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Der Internist

, Volume 60, Issue 1, pp 23–33 | Cite as

Primärtherapie beim Multiplen Myelom

  • I. BreitkreutzEmail author
  • M. Raab
  • H. Goldschmidt
Schwerpunkt: Multiples Myelom
  • 270 Downloads

Zusammenfassung

Die Therapielandschaft des neu diagnostizierten multiplen Myeloms hat sich im Verlauf der letzten beiden Jahrzehnte entscheidend verändert. Die Einführung der Hochdosistherapie mit Melphalan und nachfolgender autologer Blutstammzelltransplantation führte zunächst zu einem verbesserten Gesamtüberleben bei jüngeren Patienten, darüber hinaus scheinen nun insbesondere Hochrisikopatienten von einer Tandemtransplantation zu profitieren. Der Risikostratifizierung zum Zeitpunkt der Therapieeinleitung wird daher eine besondere Bedeutung beigemessen. Die Integration der sogenannten „neuen Substanzen“, wie Thalidomid, Lenalidomid und Bortezomib, in die Erstlinientherapie eröffnete sowohl Patienten, die für eine Hochdosistherapie geeignet sind, als auch nicht transplantationsfähigen Patienten neue Perspektiven. Standardinduktion in Deutschland vor geplanter Hochdosistherapie ist derzeit eine Kombination von Bortezomib, Cyclophosphamid und Dexamethason, jedoch wird zunehmend die Kombination von Lenalidomid, Bortezomib und Dexamethason angewendet. Für nicht transplantationsfähige Patienten stehen in der Erstlinientherapie Kombinationen mit Bortezomib oder Lenalidomid zur Verfügung. Erstmalig in der Primärtherapie dieser Patienten wurde kürzlich eine Therapie mit dem Anti-CD38-Antikörper Daratumumab in Kombination mit Bortezomib, Melphalan und Prednison zugelassen. Eine allogene Transplantation kann bei Patienten ohne relevante Komorbiditäten mit einer Hochrisikokonstellation oder mit Frührezidiv nach autologer Blutstammzelltransplantation erwogen werden, sollte jedoch nur innerhalb klinischer Studien und an spezialisierten Zentren erfolgen.

Schlüsselwörter

Autologe Blutstammzelltransplantation Allogene Blutstammzelltransplantation Lenalidomid Bortezomib Antikörper 

First-line treatment of multiple myeloma

Abstract

Within the last two decades the therapeutic options for newly diagnosed multiple myeloma have changed dramatically. The implementation of high-dose chemotherapy with melphalan and subsequent autologous blood stem cell transplantation initially led to prolonged survival in younger, fit patients. Furthermore, recent data suggest that patients with high-risk disease seem to benefit most from tandem transplantation approaches. Therefore, risk stratification at initiation of first-line treatment is of great importance. With the advent and integration of the so-called novel agents, such as thalidomide, lenalidomide and bortezomib into first-line treatment, both transplant eligible and ineligble patients gained new therapeutic perspectives. In Germany, the combination of bortezomib with cyclophosphamide and dexamethasone is currently considered the standard of care as induction regimen before high-dose treatment and transplantation; however, the combination of lenalidomide, bortezomib and dexamethasone is increasingly being used, but is still not yet approved in Germany. For patients where high-dose therapy and stem cell transplantation are not feasible, bortezomib and lenalidomide are available as backbone agents of various combination regimens. Recently, the anti-CD38 antibody daratumumab has been approved in combination with bortezomib, melphalan and prednisone as primary treatment for newly diagnosed patients. An allogeneic stem cell transplantation can be considered for younger patients without relevant comorbidities and with high-risk disease or early relapse after autologous blood stem cell transplantation but should only be performed within controlled clinical trials and in specialized centers.

Keywords

Autologous blood stem cell transplantation Allogeneic blood stem cell transplantation Lenalidomide Bortezomib Antibodies 

Notes

Einhaltung ethischer Richtlinien

Interessenkonflikt

I. Breitkreutz erhielt finanzielle Unterstützung von der Firma Celgene zum Besuch von Fortbildungsveranstaltungen. M. Raab erhielt Honorare, Reisekostenunterstützungen bzw. Forschungsmittel von Janssen, Celgene, BMS, Novartis, Sanofi, Takeda. H. Goldschmidt erhielt Honorare, Reisekostenunterstützungen und Forschungsmittel von Janssen, Celgene, BMS, Novartis, Sanofi.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

Literatur

  1. 1.
    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 (2003) Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med 349:2495–2502CrossRefGoogle Scholar
  2. 2.
    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. Intergroupe Francais du Myelome. N Engl J Med 335:91–97CrossRefGoogle Scholar
  3. 3.
    Attal M, Lauwers-Cances V, Hulin C, Leleu X, Caillot D, Escoffre M, Arnulf B, Macro M, Belhadj K, Garderet L, Roussel M, Payen C, Mathiot C, Fermand JP, Meuleman N, Rollet S, Maglio ME, Zeytoonjian AA, Weller EA, Munshi N, Anderson KC, Richardson PG, Facon T, Avet-Loiseau H, Harousseau JL, Moreau P (2017) Lenalidomide, Bortezomib, and Dexamethasone with transplantation for myeloma. N Engl J Med 376:1311–1320CrossRefGoogle Scholar
  4. 4.
    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
  5. 5.
    Bruno B, Rotta M, Patriarca F, Mordini N, Allione B, Carnevale-Schianca F, Giaccone L, Sorasio R, Omede P, Baldi I, Bringhen S, Massaia M, Aglietta M, Levis A, Gallamini A, Fanin R, Palumbo A, Storb R, Ciccone G, Boccadoro M (2007) A comparison of allografting with autografting for newly diagnosed myeloma. N Engl J Med 356:1110–1120CrossRefGoogle Scholar
  6. 6.
    Cavo M, Tacchetti P, Patriarca F, Petrucci MT, Pantani L, Galli M, Di Raimondo F, Crippa C, Zamagni E, Palumbo A, Offidani M, Corradini P, Narni F, Spadano A, Pescosta N, Deliliers GL, Ledda A, Cellini C, Caravita T, Tosi P, Baccarani M, Network GIM (2010) Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study. Lancet 376:2075–2085CrossRefGoogle Scholar
  7. 7.
    Dimopoulos MA, Oriol A, Nahi H, San-Miguel J, Bahlis NJ, Usmani SZ, Rabin N, Orlowski RZ, Komarnicki M, Suzuki K, Plesner T, Yoon SS, Ben Yehuda D, Richardson PG, Goldschmidt H, Reece D, Lisby S, Khokhar NZ, O’Rourke L, Chiu C, Qin X, Guckert M, Ahmadi T, Moreau P (2016) Daratumumab, Lenalidomide, and Dexamethasone for multiple myeloma. N Engl J Med 375:1319–1331CrossRefGoogle Scholar
  8. 8.
    Durie BG, Hoering A, Abidi MH, Rajkumar SV, Epstein J, Kahanic SP, Thakuri M, Reu F, Reynolds CM, Sexton R, Orlowski RZ, Barlogie B, Dispenzieri A (2017) Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial. Lancet 389:519–527CrossRefGoogle Scholar
  9. 9.
    Facon T, Dimopoulos MA, Dispenzieri A, Catalano JV, Belch A, Cavo M, Pinto A, Weisel K, Ludwig H, Bahlis NJ, Banos A, Tiab M, Delforge M, Cavenagh JD, Geraldes C, Lee JJ, Chen C, Oriol A, De la Rubia J, White D, Binder D, Lu J, Anderson KC, Moreau P, Attal M, Perrot A, Arnulf B, Qiu L, Roussel M, Boyle E, Manier S, Mohty M, Avet-Loiseau H, Leleu X, Ervin-Haynes A, Chen G, Houck V, Benboubker L, Hulin C (2018) Final analysis of survival outcomes in the phase 3 FIRST trial of up-front treatment for multiple myeloma. Blood 131:301–310CrossRefGoogle Scholar
  10. 10.
    Facon T, Mary JY, Hulin C, Benboubker L, Attal M, Pegourie B, Renaud M, Harousseau JL, Guillerm G, Chaleteix C, Dib M, Voillat L, Maisonneuve H, Troncy J, Dorvaux V, Monconduit M, Martin C, Casassus P, Jaubert J, Jardel H, Doyen C, Kolb B, Anglaret B, Grosbois B, Yakoub-Agha I, Mathiot C, vet-Loiseau H (2007) Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99-06): a randomised trial. Lancet 370:1209–1218CrossRefGoogle Scholar
  11. 11.
    Gahrton G, Tura S, Ljungman P, Belanger C, Brandt L, Cavo M, Facon T, Granena A, Gore M, Gratwohl A et al (1991) Allogeneic bone marrow transplantation in multiple myeloma. European Group for Bone Marrow Transplantation. N Engl J Med 325:1267–1273CrossRefGoogle Scholar
  12. 12.
    Gerull S, Goerner M, Benner A, Hegenbart U, Klein U, Schaefer H, Goldschmidt H, Ho AD (2005) Long-term outcome of nonmyeloablative allogeneic transplantation in patients with high-risk multiple myeloma. Bone Marrow Transplant 36:963–969CrossRefGoogle Scholar
  13. 13.
    Goldschmidt H, Lokhorst HM, Mai EK, van der Holt B, Blau IW, Zweegman S, Weisel KC, Vellenga E, Pfreundschuh M, Kersten MJ, Scheid C, Croockewit S, Raymakers R, Hose D, Potamianou A, Jauch A, Hillengass J, Stevens-Kroef M, Raab MS, Broijl A, Lindemann HW, Bos GMJ, Brossart P, van Marwijk Kooy M, Ypma P, Duehrsen U, Schaafsma RM, Bertsch U, Hielscher T, Jarari L, Salwender HJ, Sonneveld P (2017) Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMG-HD4 trial. Leukemia.  https://doi.org/10.1038/leu.2017.211 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Harousseau JL, Attal M, Avet-Loiseau H, Marit G, Caillot D, Mohty M, Lenain P, Hulin C, Facon T, Casassus P, Michallet M, Maisonneuve H, Benboubker L, Maloisel F, Petillon MO, Webb I, Mathiot C, Moreau P (2010) Bortezomib plus dexamethasone is superior to vincristine plus doxorubicin plus dexamethasone as induction treatment prior to autologous stem-cell transplantation in newly diagnosed multiple myeloma: results of the IFM 2005-01 phase III trial. J Clin Oncol 28:4621–4629CrossRefGoogle Scholar
  15. 15.
    Hulin C, Facon T, Rodon P, Pegourie B, Benboubker L, Doyen C, Dib M, Guillerm G, Salles B, Eschard JP, Lenain P, Casassus P, Azais I, Decaux O, Garderet L, Mathiot C, Fontan J, Lafon I, Virion JM, Moreau P (2009) Efficacy of melphalan and prednisone plus thalidomide in patients older than 75 years with newly diagnosed multiple myeloma: IFM 01/01 trial. J Clin Oncol 27:3664–3670CrossRefGoogle Scholar
  16. 16.
    Laubach J, Garderet L, Mahindra A, Gahrton G, Caers J, Sezer O, Voorhees P, Leleu X, Johnsen HE, Streetly M, Jurczyszyn A, Ludwig H, Mellqvist UH, Chng WJ, Pilarski L, Einsele H, Hou J, Turesson I, Zamagni E, Chim CS, Mazumder A, Westin J, Lu J, Reiman T, Kristinsson S, Joshua D, Roussel M, O’Gorman P, Terpos E, McCarthy P, Dimopoulos M, Moreau P, Orlowski RZ, Miguel JS, Anderson KC, Palumbo A, Kumar S, Rajkumar V, Durie B, Richardson PG (2016) Management of relapsed multiple myeloma: recommendations of the International Myeloma Working Group. Leukemia 30:1005–1017CrossRefGoogle Scholar
  17. 17.
    Lokhorst HM, Schmidt-Wolf I, Sonneveld P, van der Holt B, Martin H, Barge R, Bertsch U, Schlenzka J, Bos GM, Croockewit S, Zweegman S, Breitkreuz I, Joosten P, Scheid C, van Marwijk-Kooy M, Salwender HJ, van Oers MH, Schaafsma R, Naumann R, Sinnige H, Blau I, Verhoef G, de Weerdt O, Wijermans P, Wittebol S, Duersen U, Vellenga E, Goldschmidt H (2008) Thalidomide in induction treatment increases the very good partial response rate before and after high-dose therapy in previously untreated multiple myeloma. Haematologica 93:124–127CrossRefGoogle Scholar
  18. 18.
    Lokhorst HM, van der Holt B, Zweegman S, Vellenga E, Croockewit S, van Oers MH, von dem Borne P, Wijermans P, Schaafsma R, de Weerdt O, Wittebol S, Delforge M, Berenschot H, Bos GM, Jie KS, Sinnige H, van Marwijk-Kooy M, Joosten P, Minnema MC, van Ammerlaan R, Sonneveld P, Dutch-Belgian Hemato-Oncology G (2010) A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma. Blood 115:1113–1120CrossRefGoogle Scholar
  19. 19.
    Mai EK, Benner A, Bertsch U, Brossart P, Hanel A, Kunzmann V, Naumann R, Neben K, Egerer G, Ho AD, Hillengass J, Raab MS, Neubauer A, Peyn A, Ko YD, Peter N, Scheid C, Goldschmidt H (2016) Single versus tandem high-dose melphalan followed by autologous blood stem cell transplantation in multiple myeloma: long-term results from the phase III GMMG-HD2 trial. Br J Haematol 173:731–741CrossRefGoogle Scholar
  20. 20.
    Mateos MV, Dimopoulos MA, Cavo M, Suzuki K, Jakubowiak A, Knop S, Doyen C, Lucio P, Nagy Z, Kaplan P, Pour L, Cook M, Grosicki S, Crepaldi A, Liberati AM, Campbell P, Shelekhova T, Yoon SS, Iosava G, Fujisaki T, Garg M, Chiu C, Wang J, Carson R, Crist W, Deraedt W, Nguyen H, Qi M, San-Miguel J (2018) Daratumumab plus Bortezomib, Melphalan, and Prednisone for untreated myeloma. N Engl J Med 378:518–528CrossRefGoogle Scholar
  21. 21.
    Mateos MV, Oriol A, Martinez-Lopez J, Gutierrez N, Teruel AI, de Paz R, Garcia-Larana J, Bengoechea E, Martin A, Mediavilla JD, Palomera L, de Arriba F, Gonzalez Y, Hernandez JM, Sureda A, Bello JL, Bargay J, Penalver FJ, Ribera JM, Martin-Mateos ML, Garcia-Sanz R, Cibeira MT, Ramos ML, Vidriales MB, Paiva B, Montalban MA, Lahuerta JJ, Blade J, Miguel JF (2010) Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myeloma: a randomised trial. Lancet Oncol 11:934–941CrossRefGoogle Scholar
  22. 22.
    McCarthy PL, Holstein SA, Petrucci MT, Richardson PG, Hulin C, Tosi P, Bringhen S, Musto P, Anderson KC, Caillot D, Gay F, Moreau P, Marit G, Jung SH, Yu Z, Winograd B, Knight RD, Palumbo A, Attal M (2017) Lenalidomide maintenance after autologous stem-cell transplantation in newly diagnosed multiple myeloma: a meta-analysis. J Clin Oncol 35:3279–3289CrossRefGoogle Scholar
  23. 23.
    Moreau P, Garban F, Attal M, Michallet M, Marit G, Hulin C, Benboubker L, Doyen C, Mohty M, Yakoub-Agha I, Leyvraz S, Casassus P, Avet-Loiseau H, Garderet L, Mathiot C, Harousseau JL, Group IFM (2008) Long-term follow-up results of IFM99-03 and IFM99-04 trials comparing nonmyeloablative allotransplantation with autologous transplantation in high-risk de novo multiple myeloma. Blood 112:3914–3915CrossRefGoogle Scholar
  24. 24.
    Moreau P, Hulin C, Macro M, Caillot D, Chaleteix C, Roussel M, Garderet L, Royer B, Brechignac S, Tiab M, Puyade M, Escoffre M, Stoppa AM, Facon T, Pegourie B, Chaoui D, Jaccard A, Slama B, Marit G, Laribi K, Godmer P, Luycx O, Eisenmann JC, Allangba O, Dib M, Araujo C, Fontan J, Belhadj K, Wetterwald M, Dorvaux V, Fermand JP, Rodon P, Kolb B, Glaisner S, Malfuson JV, Lenain P, Biron L, Planche L, Caillon H, Avet-Loiseau H, Dejoie T, Attal M (2016) VTD is superior to VCD prior to intensive therapy in multiple myeloma: results of the prospective IFM2013-04 trial. Blood 127:2569–2574CrossRefGoogle Scholar
  25. 25.
    Palumbo A, Bringhen S, Liberati AM, Caravita T, Falcone A, Callea V, Montanaro M, Ria R, Capaldi A, Zambello R, Benevolo G, Derudas D, Dore F, Cavallo F, Gay F, Falco P, Ciccone G, Musto P, Cavo M, Boccadoro M (2008) Oral melphalan, prednisone, and thalidomide in elderly patients with multiple myeloma: updated results of a randomized controlled trial. Blood 112:3107–3114CrossRefGoogle Scholar
  26. 26.
    Palumbo A, Cavallo F, Gay F, Di Raimondo F, Ben Yehuda D, Petrucci MT, Pezzatti S, Caravita T, Cerrato C, Ribakovsky E, Genuardi M, Cafro A, Marcatti M, Catalano L, Offidani M, Carella AM, Zamagni E, Patriarca F, Musto P, Evangelista A, Ciccone G, Omede P, Crippa C, Corradini P, Nagler A, Boccadoro M, Cavo M (2014) Autologous transplantation and maintenance therapy in multiple myeloma. N Engl J Med 371:895–905CrossRefGoogle Scholar
  27. 27.
    Palumbo A, Chanan-Khan A, Weisel K, Nooka AK, Masszi T, Beksac M, Spicka I, Hungria V, Munder M, Mateos MV, Mark TM, Qi M, Schecter J, Amin H, Qin X, Deraedt W, Ahmadi T, Spencer A, Sonneveld P (2016) Daratumumab, Bortezomib, and Dexamethasone for multiple myeloma. N Engl J Med 375:754–766CrossRefGoogle Scholar
  28. 28.
    Palumbo A, Hajek R, Delforge M, Kropff M, Petrucci MT, Catalano J, Gisslinger H, Wiktor-Jedrzejczak W, Zodelava M, Weisel K, Cascavilla N, Iosava G, Cavo M, Kloczko J, Blade J, Beksac M, Spicka I, Plesner T, Radke J, Langer C, Ben Yehuda D, Corso A, Herbein L, Yu Z, Mei J, Jacques C, Dimopoulos MA, Investigators MM (2012) Continuous lenalidomide treatment for newly diagnosed multiple myeloma. N Engl J Med 366:1759–1769CrossRefGoogle Scholar
  29. 29.
    Rajkumar SV, Blood E, Vesole D, Fonseca R, Greipp PR (2006) Phase III clinical trial of thalidomide plus dexamethasone compared with dexamethasone alone in newly diagnosed multiple myeloma: a clinical trial coordinated by the Eastern Cooperative Oncology Group. J Clin Oncol 24:431–436CrossRefGoogle Scholar
  30. 30.
    Rajkumar SV, Jacobus S, Callander NS, Fonseca R, Vesole DH, Williams ME, Abonour R, Siegel DS, Katz M, Greipp PR, Eastern Cooperative Oncology G (2010) Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial. Lancet Oncol 11:29–37CrossRefGoogle Scholar
  31. 31.
    Richardson PG, Weller E, Lonial S, Jakubowiak AJ, Jagannath S, Raje NS, Avigan DE, Xie W, Ghobrial IM, Schlossman RL, Mazumder A, Munshi NC, Vesole DH, Joyce R, Kaufman JL, Doss D, Warren DL, Lunde LE, Kaster S, Delaney C, Hideshima T, Mitsiades CS, Knight R, Esseltine DL, Anderson KC (2010) Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood.  https://doi.org/10.1182/blood-2010-02-268862 CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Rosinol L, Perez-Simon JA, Sureda A, de la Rubia J, de Arriba F, Lahuerta JJ, Gonzalez JD, Diaz-Mediavilla J, Hernandez B, Garcia-Frade J, Carrera D, Leon A, Hernandez M, Abellan PF, Bergua JM, San Miguel J, Blade J, Programa para el Estudio y la Terapeutica de las Hemopatias Malignas y Grupo Espanol de M (2008) A prospective PETHEMA study of tandem autologous transplantation versus autograft followed by reduced-intensity conditioning allogeneic transplantation in newly diagnosed multiple myeloma. Blood 112:3591–3593CrossRefGoogle Scholar
  33. 33.
    Roussel M, Lauwers-Cances V, Robillard N, Hulin C, Leleu X, Benboubker L, Marit G, Moreau P, Pegourie B, Caillot D, Fruchart C, Stoppa AM, Gentil C, Wuilleme S, Huynh A, Hebraud B, Corre J, Chretien ML, Facon T, Avet-Loiseau H, Attal M (2014) Front-line transplantation program with lenalidomide, bortezomib, and dexamethasone combination as induction and consolidation followed by lenalidomide maintenance in patients with multiple myeloma: a phase II study by the Intergroupe Francophone du Myelome. J Clin Oncol 32:2712–2717CrossRefGoogle Scholar
  34. 34.
    San Miguel JF, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, Kropff M, Spicka I, Petrucci MT, Palumbo A, Samoilova OS, Dmoszynska A, Abdulkadyrov KM, Delforge M, Jiang B, Mateos MV, Anderson KC, Esseltine DL, Liu K, Deraedt W, Cakana A, van de Velde H, Richardson PG (2013) Persistent overall survival benefit and no increased risk of second malignancies with bortezomib-melphalan-prednisone versus melphalan-prednisone in patients with previously untreated multiple myeloma. J Clin Oncol 31:448–455CrossRefGoogle Scholar
  35. 35.
    San Miguel JF, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, Kropff M, Spicka I, Petrucci MT, Palumbo A, Samoilova OS, Dmoszynska A, Abdulkadyrov KM, Schots R, Jiang B, Mateos MV, Anderson KC, Esseltine DL, Liu K, Cakana A, van de Velde H, Richardson PG (2008) Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med 359:906–917CrossRefGoogle Scholar
  36. 36.
    Sonneveld P, Schmidt-Wolf IG, van der Holt B, El Jarari L, Bertsch U, Salwender H, Zweegman S, Vellenga E, Broyl A, Blau IW, Weisel KC, Wittebol S, Bos GM, Stevens-Kroef M, Scheid C, Pfreundschuh M, Hose D, Jauch A, van der Velde H, Raymakers R, Schaafsma MR, Kersten MJ, van Marwijk-Kooy M, Duehrsen U, Lindemann W, Wijermans PW, Lokhorst HM, Goldschmidt HM (2012) Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/ GMMG-HD4 trial. J Clin Oncol 30:2946–2955CrossRefGoogle Scholar
  37. 37.
    Testoni N, Marzocchi G, Pantani L, Ameli G, Dozza L, Gay F, Petrucci MT, Di Raimondo F, Patriarca F, Galli M, Montefusco V, Gamberi B, Crippa C, Vincelli DI, Offidani M, Terragna C, Mancuso K, Rocchi S, Sonneveld P, Boccadoro M, Cavo M (2017) High-risk cytogenetics in newly diagnosed multiple myeloma: prognostic relevance of co-segregations and analysis of the role of double versus single autotransplantation. Blood 130:394–394Google Scholar

Copyright information

© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2018

Authors and Affiliations

  1. 1.Medizinische Klinik VUniversitätsklinikum HeidelbergHeidelbergDeutschland

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