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Plasma Cell Disorders

Impact of CR before and after allogeneic and autologous transplantation in multiple myeloma: results from the EBMT NMAM2000 prospective trial

Bone Marrow Transplantation volume 50, pages 505–510 (2015)Cite this article

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Abstract

Previous studies have shown that obtaining complete hematologic remission (CR) in multiple myeloma is an important predictor of PFS and OS. This applies both to autologous and allogeneic transplantation. However, the importance of CR obtained before vs after second transplant or following allogeneic vs autologous transplantation is not clear. We investigated the role of CR analyzing data from the EBMT-NMAM2000 interventional prospective study comparing tandem autologous/reduced intensity conditioning allogeneic transplantation (auto/RICallo) to autologous transplantation—single or double (auto/auto). Allocation to treatment was performed according to availability of a matched sibling donor. Cox regression and multi-state models were applied. The long-term probability of survival in CR was superior in auto/RICallo, both comparing groups according to treatment allocated at start (28.8 vs 11.4% at 60 months, P=0.0004) and according to actual administration of second transplant (25.6 vs 9.6% at 60 months, P=0.008). CR achieved before the second transplant was predictive for PFS (hazard ratio (HR)=0.44, P= 0.003) and OS (HR 0.51, P=0.047) irrespective of the type of second transplant. CR achieved after auto/RICallo was more beneficial for PFS (HR=0.53, P=0.027) than CR after auto/auto (HR=0.81, P=0.390), indicating a better durability of CR obtained after an allotransplant procedure.

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Acknowledgements

We would like to thank Hein Putter (Department of Medical Statistics and Bioinformatics, Leiden University Medical Center) for statistical input and for support through his grant awarded by the Netherlands Organization for Scientific Research (Grant ZONMW-912-07-018 ‘Prognostic modeling and dynamic prediction for competing risks and multi-state models’, LCdW). Other funding (GG): Swedish Cancer Fund; Stockholm Cancer Society; Netherlands Organization for Scientific Research. The funding sources had no role in the design and conduction of the study, nor in interpretation of the data or in decisions regarding writing the report and submitting for publication.

Author Contributions

Conception and design: SI, GG and DN. Collection and assembly of data: All authors. Data analysis and interpretation: SI, LCdW, SS, CM, DN, LG, NK and GG. Manuscript writing: All authors. Final approval of manuscript: All authors.

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Authors and Affiliations

  1. Centro Interdipartimentale di Biostatistica e Bioinformatica, Università di Roma ‘Tor Vergata’, Rome, Italy

    S Iacobelli

  2. Department of Biostatistics and Bioinformatic, Leiden University Medical Center, Leiden, The Netherlands

    L C de Wreede & A van Biezen

  3. Department of Medicine V, University Hospital of Heidelberg, Heidelberg, Germany

    S Schönland, U Hegenbart & H Goldschmidt

  4. Hematology Center/Huddinge, Karolinska University Hospital, Stockholm, Sweden

    B Björkstrand

  5. Department of Medicine, Karolinska Institute at Huddinge and Solna, Stockholm, Sweden

    A Gruber, K Friberg & G Gahrton

  6. Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria

    H Greinix

  7. Helsinki University Central Hospital, Comprehensive Cancer Center, Stem Cell Transplantation Unit, Helsinki, Finland

    L Volin

  8. Department of Oncology Hematology & Respiratory Diseases, AOU Policlinico Modena, University of Modena, Modena, Italy

    F Narni

  9. Department of Hematology and Stem Cell Transplant Unit, CSS Hospital IRCCS, S.G. Rotondo, Italy

    A M Carella

  10. Department of Hematology, Ankara University Faculty of Medicine, Ankara, Turkey

    M Beksac

  11. Department of Haematology, University of Florence, Careggi Hospital, Florence, Italy

    A Bosi

  12. Department of Haematology, Ospedale Ferrarotto, Catania, Italy

    G Milone

  13. Fondazione IRCCS Istituto Nazionale dei Tumori, University of Milano, Milano, Italy

    P Corradini

  14. Department of Tumor Immunology, Nijmegen Institute of Life Sciences, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

    T de Witte

  15. Department of Haematology, The Queens University, Belfast, UK

    C Morris

  16. Division of Hematology and Medical Oncology, University Hospital Leipzig, Leipzig, Germany

    D Niederwieser

  17. Département d'hématologie et de thérapie cellulaire, Hopital St Antoine, Paris, France

    L Garderet

  18. Department of Stem Cell Transplantation, University Hospital Hamburg-Eppendorf, Hamburg, Germany

    N Kröger

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  1. S Iacobelli
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  2. L C de Wreede
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  23. G Gahrton
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for the EBMT CMWP, Plasma Cell Disorders Subcommittee

Corresponding author

Correspondence to S Iacobelli.

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Competing interests

UH: Janssen and Binding Site—received personal fees outside the submitted work. SS: Janssen, Celgene and Binding Site– received personal fees outside the submitted work. PC: Celgene—Honoraria. HG: Janssen—advisory board, speakers bureau, research support; Celgene—advisory board, speakers bureau, research support; Novartis—advisory board, speakers bureau, research support; Chugai—speakers bureau, research support; Onyx—advisory board, speakers bureau; Millenium—advisory board, speakers bureau. GG: Fujimoto Pharmaceutical Cooperation Japan—consultant or advisory relationship; Celgene—Honoraria, research funding. The other authors have no conflicts of interest.

Additional information

This work has been presented at the 39th annual meeting of the European society for Blood and Marrow Transplantation, London, April 2013, oral session ‘CLL, MPD, MDS & Myeloma’, and it was presented as deliverable of the WP14 Stem Cell Transplant of European LeukemiaNet (February 2014).

Supplementary Information accompanies this paper on Bone Marrow Transplantation website

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Iacobelli, S., de Wreede, L., Schönland, S. et al. Impact of CR before and after allogeneic and autologous transplantation in multiple myeloma: results from the EBMT NMAM2000 prospective trial. Bone Marrow Transplant 50, 505–510 (2015). https://doi.org/10.1038/bmt.2014.310

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