Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Upfront stem cell transplantation for newly diagnosed multiple myeloma with del(17p) and t(4;14): a study from the CMWP-EBMT

Bone Marrow Transplantation volume 56, pages 210–217 (2021)Cite this article

Subjects

Abstract

We analyzed newly diagnosed multiple myeloma patients with del(17p) and/or t(4;14) undergoing either upfront single autologous (auto), tandem autologous (auto-auto) or tandem autologous/reduced-intensity allogeneic (auto-allo) stem cell transplantation. 623 patients underwent either auto (n = 446), auto-auto (n = 105), or auto-allo (n = 72) between 2000 and 2015. 46% of patients had t(4;14), 45% had del(17p) while 9% were reported having both abnormalities. Five-year overall survival (OS) was 51% (95% confidence interval [CI], 45–58%) for single auto, 60% (95% CI, 49–72%) for auto-auto, and 67% (95% CI, 53–80%) for auto-allo (p = 0.187). Five-year progression-free survival (PFS) was 17% (95% CI, 12–22%), 33% (95% CI, 22–43%), and 34% (95% CI, 21–38%; p = 0.048). Five-year relapse rate was 82, 63, and 56%, while non-relapse mortality was 1, 4, and 10%. In multivariable analysis, in t(4;14) with single auto as reference, auto-auto (hazard ratio [HR], 0.44; p = 0.007) and auto-allo (HR, 0.45; p = 0.018) were associated with better PFS. In terms of t(4;14) and OS, auto-auto appeared to improve outcome compared with single auto (HR, 0.49; p = 0.096). In del(17p), outcome in PFS was similar between single auto and auto-auto, while auto-allo appeared to improve PFS (HR, 0.65; p = 0.097). No significant difference in OS was identified between the groups in patients with del(17p).

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Outcome according transplant strategy.
Fig. 2: Landmark overall survival of different transplant strategies in del(17p) (a) or t(4;14) (b).
Fig. 3: Landmark progression-free survival of different transplant strategies in del(17p) (a) or t(4;14) (b).

Similar content being viewed by others

References

  1. Moreau P, San Miguel J, Sonneveld P, Mateos MV, Zamagni E, Avet-Loiseau H, et al. Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28(suppl_4):iv52–iv61.

    Article  CAS  Google Scholar 

  2. Palumbo A, Anderson K. Multiple myeloma. N. Engl J Med. 2011;364:1046–60.

    Article  CAS  Google Scholar 

  3. Bergsagel PL, Mateos MV, Gutierrez NC, Rajkumar SV, San Miguel JF. Improving overall survival and overcoming adverse prognosis in the treatment of cytogenetically high-risk multiple myeloma. Blood. 2013;121:884–92.

    Article  CAS  Google Scholar 

  4. Sonneveld P, Avet-Loiseau H, Lonial S, Usmani S, Siegel D, Anderson KC, et al. Treatment of multiple myeloma with high-risk cytogenetics: a consensus of the International Myeloma Working Group. Blood. 2016;127:2955–62.

    Article  CAS  Google Scholar 

  5. Fonseca R, Bergsagel PL, Drach J, Shaughnessy J, Gutierrez N, Stewart AK, et al. International Myeloma Working Group molecular classification of multiple myeloma: spotlight review. Leukemia. 2009;23:2210–21.

    Article  CAS  Google Scholar 

  6. Robinson D, Kaura S, Kiely D, Hussein MA, Nersesyan K, Durie BG. Impact of novel treatments on multiple myeloma survival. Blood. 2014;124:5676.

    Article  Google Scholar 

  7. Joseph NS, Kaufman JL, Dhodapkar MV, Hofmeister CC, Almaula DK, Heffner LT, et al. Long-term follow-up results of lenalidomide, bortezomib, and dexamethasone induction therapy and risk-adapted maintenance approach in newly diagnosed multiple myeloma. J Clin Oncol. 2020; https://doi.org/10.1200/JCO.19.02515.

  8. Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF, et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma: Intergroupe Français du Myélome. N. Engl J Med. 1996;335:91–7.

    Article  CAS  Google Scholar 

  9. Moreau P, Attal M, Hulin C, Arnulf B, Belhadj K, Benboubker L, et al. Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study. Lancet. 2019;394:29–38.

    Article  CAS  Google Scholar 

  10. Barlogie B, Jagannath S, Vesole DH, Naucke S, Cheson B, Mattox S, et al. Superiority of tandem autologous transplantation over standard therapy for previously untreated multiple myeloma. Blood. 1997;89:789–93.

    Article  CAS  Google Scholar 

  11. Cavo M, Pantani L, Petrucci MT, Patriarca F, Zamagni E, Donnarumma D, et al. Bortezomib-thalidomide-dexamethasone is superior to thalidomide-dexamethasone as consolidation therapy after autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma. Blood. 2012;120:9–19.

    Article  CAS  Google Scholar 

  12. Attal M, Harousseau JL, Facon T, Guilhot F, Doyen C, Fuzibet JG, et al. Single versus double autologous stem-cell transplantation for multiple myeloma. N. Engl J Med. 2003;349:2495–502.

    Article  CAS  Google Scholar 

  13. Cavo M, Gay FM, Patriarca F, Zamagni E, Montefusco V, Dozza L, et al. Double autologous stem cell transplantation significantly prolongs progression-free survival and overall survival in comparison with single autotransplantation in newly diagnosed multiple myeloma: an analysis of phase 3 EMN02/HO95 study. Blood. 2017;130(suppl 1):401.

    Google Scholar 

  14. Stadtmauer EA, Pasquini MC, Blackwell B, Hari P, Bashey A, Devine S, et al. Autologous transplantation, consolidation, and maintenance therapy in multiple myeloma: results of the BMT CTN 0702 trial. J Clin Oncol. 2019;37:589–97.

    Article  CAS  Google Scholar 

  15. Boyd KD, Ross FM, Chiecchio L, Dagrada GP, Konn ZJ, Tapper WJ, et al. A novel prognostic model in myeloma based on co-segregating adverse FISH lesions and the ISS: analysis of patients treated in the MRC Myeloma IX trial. Leukemia. 2012;26:349–55.

    Article  CAS  Google Scholar 

  16. Hebraud B, Magrangeas F, Cleynen A, Lauwers-Cances V, Chretien ML, Hulin C, et al. Role of additional chromosomal changes in the prognostic value of t(4;14) and del(17p) in multiple myeloma: the IFM experience. Blood. 2015;125:2095–100.

    Article  CAS  Google Scholar 

  17. Perrot A, Lauwers-Cances V, Tournay E, Hulin C, Chretien ML, Royer B, et al. Development and validation of a cytogenetic prognostic index predicting survival in multiple myeloma. J Clin Oncol. 2019;37:1657–65.

    Article  CAS  Google Scholar 

  18. Attal M, Lauwers-Cances V, Hulin C, Leleu X, Caillot D, Escoffre M, et al. Lenalidomide, bortezomib, and dexamethasone with transplantation for myeloma. N. Engl J Med. 2017;376:1311–20.

    Article  CAS  Google Scholar 

  19. Saini N, Ma J, Milton DR, Patel R, Varma A, Bashir Q, et al. Impact of autologous transplantation in patients with multiple myeloma with t(11;14): a propensity-score matched analysis. Clin Cancer Res. 2019;25:6781–7.

    Article  Google Scholar 

  20. Ziogas DC, Dimopoulos MA, Kastritis E. Prognostic factors for multiple myeloma in the era of novel therapies. Expert Rev Hematol. 2018;11:863–79.

    Article  CAS  Google Scholar 

  21. Kumar SK, Rajkumar SV. The multiple myelomas - current concepts in cytogenetic classification and therapy. Nat Rev Clin Oncol. 2018;15:409–21.

    Article  CAS  Google Scholar 

  22. Dhakal B, Szabo A, Chhabra S, Hamadani M, D’Souza A, Usmani SZ, et al. Autologous transplantation for newly diagnosed multiple myeloma in the era of novel agent induction: a systematic review and meta-analysis. JAMA Oncol. 2018;4:343–50.

    Article  Google Scholar 

  23. Cavo M, Goldschmidt H, Rosinol L, Pantani L, Zweegman S, Salwender HJ, et al. Double vs single autologous stem cell transplantation for newly diagnosed multiple myeloma: long-term follow-up (10-years) analysis of randomized phase 3 studies. Blood. 2018;132(suppl 1):124.

    Article  Google Scholar 

  24. Gagelmann N, Eikema DJ, Koster L, Caillot D, Pioltelli P, Lleonart JB, et al. Tandem Autologous stem cell transplantation improves outcomes in newly diagnosed multiple myeloma with extramedullary disease and high-risk cytogenetics: a study from the chronic malignancies working party of the European Society for Blood and Marrow Transplantation. Biol Blood Marrow Transpl. 2019;25:2134–42.

    Article  CAS  Google Scholar 

  25. Cavo M, Salwender H, Rosinol L, Moreau P, Petrucci MT, Blau IW, et al. Double vs single autologous stem cell transplantation after bortezomib-based induction regimens for multiple myeloma: an integrated analysis of patient-level data from phase European III studies. Blood. 2013;122:767.

    Article  Google Scholar 

  26. Voorhees PM, Kaufman JL, Laubach JP, Sborov DW, Reeves B, Rodriguez C, et al. Daratumumab, lenalidomide, bortezomib, & dexamethasone for transplant-eligible newly diagnosed multiple myeloma: GRIFFIN. Blood. 2020; https://doi.org/10.1182/blood.2020005288.

  27. Gay F, Engelhardt M, Terpos E, Wäsch R, Giaccone L, Auner HW, et al. From transplant to novel cellular therapies in multiple myeloma: European Myeloma Network guidelines and future perspectives. Haematologica. 2018;103:197–211.

    Article  CAS  Google Scholar 

  28. Bruno B, Rotta M, Patriarca F, Mordini N, Allione B, Carnevale-Schianca F, et al. A comparison of allografting with autografting for newly diagnosed myeloma. N. Engl J Med. 2007;356:1110–20.

    Article  CAS  Google Scholar 

  29. Kröger N, Badbaran A, Zabelina T, Ayuk F, Wolschke C, Alchalby H, et al. Impact of high-risk cytogenetics and achievement of molecular remission on long-term freedom from disease after autologous-allogeneic tandem transplantation in patients with multiple myeloma. Biol Blood Marrow Transpl. 2013;19:398–404.

    Article  Google Scholar 

  30. Knop S, Engelhardt M, Liebisch P, Meisner C, Holler E, Metzner B, et al. Allogeneic transplantation in multiple myeloma: long-term follow-up and cytogenetic subgroup analysis. Leukemia. 2019;33:2710–9.

    Article  CAS  Google Scholar 

  31. Schönland SO, Iacobelli S, Koster L, Blaise D, Potter M, Cornelissen JJ, et al. Comparison of different upfront transplant strategies in multiple myeloma - a large registry study from Chronic Malignancies Working Party of EBMT. Blood. 2019;134(Supplement_1):324.

    Article  Google Scholar 

  32. Costa L, Iacobelli S, Pasquini M, Modi R, Giaccone L, Blade J, et al. Long-term survival of 1338 MM patients treated with tandem autologous vs. autologous-allogeneic transplantation. Bone Marrow Transplant. 2020; https://doi.org/10.1038/s41409-020-0887-4.

  33. McCarthy PL, Holstein SA, Petrucci MT, Richardson PG, Hulin C, Tosi P, et al. Lenalidomide maintenance after autologous stem-cell transplantation in newly diagnosed multiple myeloma: a meta-analysis. J Clin Oncol. 2017;35:3279–89.

    Article  CAS  Google Scholar 

  34. Goldschmidt H, Lokhorst HM, Mai EK, van der Holt B, Blau IW, Zweegman S, et al. Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMG-HD4 trial. Leukemia. 2018;32:383–90.

    Article  CAS  Google Scholar 

  35. Gay F, Jackson G, Rosiñol L, Holstein SA, Moreau P, Spada S, et al. Maintenance treatment and survival in patients with myeloma: a systematic review and network meta-analysis. JAMA Oncol. 2018;4:1389–97.

    Article  Google Scholar 

  36. Dimopoulos MA, Gay F, Schjesvold F, Beksac M, Hajek R, Weisel KC, et al. Oral ixazomib maintenance following autologous stem cell transplantation (TOURMALINE-MM3): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet. 2019;393:253–64.

    Article  CAS  Google Scholar 

  37. Gran C, Wang J, Nahi H, Koster L, Gahrton G, Einsele H, et al. Treosulfan conditioning for allogeneic transplantation in multiple myeloma - improved overall survival in first line haematopoietic stem cell transplantation - a large retrospective study by the Chronic Malignancies Working Party of the EBMT. Br J Haematol. 2020; https://doi.org/10.1111/bjh.16642.

  38. Walker BA, Mavrommatis K, Wardell CP, Ashby TC, Bauer M, Davies F, et al. A high-risk, double-hit, group of newly diagnosed myeloma identified by genomic analysis. Leukemia. 2019;33:159–70.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Nico Gagelmann & Nicolaus Kröger

  2. EBMT Statistical Unit and Data Office Leiden, Leiden, The Netherlands

    Diderik-Jan Eikema, Simona Iacobelli & Linda Koster

  3. Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands

    Liesbeth C. de Wreede

  4. Department of Oncology-Hematology, University of Milan and Azienda Socio Sanitaria Territoriale, Papa Giovanni XXIII, Bergamo, Italy

    Alessandro Rambaldi

  5. Hôpital d’Enfants Dijon, Dijon, France

    Denis Caillot

  6. Institut Paoli-Calmettes, Marseille, France

    Didier Blaise

  7. Dél-pesti Centrumkórház-Országos Hematológiai és Infektológiai Intézet, Budapest, Hungary

    Péter Remémyi

  8. CHU Grenoble Alpes - Université Grenoble Alpes, Grenoble, France

    Claude-Eric Bulabois

  9. University Hospital Basel, Basel, Switzerland

    Jakob Passweg

  10. Hopital La Miletrie, Poitiers, France

    Xavier Leleu

  11. University Med. Center Ljubljana, Ljubljana, Slovenia

    Samo Zver

  12. Department of Hematology, University Hospital, Heinrich Heine University, Düsseldorf, Germany

    Guido Kobbe

  13. Karolinska University Hospital, Stockholm, Sweden

    Per Ljungman

  14. CHU Nantes, Nantes, France

    Patrice Chevallier

  15. Klinikum Karlsruhe gGmbH, Karlsruhe, Germany

    Mark Ringhoffer

  16. Leicester Royal Infirmary, Leicester, UK

    Murray Martin

  17. Turku University Hospital, Turku, Finland

    Urpu Salmenniemi

  18. Cliniques Universitaires St. Luc, Brussels, Belgium

    Xavier Poiré

  19. Skanes University Hospital, Lund, Sweden

    Stig Lenhoff

  20. Ospedale San Gerardo, Monza, Italy

    Pietro Pioltelli

  21. Az. Ospedaliera S. Croce e Carle, Cuneo, Italy

    Nicola Mordini

  22. University Hospital Gasthuisberg, Leuven, Belgium

    Michel Delforge

  23. Hôpital Saint Antoine, Paris, France

    Laurent Garderet

  24. University of Heidelberg, Heidelberg, Germany

    Stefan Schönland

  25. CHU de Lille, LIRIC, INSERM U995, Université de Lille, 59000, Lille, France

    Ibrahim Yakoub-Agha

Authors
  1. Nico Gagelmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Diderik-Jan Eikema
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Liesbeth C. de Wreede
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alessandro Rambaldi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Simona Iacobelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Linda Koster
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Denis Caillot
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Didier Blaise
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Péter Remémyi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Claude-Eric Bulabois
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Jakob Passweg
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Xavier Leleu
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Samo Zver
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Guido Kobbe
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Per Ljungman
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Patrice Chevallier
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Mark Ringhoffer
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Murray Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Urpu Salmenniemi
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Xavier Poiré
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Stig Lenhoff
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Pietro Pioltelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Nicola Mordini
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Michel Delforge
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. Laurent Garderet
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. Stefan Schönland
    View author publications

    You can also search for this author in PubMed Google Scholar

  27. Ibrahim Yakoub-Agha
    View author publications

    You can also search for this author in PubMed Google Scholar

  28. Nicolaus Kröger
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

NG and NK designed the study, analyzed data, interpreted results, and wrote the first draft of the manuscript; DJE, LCdW, and SI analyzed data and interpreted results; all authors contributed to writing the manuscript and approved the final version.

Corresponding author

Correspondence to Nicolaus Kröger.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gagelmann, N., Eikema, DJ., de Wreede, L.C. et al. Upfront stem cell transplantation for newly diagnosed multiple myeloma with del(17p) and t(4;14): a study from the CMWP-EBMT. Bone Marrow Transplant 56, 210–217 (2021). https://doi.org/10.1038/s41409-020-01007-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41409-020-01007-w

This article is cited by

Search

Advanced search

Quick links