricted, CD8- and CD4-specific T-cell responses.  Blood. 1998;  91 2459-2466
    Search in Google Scholar
  • 44 Ozaki S, Kosaka M, Watatsuki S, Abe M, Koishihara Y, Matsumoto T. Immuntherapy of multiple myeloma with a monoclonal antibody directed against a plasma cell-specific antigen, HM1.24.  Blood. 1997;  90 3179-3186
    Search in Google Scholar
  • 45 Palumbo A, Boccardo M, Bruno B, Tirolo S, Pileri A. Cyclophosphamide (3.6 g/m2) therapy with G-CSF support for resistent myeloma.  Haematologica. 1994;  79 513-518
    Search in Google Scholar
  • 46 Peest D, Deicher H, Coldewey R, Schmoll H J, Schedel I. Induction and maintenance therapy in multiple myeloma: A multicenter trial of MP versus VCMP.  Eur J Clin Oncol. 1988;  24 1061-1067
    Search in Google Scholar
  • 47 Peest D, Leo R, Bloche S, Hein R, Stannatkiessling S, Tschechene B, Fett W, Harms P, Hoffmann L, Bartl R, Wacker H H, Gorg S, Atzpodien J, Kirchner H, Deicher H. Low-dose recombinant interleukin-2 therapy in advanced multiple myeloma.  Br J Haematol. 1995;  89 328-337
    Search in Google Scholar
  • 48 Powels R, Raje N, Cunningham D, Malpas J, Milan S, Horton C, Mehra J, Singhal S, Viner C, Treleaven J. Maintenance therapy for remission in myeloma with Intron-A following melphalan and either an autologous bone marrow transplantation or peripheral stem cell rescue.  Stem Cells. 1995;  13 (Suppl. 2) 114-117
    Search in Google Scholar
  • 49 Saggio I, Ciappino L, Savino R, Ciliberto G, Perricaudet M. Adenovirus-mediated gene transfer of a human IL-6 antagonist.  Gene Ther. 1997;  4 839-845
    Search in Google Scholar
  • 50 Siegel D S, Deskian K R, Metha J, Singhal S, Fassas A, Munshi N, Anaisse E, Naucke S, Ayers D, Spoon D, Vesole D, Tricot G, Barlogie B. Age ist not a prognostic variable with autotransplants for multiple myeloma.  Blood. 1999;  93 51-54
    Search in Google Scholar
  • 51 Singhal S, Metha J, Eddlemon P, Gray P, Cromer J, Desikan R, Ayers D, Siegel D, Munshi N, Anaissie E, Katerjian H, Zeldis J, Barlogie B. Marked anti-tumor effect from antiangiogenesis therapy with thalidomide in high risk refractory multiple myeloma.  Blood. 1998;  92 (Suppl. 1) 318a
    Search in Google Scholar
  • 52 Vesole D H, Barlogie B, Jagannath S, Cheson B, Tricot G, Alexanian R, Crowley J. High-dose therapy for refractory mutliple myeloma: Improved prognosis with better supportive care and double transplants.  Blood. 1994;  84 950-956
    Search in Google Scholar

Korrespondenz

Prof. Dr. Axel Heyll

Klinik für Hämatologie, Onkologie und klinische Immunologie Medizinische Klinik und Poliklinik Universität Düsseldorf

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