Skip to main content
SpringerLink
Log in

The impact of re-induction prior to salvage autologous stem cell transplantation in multiple myeloma

  • Article
  • Published:
Bone Marrow Transplantation Submit manuscript

Abstract

Autologous stem cell transplantation (ASCT) is an integral component of the therapeutic arsenal in multiple myeloma. Given that overall survival (OS) is comparable between patients receiving up-front or delayed ASCT, some opt to collect stem cells and postpone transplant until the time of disease progression (i.e., salvage ASCT). It is unknown if induction should be repeated prior to salvage ASCT, or if patients should proceed directly. We identified 234 patients who underwent salvage ASCT at our institution: 188 (80%) were re-induced, whereas 46 (20%) proceeded directly without re-induction. There was no significant difference in time to next therapy (TNT) or OS from Day 0 between the two groups. Patients who were re-induced had a nonsignificant trend towards a higher rate of complete response post-ASCT (45 vs. 33%, p = .12). In multivariate models, re-induction did not affect TNT/OS. In the subgroup of 188 patients who were re-induced, patients with relapsed/refractory disease at the time of ASCT had significantly shorter TNT/OS compared to patients with deeper pre-ASCT responses. In summary, there was no survival difference for patients who were re-induced before salvage ASCT. However, many factors affect the decision to re-induce, and prospective studies would be required to discern its role definitively.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Kumar SK, Rajkumar V, Kyle RA, van Duin M, Sonneveld P, Mateos MV, et al. Multiple myeloma. Nat Rev Dis Prim. 2017;3:17046.

    Article  Google Scholar 

  2. Ravi P, Kumar SK, Cerhan JR, Maurer MJ, Dingli D, Ansell SM, et al. Defining cure in multiple myeloma: a comparative study of outcomes of young individuals with myeloma and curable hematologic malignancies. Blood Cancer J. 2018;8:26.

    Article  Google Scholar 

  3. Kumar SK, Dispenzieri A, Lacy MQ, Gertz MA, Buadi FK, Pandey S, et al. Continued improvement in survival in multiple myeloma: changes in early mortality and outcomes in older patients. Leukemia. 2014;28:1122–8.

    Article  CAS  Google Scholar 

  4. Sidiqi MH, Aljama MA, Bin Riaz I, Dispenzieri A, Muchtar E, Buadi FK, et al. Bortezomib, lenalidomide, and dexamethasone (VRd) followed by autologous stem cell transplant for multiple myeloma. Blood Cancer J. 2018;8:106.

    Article  Google Scholar 

  5. 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 Francais du Myelome. N Engl J Med. 1996;335:91–7.

    Article  CAS  Google Scholar 

  6. Child JA, Morgan GJ, Davies FE, Owen RG, Bell SE, Hawkins K, et al. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med. 2003;348:1875–83.

    Article  CAS  Google Scholar 

  7. Mahajan S, Tandon N, Kumar S. The evolution of stem-cell transplantation in multiple myeloma. Ther Adv Hematol. 2018;9:123–33.

    Article  Google Scholar 

  8. 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 

  9. Gonsalves WI, Buadi FK, Ailawadhi S, Bergsagel PL, Chanan Khan AA, Dingli, D et al. Utilization of hematopoietic stem cell transplantation for the treatment of multiple myeloma: a Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus statement. Bone Marrow Transpl. 2018; https://doi.org/10.1038/s41409-018-0264-8.

    Article  Google Scholar 

  10. D’Souza A, Lee S, Zhu X, Pasquini M. Current use and trends in hematopoietic cell transplantation in the United States. Biol Blood Marrow Transpl. 2017;23:1417–21.

    Article  Google Scholar 

  11. Shah N, Callander N, Ganguly S, Gul Z, Hamadani M, Costa L, et al. Hematopoietic stem cell transplantation for multiple myeloma: guidelines from the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2015;21:1155–66.

    Article  Google Scholar 

  12. Kumar SK, Buadi FK, Rajkumar SV. Pros and cons of frontline autologous transplant in multiple myeloma: the debate over timing. Blood. 2019;133:652–9.

    Article  CAS  Google Scholar 

  13. Dunavin NC, Wei L, Elder P, Phillips GS, Benson DM Jr, Hofmeister CC, et al. Early versus delayed autologous stem cell transplant in patients receiving novel therapies for multiple myeloma. Leuk Lymphoma. 2013;54:1658–64.

    Article  CAS  Google Scholar 

  14. Kumar SK, Lacy MQ, Dispenzieri A, Buadi FK, Hayman SR, Dingli D, et al. Early versus delayed autologous transplantation after immunomodulatory agents-based induction therapy in patients with newly diagnosed multiple myeloma. Cancer. 2012;118:1585–92.

    Article  Google Scholar 

  15. Richardson PG, Laubach JP, Munshi NC, Anderson KC. Early or delayed transplantation for multiple myeloma in the era of novel therapy: does one size fit all? Hematol Am Soc Hematol Educ Program. 2014;2014:255–61.

    Article  Google Scholar 

  16. Sidana S, Tandon N, Dispenzieri A, Gertz MA, Buadi FK, Lacy MQ, et al. Relapse after complete response in newly diagnosed multiple myeloma: implications of duration of response and patterns of relapse. Leukemia. 2019;33:730–8.

    Article  CAS  Google Scholar 

  17. Lahuerta JJ, Paiva B, Vidriales MB, Cordón L, Cedena MT, Puig N, et al. Depth of response in multiple myeloma: a pooled analysis of three PETHEMA/GEM clinical trials. J Clin Oncol. 2017;35:2900–10.

    Article  CAS  Google Scholar 

  18. Kapoor P, Kumar SK, Dispenzieri A, Lacy MQ, Buadi F, Dingli D, et al. Importance of achieving stringent complete response after autologous stem-cell transplantation in multiple myeloma. J Clin Oncol. 2013;31:4529–35.

    Article  Google Scholar 

  19. Vij R, Kumar S, Zhang MJ, Zhong X, Huang J, Dispenzieri A, et al. Impact of pretransplant therapy and depth of disease response before autologous transplantation for multiple myeloma. Biol Blood Marrow Transplant. 2015;21:335–41.

    Article  Google Scholar 

  20. Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15:e538–48.

    Article  Google Scholar 

  21. International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol. 2003;121:749–57.

    Article  Google Scholar 

  22. Durie BG, Harousseau JL, Miguel JS, Bladé J, Barlogie B, Anderson K, et al. International uniform response criteria for multiple myeloma. Leukemia. 2006;20:1467–73.

    Article  CAS  Google Scholar 

  23. Kumar S, Paiva B, Anderson KC, Durie B, Landgren O, Moreau P, et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol. 2016;17:e328–46.

    Article  Google Scholar 

  24. Greipp PR, San Miguel J, Durie BG, Crowley JJ, Barlogie B, Blade J, et al. International staging system for multiple myeloma. J Clin Oncol. 2005;23:3412–20.

    Article  Google Scholar 

  25. Dispenzieri A, Kyle R, Merlini G, Miguel J, Ludwig H, Hajek R, et al. International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders. Leukemia. 2009;23:215–24.

    Article  CAS  Google Scholar 

  26. Rajkumar SV, Harousseau JL, Durie B, Anderson KC, Dimopoulos M, Kyle R, et al. Consensus recommendations for the uniform reporting of clinical trials: report of the International Myeloma Workshop Consensus Panel 1. Blood. 2011;117:4691–5.

    Article  CAS  Google Scholar 

  27. Rajkumar SV, Richardson P, San Miguel JF. Guidelines for determination of the number of prior lines of therapy in multiple myeloma. Blood. 2015;126:921–2.

    Article  CAS  Google Scholar 

  28. Schemper M, Smith TL. A note on quantifying follow-up in studies of failure time. Control Clin Trials. 1996;17:343–6.

    Article  CAS  Google Scholar 

  29. Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transpl. 2013;48:452–8.

    Article  CAS  Google Scholar 

  30. van Rhee F, Giralt S, Barlogie B. The future of autologous stem cell transplantation in myeloma. Blood. 2014;124:328–33.

    Article  Google Scholar 

  31. Shah GL, Winn AN, Lin P-J, Klein A, Sprague KA, Smith HP, et al. Cost-effectiveness of autologous hematopoietic stem cell transplantation for elderly patients with multiple myeloma using the surveillance, epidemiology, and end results-medicare database. Biol Blood Marrow Transplant. 2015;21:1823–9.

    Article  Google Scholar 

  32. Paiva B, Vídriales MB, Rosiñol L, Martínez-López J, Mateos MV, Ocio EM, et al. A multiparameter flow cytometry immunophenotypic algorithm for the identification of newly diagnosed symptomatic myeloma with an MGUS-like signature and long-term disease control. Leukemia. 2013;27:2056–61.

    Article  CAS  Google Scholar 

  33. Kansagra A, Gonsalves WI, Gertz MA, Buadi FK, Dingli D, Dispenzieri A, et al. Analysis of clinical factors and outcomes associated with nonuse of collected peripheral blood stem cells for autologous stem cell transplants in transplant-eligible patients with multiple myeloma. Biol Blood Marrow Transplant. 2018;24:2127–32.

    Article  Google Scholar 

  34. Rawstron AC, Child JA, de Tute RM, Davies FE, Gregory WM, Bell SE, et al. Minimal residual disease assessed by multiparameter flow cytometry in multiple myeloma: impact on outcome in the Medical Research Council Myeloma IX Study. J Clin Oncol. 2013;31:2540–7.

    Article  Google Scholar 

  35. Sellner L, Heiss C, Benner A, Raab MS, Hillengass J, Hose D, et al. Autologous retransplantation for patients with recurrent multiple myeloma: a single-center experience with 200 patients. Cancer. 2013;119:2438–46.

    Article  CAS  Google Scholar 

  36. Gonsalves WI, Gertz MA, Lacy MQ, Dispenzieri A, Hayman SR, Buadi FK, et al. Second auto-SCT for treatment of relapsed multiple myeloma. Bone Marrow Transplant. 2013;48:568–73.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We would like to acknowledge the patients and their families. KM was supported by CTSA Grant Number TL1TR002380 from the National Center for Advancing Translational Sciences (NCATS).

Author information

Authors and Affiliations

  1. Mayo Clinic School of Medicine, Rochester, MN, USA

    Kevin C. Miller

  2. Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA

    Morie A. Gertz, Francis K. Buadi, Suzanne R. Hayman, Martha Q. Lacy, Angela A. Dispenzieri, David Dingli, Prashant Kapoor, Wilson I. Gonsalves, Taxiarchis Kourelis, Eli Muchtar, William J. Hogan & Shaji K. Kumar

Authors
  1. Kevin C. Miller
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Morie A. Gertz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Francis K. Buadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Suzanne R. Hayman
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Martha Q. Lacy
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Angela A. Dispenzieri
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. David Dingli
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Prashant Kapoor
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Wilson I. Gonsalves
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Taxiarchis Kourelis
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Eli Muchtar
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. William J. Hogan
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Shaji K. Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shaji K. Kumar.

Ethics declarations

Conflict of interest

SK has obtained research support for clinical trials from Celgene, Millennium, Novartis, Janssen, and Sanofi. AD has received research support for clinical trials from Pfizer, Jannsen, Millennium, Alnylam, and Celgene. MAG has received research support from ISIS and Prothena, and honoraria from Celgene, Millennium Pharmaceuticals, and Novartis. The remaining 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.

Parts of these data were presented on Poster 4613 at the American Society of Hematology Annual Meeting in San Diego, California on 03 December 2018.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Miller, K.C., Gertz, M.A., Buadi, F.K. et al. The impact of re-induction prior to salvage autologous stem cell transplantation in multiple myeloma. Bone Marrow Transplant 54, 2039–2050 (2019). https://doi.org/10.1038/s41409-019-0590-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41409-019-0590-5

  • Springer Nature Limited

This article is cited by

Search

Navigation