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Multiple myeloma gammopathies

Allogeneic transplantation in multiple myeloma: long-term follow-up and cytogenetic subgroup analysis

Leukemia volume 33, pages 2710–2719 (2019)Cite this article

Subjects

Abstract

This phase 3 trial compared tandem autologous stem cell transplantation (autoSCT) versus autoSCT followed by reduced-intensity conditioning allogeneic stem cell transplantation (auto/alloSCT) in patients with newly diagnosed multiple myeloma (MM) with deletion of (del) chromosome 13q (del13q). The availability/absence of a human leukocyte antigen-matched-related or matched-unrelated donor (MUD) determined the nature of the second SCT. The primary endpoint was progression-free survival (PFS) in the intention-to-treat population (n = 199). Auto/alloSCT was performed in 126 patients; 74 received MUD allografts. After 91 months median follow-up, median PFS with auto/allo versus tandem autoSCT was 34.5 versus 21.8 months (P = 0.003; adjusted hazard ratio 0.55, 95% confidence interval 0.36–0.84). Median overall survival (OS) was 70.2 versus 71.8 months (P = 0.856). Two-year non-relapse mortality with auto/allo versus tandem autoSCT was 14.3% versus 4.1% (P = 0.008). In patients harboring both del13q and del17p, median PFS and OS were 37.5 and 61.5 months with auto/allo (n = 19) versus 6.1 and 23.4 months with tandem autoSCT (n = 6) (P = 0.0002 and 0.032). Our findings suggest that auto/alloSCT significantly extends PFS versus tandem autoSCT in del13q MM, and indicate some survival benefit for first-line alloSCT in high-risk MM.

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Acknowledgements

We would like to thank the patients who consented to participate, their families and caregivers, and the study nurses in the DSMM centers. We are indebted to Martina Haase, Lisa Hubert, Annette Nobis, and Verena Pscheidl for their help in putting long-term follow-up data together, and to Sandralee Lewis, PhD, working on behalf of the Investigator Initiated Research Writing Group (an initiative from Ashfield Healthcare Communications, part of UDG Healthcare plc), for medical writing support (funded by Würzburg University Medical Center). The trial was sponsored by Würzburg University, Würzburg, Germany.

Investigators of the German Myeloma Study Group DSMM (Deutsche Studiengruppe Multiples Myelom) are as follows:

O. Sezer30, B. Dörken30, C. Gerecke31, S. Fuhrmann31, W. D. Ludwig31, B. Hertenstein32, M. Bormann32, R. Meyer33, R. Naumann34, U. Platzbecker34, Ch. Röllig34, W. Rösler35, I. von Metzler36, H. Martin36, M. Engelhardt37, J. Finke37, L. Trümper38, W. Jung38, Ch. A. Schmidt39, G. Dölken39, H. H. Wolf40, L. Müller40, K. Ligeti40, N. Kröger41, G. Schilling41, H. Dürk42, D. Peest43, A. Ganser43, M. Pfreundschuh44, H. Sayer45, M. von Lilienfeld-Toal45, L. O. Mügge45, M. Bentz46, M. Gramatzki47, M. Brüggemann47, T. Fischer48, D. Wolleschak10, G. Hess49, M. Kropff50, J. Reusch50, C. Straka51, H. Ostermann52, D. Franke52, C. Peschel53, T. Dechow53, F. Bassermann53, M. Hentrich54, H. Wandt55, K. Schäfer-Eckart55, B. Metzner56, G. Maschmeyer57, E. Holler58, C. Hart58, A. Reichle58, M. Freund59, S. Böttcher59, C. Kahl59, H. G. Mergenthaler60, W. Aulitzky61, M. Kaufmann61, J. Greiner62, E. Heidemann62, L. Kanz63, H. Hebart63, P. Liebisch3, D. Bunjes3, C. Langer3, N. Frickhofen64, H. Einsele1, S. Knop1, S. Mielke1, R. C. Bargou1, M. Svaldi65

Author information

Author notes

  1. Deceased: M. Pfreundschuh

  2. Deceased: E. Heidemann

Authors and Affiliations

  1. Department of Internal Medicine II, Division of Hematology and Medical Oncology, Würzburg University Medical Centre, Würzburg, Germany

    Stefan Knop, Stephan Mielke, Hermann Einsele, H. Einsele, S. Knop, S. Mielke & R. C. Bargou

  2. Department of Hematology, Oncology and Stem Cell Transplantation, University Medical Centre, Freiburg, Germany

    Monika Engelhardt

  3. Klinik für Innere Medizin III, Ulm University Hospital, Ulm, Germany

    Peter Liebisch, Donald Bunjes, Christian H. Langer, P. Liebisch, D. Bunjes & C. Langer

  4. Institute for Clinical Epidemiology and Applied Biometry, Tübingen University Medical School, Tübingen, Germany

    Christoph Meisner

  5. Department of Hematology and Oncology, University of Regensburg, Regensburg, Germany

    Ernst Holler

  6. University Clinic for Internal Medicine – Oncology and Haematology, Oldenburg, Germany

    Bernd Metzner

  7. Department of Hematology, Oncology and Haemostaseology, Hanover Medical School, Hanover, Germany

    Dietrich Peest

  8. Medical Centre, Robert-Bosch-Hospital, Stuttgart, Germany

    Martin Kaufmann

  9. Hematology, Oncology and Infectiology, Munich Schwabing Hospital, Munich, Germany

    Christian Straka

  10. Department of Hematology and Oncology, Centre of Internal Medicine, Otto-von-Guericke University, Magdeburg, Germany

    Thomas Fischer & D. Wolleschak

  11. Department of Hematology/Oncology, Charite – Oncology Centre, Berlin, Germany

    Orhan Sezer

  12. Hematology and Oncology, Red Cross Hospital, Munich, Germany

    Marcus Hentrich

  13. Department of Hematology, University Hospital Grosshadern, Munich, Germany

    Helmut Ostermann

  14. IIIrd Department of Internal Medicine, Hematology/Oncology, Technical University, Munich, Germany

    Florian Bassermann

  15. Department of Hematology, Oncology and Pneumology, Universitätsmedizin Mainz, Mainz, Germany

    Georg Hess

  16. Department of Internal Medicine I, Klinikum Bremen Mitte, Bremen, Germany

    Bernd Hertenstein

  17. Hematology, Oncology, Palliative Medicine, University of Rostock, Rostock, Germany

    Mathias Freund

  18. Hematology and Oncology, University of Munster, Munster, Germany

    Martin Kropff

  19. Department of Internal Medicine, Greifswald University Hospital, Greifswald, Germany

    Christian A. Schmidt

  20. Department of Hematology and Oncology, University Hospital, Halle, Germany

    Hans-Heinrich Wolf

  21. Hematology and Oncology, Zentrum Innere Medizin, Gottingen, Germany

    Wolfram Jung

  22. Hematology/Oncology, HSK, Dr. Horst-Schmidt-Klinik, Wiesbaden, Germany

    Norbert Frickhofen

  23. Department of Laboratory Medicine, CAST, Karolinska Institutet and University Hospital, Stockholm, Sweden

    Stephan Mielke

  24. Department of Hematology and Oncology, Charité University Hospital, Berlin, Germany

    Ralf C. Bargou

  25. Department of Hematology, Oncology and Palliative Care, Ernst von Bergmann Hospital, Potsdam, Germany

    Georg Maschmeyer

  26. Bolzano Municipal Hospital, Bolzano, Italy

    Mirija Svaldi

  27. Department of Stem Cell Transplantation and Immunotherapy, Schleswig-Holstein University Hospital, Kiel Campus, Kiel, Germany

    Martin Gramatzki

  28. Department of Internal Medicine, Stauferklinikum Schwäbisch Gmünd, Mutlangen, Germany

    Holger Hebart

  29. Department for Oncology, Hematology, Immunology, Rheumatology and Pneumology, University Hospital, Tübingen, Germany

    Lothar Kanz

  30. Charité University Hospital, Berlin, Germany

    O. Sezer & B. Dörken

  31. HELIOS Klinikum, Berlin, Germany

    C. Gerecke, S Fuhrmann & W. D Ludwig

  32. Klinikum Bremen Mitte, Bremen, Germany

    B. Hertenstein & M. Bormann

  33. St. Johannes Hospital, Dortmund, Germany

    R. Meyer

  34. University Hospital, Dresden, Germany

    R. Naumann, U. Platzbecker & Ch. Röllig

  35. University Hospital, Erlangen, Germany

    W. Rösler

  36. University Hospital, Frankfurt, Germany

    I. von Metzler & H. Martin

  37. University Hospital, Freiburg, Germany

    M. Engelhardt & J. Finke

  38. University Hospital, Göttingen, Germany

    L. Trümper & W. Jung

  39. University Hospital, Greifswald, Germany

    Ch. A. Schmidt & G. Dölken

  40. University Hospital, Halle/Saale, Germany

    H. H. Wolf, L. Müller & K. Ligeti

  41. University Hospital, Hamburg, Germany

    N. Kröger & G. Schilling

  42. St. Marien-Hospital, Hamm, Germany

    H. Dürk

  43. Medical School, Hanover, Germany

    D. Peest & A. Ganser

  44. University Hospital, Homburg, Germany

    M. Pfreundschuh

  45. University Hospital, Jena, Germany

    H. Sayer, M. von Lilienfeld-Toal & L. O. Mügge

  46. Municipal Hospital, Karlsruhe, Germany

    M. Bentz

  47. University Hospital, Kiel, Germany

    M. Gramatzki & M. Brüggemann

  48. Department of Internal Medicine II, Division of Hematology and Medical Oncology, Magdeburg, Germany

    T. Fischer

  49. University Hospital, Mainz, Germany

    G. Hess

  50. University Hospital, Munster, Germany

    M. Kropff & J. Reusch

  51. Innenstadtklinikum, Munich, Germany

    C. Straka

  52. Grosshadern University Hospital, Munich, Germany

    H. Ostermann & D. Franke

  53. University Hospital rechts der Isar, Munich, Germany

    C. Peschel, T. Dechow & F. Bassermann

  54. Red Cross Hospital, Munich, Germany

    M. Hentrich

  55. Klinikum Nord, Nuremberg, Germany

    H. Wandt & K. Schäfer-Eckart

  56. Klinikum, Oldenburg, Germany

    B. Metzner

  57. E.v.Bergmann Klinikum, Potsdam, Germany

    G. Maschmeyer

  58. University Hospital, Regensburg, Germany

    E. Holler, C. Hart & A. Reichle

  59. University Hospital, Rostock, Germany

    M. Freund, S. Böttcher & C. Kahl

  60. Klinium Stuttgart, Stuttgart, Germany

    H. G. Mergenthaler

  61. Robert-Bosch-Krankenhaus, Stuttgart, Germany

    W. Aulitzky & M. Kaufmann

  62. Diakonissenkrankenhaus, Stuttgart, Germany

    J. Greiner & E. Heidemann

  63. University Hospital, Tübingen, Germany

    L. Kanz & H. Hebart

  64. HELIOS Hospital, Wiesbaden, Germany

    N. Frickhofen

  65. Central Hospital, Bolzano, Italy

    M. Svaldi

Authors
  1. Stefan Knop
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  2. Monika Engelhardt
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  3. Peter Liebisch
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  4. Christoph Meisner
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  5. Ernst Holler
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  6. Bernd Metzner
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  7. Dietrich Peest
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  8. Martin Kaufmann
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  9. Donald Bunjes
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  10. Christian Straka
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  11. Thomas Fischer
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  12. Orhan Sezer
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  13. Marcus Hentrich
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  14. Helmut Ostermann
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  15. Florian Bassermann
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  16. Georg Hess
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  17. Bernd Hertenstein
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  18. Mathias Freund
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  19. Martin Kropff
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  20. Christian A. Schmidt
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  21. Hans-Heinrich Wolf
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  22. Wolfram Jung
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  23. Norbert Frickhofen
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  24. Stephan Mielke
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  25. Ralf C. Bargou
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  26. Georg Maschmeyer
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  27. Mirija Svaldi
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  28. Christian H. Langer
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  29. Martin Gramatzki
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  30. Holger Hebart
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  31. Lothar Kanz
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  32. Hermann Einsele
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Consortia

on behalf of Deutsche Studiengruppe Multiples Myelom

  • O. Sezer
  • , B. Dörken
  • , C. Gerecke
  • , S Fuhrmann
  • , W. D Ludwig
  • , B. Hertenstein
  • , M. Bormann
  • , R. Meyer
  • , R. Naumann
  • , U. Platzbecker
  • , Ch. Röllig
  • , W. Rösler
  • , I. von Metzler
  • , H. Martin
  • , M. Engelhardt
  • , J. Finke
  • , L. Trümper
  • , W. Jung
  • , Ch. A. Schmidt
  • , G. Dölken
  • , H. H. Wolf
  • , L. Müller
  • , K. Ligeti
  • , N. Kröger
  • , G. Schilling
  • , H. Dürk
  • , D. Peest
  • , A. Ganser
  • , M. Pfreundschuh
  • , H. Sayer
  • , M. von Lilienfeld-Toal
  • , L. O. Mügge
  • , M. Bentz
  • , M. Gramatzki
  • , M. Brüggemann
  • , T. Fischer
  • , D. Wolleschak
  • , G. Hess
  • , M. Kropff
  • , J. Reusch
  • , C. Straka
  • , H. Ostermann
  • , D. Franke
  • , C. Peschel
  • , T. Dechow
  • , F. Bassermann
  • , M. Hentrich
  • , H. Wandt
  • , K. Schäfer-Eckart
  • , B. Metzner
  • , G. Maschmeyer
  • , E. Holler
  • , C. Hart
  • , A. Reichle
  • , M. Freund
  • , S. Böttcher
  • , C. Kahl
  • , H. G. Mergenthaler
  • , W. Aulitzky
  • , M. Kaufmann
  • , J. Greiner
  • , E. Heidemann
  • , L. Kanz
  • , H. Hebart
  • , P. Liebisch
  • , D. Bunjes
  • , C. Langer
  • , N. Frickhofen
  • , H. Einsele
  • , S. Knop
  • , S. Mielke
  • , R. C. Bargou
  •  & M. Svaldi

Contributions

CM, CS, HH, and HE conceived and designed the work that led to the submission. SK, ME, PL, EH, BM, DP, MK, CAS, DB, TF, OS, MH, HO, FB, GH, BH, MF, MK, H-HW, WJ, NF, SM, RCB, GM, MS, CHL, MG, HH, LK, and HE acquired data and played an important role in interpreting the results. SK, ME, CM, and HE drafted the manuscript. PL, EH, BM, DP, MK, DB, CS, TF, OS, MH, HO, FB, GH, BH, MF, MK, CAS, H-HW, WJ, NF, SM, RCB, GM, MS, CHL, MG, HH, and LK revised the manuscript. CM conducted all the reported statistical analyses. All the authors approved the final version of the manuscript and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Corresponding author

Correspondence to Hermann Einsele.

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MH reports personal fees from Amgen, Celgene, Janssen, Bristol-Myers Squibb, and Takeda. GH reports personal fees from Janssen, Roche, AbbVie, Gilead, Novartis, MorphoSys, and Celgene; and grants from Roche, Pfizer, and Celgene. SM reports non-financial support from EBMT/EHA, IACH, Celgene, Miltenyi, KIADIS, Bellicum, DGHO, Jazz Pharma, and ISCT; and personal fees from Celgene, Miltenyi, KIADIS, Bellicum, and Jazz Pharma. GM reports personal fees from Gilead, Pfizer, Boehringer Ingelheim, Bristol-Myers Squibb, and Merck-Serono; and non-financial support from Janssen-Cilag. LK reports honoraria for presentation at “MedIpdate” (OnkoUpdate, IntemistenUpdate, PraxisUpdate) and at “Medizin Aktuell”. Amgen and Celgene are sponsors of the “Biannual International Stem Cell Conference, Tübingen, Germany): Scientific chairman: LK. HE reports grants, personal fees, and other (advisory board) from Janssen, Celgene, Amgen, Bristol-Myers Squibb, Novartis, and Takeda. The other authors declare that they have no conflict of interest.

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Investigators of the German Myeloma Study Group DSMM (Deutsche Studiengruppe Multiples Myelom) are listed at the end of the paper.

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Knop, S., Engelhardt, M., Liebisch, P. et al. Allogeneic transplantation in multiple myeloma: long-term follow-up and cytogenetic subgroup analysis. Leukemia 33, 2710–2719 (2019). https://doi.org/10.1038/s41375-019-0537-2

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