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Lenalidomide, adriamycin, dexamethasone for induction followed by stem-cell transplant in newly diagnosed myeloma

Leukemia volume 31, pages 1816–1819 (2017)Cite this article

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High-dose chemotherapy plus autologous (auto) stem-cell transplantation (SCT) is a standard of care for patients aged below 65 years with newly diagnosed multiple myeloma (NDMM). It is possible that autoSCT followed by allogeneic SCT (alloSCT) may confer greater disease control than tandem autoSCT, as a result of the graft-versus-myeloma effect;1 however, clinical trials have produced conflicting results2, 3, 4, 5, 6, 7 and, despite the replacement of myeloablative by reduced-intensity conditioning, treatment-related mortality rates remain even higher with auto-alloSCT than with tandem autoSCT.8

The introduction of newer agents, such as the proteasome inhibitor bortezomib and the immunomodulatory drug thalidomide and its derivatives (IMiDs), has resulted in superior outcomes, and triple induction combinations incorporating at least one novel agent are now recommended in NDMM.9 IMiDs have been shown to bind to CRBN, thereby competitively inhibiting its chaperone function for CD147 and MCT1 proteins, and simultaneously enabling CRBN to target the lymphoid transcription factors IKZF1 and IKZF3 for ubiquitylation and proteasomal degradation.10, 11, 12 We recently analyzed the potential prognostic impact of levels of expression of CRBN, IKZF1, IKZF3 and BSG in bone marrow samples obtained from 60 patients with NDMM prior to SCT.13 For the first time, we were able to demonstrate a significant association between IKZF1 expression and treatment outcomes, with patients with low levels of IKZF1 expression faring exceptionally well with respect to both progression-free survival (PFS) and overall survival (OS).

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Acknowledgements

We thank all patients and families involved in the trial reported. Financial support for the trial was provided by Wilhelm Sander-Stiftung; grant number 2013.900.1. Medical writing support was provided by Sandralee Lewis, PhD, of the Investigator Initiated Research Writing Group (an initiative from Ashfield Healthcare Communications, part of UDG Healthcare plc) and was funded by Celgene Corporation. The trial was supported by financial grants from Celgene Germany GmbH, Amgen Germany GmbH and medac GmbH.

Author contributions

SK, HE and RCB were responsible for the conception and design of the study. ME, CL, AR, WR, BH, AK, CR and HB provided study materials or patients. SK, CL, L-OM, WR, FB, BH, AK, CR, HO, KS-E, MR, AG, CJ, HB, MS and AL collected and assembled the data. SK, CL, ME, BH, CR, SH, HE and RCB analyzed and interpreted the data. SK wrote the first draft of the manuscript. All the authors critically reviewed the manuscript and approved the final draft.

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The authors were fully responsible for all content and editorial decisions during the development of this manuscript, and approved the final version.

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Authors and Affiliations

  1. Division of Hematology and Medical Oncology, Würzburg University Medical Center, Würzburg, Germany

    S Knop, M Schreder, H Einsele & R C Bargou

  2. Department of Internal Medicine III, University of Ulm, Ulm, Germany

    C Langer

  3. Department of Hematology and Oncology, University of Freiburg Medical Center, Freiburg, Germany

    M Engelhardt

  4. Hematology and Oncology, Jena University Hospital, Jena, Germany

    L-O Mügge

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

    A Reichle

  6. Hematology and Oncology, Erlangen University Hospital, Erlangen, Germany

    W Rösler

  7. Department of Hematology and Oncology, University Hospital Rechts der Isar, Munich, Germany

    F Bassermann

  8. Hematology and Oncology, Bremen-Mitte Clinic, Bremen, Germany

    B Hertenstein

  9. Hematology and Oncology, Charité Campus Virchow, Berlin, Germany

    A Kunitz

  10. Department of Internal Medicine I, University Hospital Carl Gustav Carus Dresden, Dresden, Germany

    C Röllig

  11. Department of Hematology, University Hospital Großhadern, Munich, Germany

    H Ostermann

  12. Medical Center, Nürnberg Nord Hospital, Nürnberg, Germany

    K Schäfer-Eckart

  13. Third Department of Medicine, Karlsruhe Hospital, Karlsruhe, Germany

    M Ringhoffer

  14. Second Department of Medicine, Division of Stem Cell Transplantation and Immunotherapy, University of Kiel, Kiel, Germany

    A Günther

  15. Department of Medicine, Clinic III (Hematology/Oncology/Palliative Care), University Medical Center, Rostock, Germany

    C Junghanss

  16. Hematology and Oncology, Schleswig-Holstein University Hospital, Lübeck, Germany

    H Biersack

  17. ClinAssess GmbH, Leverkusen, Germany

    A Liebert & S Held

Authors
  1. S Knop
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  20. H Einsele
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for the Deutsche Studiengruppe Multiples Myelom (DSMM)

Corresponding author

Correspondence to S Knop.

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Competing interests

Stock ownership: WR, Amgen, Immunomedics. Honoraria: SK, Celgene Germany, Amgen Germany, BMS Germany, ONYX Inc., Janssen Germany; ME, Celgene, Janssen, MSD, Amgen; L-OM, Celgene, Janssen-Cilag, Novartis; FB, Celgene; MR, Celgene; AG, Novartis, Celgene, Janssen; MS, Novartis; HE, Janssen, Amgen, Novartis, Celgene; RCB, Amgen, Novartis, GeoMab. Consultant or advisory role: SK, Celgene Germany, Amgen Germany, Celgene Inc.; CL, Celgene, Janssen, Amgen, Novartis, Takeda, BMS; ME, Celgene, Janssen, MSD, Amgen; WR, Janssen, MSD; FB, Celgene; BH, Amgen; CR, Amgen, BMS, Celgene, Janssen, Roche, Takeda; HO, MSD, Gilead, AstraZeneca, Teva; AG, Novartis, Takeda; HB, BMS, Roche, Pfizer, MSD, Sanofi; HE, Janssen, Celgene, Amgen; RCB, Amgen, Novartis, GeoMab. Speakers’ bureau: CR, Amgen, BMS, Celgene, Janssen, Roche, Takeda; HO, MSD, AstraZeneca, Novartis, Teva; HE, Janssen, Celgene, Novartis. Research funding: L-OM, Celgene; FB, Celgene; CR, Bayer; HO, MSD, Genzyme, Cereus; HE, Amgen, Celgene, Janssen. Patents, royalties, other intellectual property: RCB, Amgen. Travel, accommodation, expenses: CL, Celgene, Takeda, BMS; ME, Celgene, Janssen, MSD, Amgen; L-OM, Novartis, Celgene; WR, medac, Janssen, MSD; FB, Celgene, BMS; BH, Teva, Amgen, Novartis, Neovi; CR, Amgen, Celgene, Janssen, Gilead; HO, MSD, Gilead, AstraZeneca; MR, medac; HB, Jazz, Eusapharma, Sanofi, Amgen; MS, Celgene; RCB, Amgen, Novartis, GeoMab. The remaining authors declare no conflict of interest.

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Knop, S., Langer, C., Engelhardt, M. et al. Lenalidomide, adriamycin, dexamethasone for induction followed by stem-cell transplant in newly diagnosed myeloma. Leukemia 31, 1816–1819 (2017). https://doi.org/10.1038/leu.2017.124

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