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Optimal timing of treatment at relapse after autologous stem cell transplantation in patients with multiple myeloma: a study of the Korean Multiple Myeloma Working Party (KMM-1909)


The effectiveness of early treatment for biochemical relapse of multiple myeloma (MM) is unclear. To clarify this issue, this retrospective study was performed to evaluate the survival outcomes of 315 patients with relapsed MM after upfront autologous stem cell transplantation (ASCT). Over a median follow-up of 66.6 months (range, 15.1–195.5 months), 48.2% of patients showed biochemical relapse, 41.3% showed clinical relapse, and 10.5% showed significant biochemical relapse. Progression-free survival (PFS) and overall survival (OS) were inferior for patients with clinical relapse compared to the other patients. Multivariate analysis showed that clinical relapse was an independent prognostic factor for OS. In patients with biochemical relapse, there was no significant difference in survival between patients treated while asymptomatic and those treated once clinical symptoms had appeared. Relapse type after upfront ASCT was a significant prognostic factor in patients with MM. In addition, no survival benefit of early treatment at biochemical relapse was observed, but a triplet regimen may be beneficial for MM patients with biochemical relapse.

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Fig. 1: Survival outcomes by relapse type after autologous stem cell transplantation.
Fig. 2: Outcomes by treatment timing and salvage therapy in patients with biochemical relapse.

Data availability

The dataset is available from the corresponding author upon reasonable request (the fighshare doi-


  1. Kyle RA, Rajkumar SV. Multiple myeloma. N Engl J Med. 2004;351:1860–1873.

    Article  CAS  PubMed  Google Scholar 

  2. Cavo M, Gay F, Beksac M, Pantani L, Petrucci MT, Dimopoulos MA, et al. Autologous haematopoietic stem-cell transplantation versus bortezomib-melphalan-prednisone, with or without bortezomib-lenalidomide-dexamethasone consolidation therapy, and lenalidomide maintenance for newly diagnosed multiple myeloma (EMN02/HO95): a multicentre, randomised, open-label, phase 3 study. Lancet Haematol. 2020;7:e456–e468.

    Article  PubMed  Google Scholar 

  3. Zamarin D, Giralt S, Landau H, Lendvai N, Lesokhin A, Chung D, et al. Patterns of relapse and progression in multiple myeloma patients after auto-SCT: implications for patients’ monitoring after transplantation. Bone Marrow Transpl. 2013;48:419–424.

    Article  CAS  Google Scholar 

  4. Laubach J, Garderet L, Mahindra A, Gahrton G, Caers J, Sezer O, et al. Management of relapsed multiple myeloma: recommendations of the International Myeloma Working Group. Leukemia. 2016;30:1005–1017.

    Article  CAS  PubMed  Google Scholar 

  5. Kumar SK, Rajkumar SV, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood. 2008;111:2516–2520.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. 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;28:1122–1128.

    Article  CAS  PubMed  Google Scholar 

  7. Palumbo A, Rajkumar SV, San Miguel JF, Larocca A, Niesvizky R, Morgan G, et al. International Myeloma Working Group consensus statement for the management, treatment, and supportive care of patients with myeloma not eligible for standard autologous stem-cell transplantation. J Clin Oncol. 2014;32:587–600.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Fernández de Larrea C, Jiménez R, Rosiñol L, Giné E, Tovar N, Cibeira MT, et al. Pattern of relapse and progression after autologous SCT as upfront treatment for multiple myeloma. Bone Marrow Transpl. 2014;49:223–227.

    Article  Google Scholar 

  9. Chim CS, Kumar SK, Orlowski RZ, Cook G, Richardson PG, Gertz MA, et al. Management of relapsed and refractory multiple myeloma: novel agents, antibodies, immunotherapies and beyond. Leukemia. 2018;32:252–262.

    Article  CAS  PubMed  Google Scholar 

  10. Turesson I, Velez R, Kristinsson SY, Landgren O. Patterns of improved survival in patients with multiple myeloma in the twenty-first century: a population-based study. J Clin Oncol. 2010;28:830–834.

    Article  PubMed  Google Scholar 

  11. Pulte D, Jansen L, Castro FA, Emrich K, Katalinic A, Holleczek B, et al. Trends in survival of multiple myeloma patients in Germany and the United States in the first decade of the 21st century. Br J Haematol. 2015;171:189–196.

    Article  PubMed  Google Scholar 

  12. Katodritou E, Kyrtsonis MC, Delimpasi S, Kyriakou D, Symeonidis A, Spanoudakis E, et al. Real-world data on Len/Dex combination at second-line therapy of multiple myeloma: treatment at biochemical relapse is a significant prognostic factor for progression-free survival. Ann Hematol. 2018;97:1671–1682.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Mina R, Belotti A, Petrucci MT, Zambello R, Capra A, Di Lullo G, et al. Bortezomib-dexamethasone as maintenance therapy or early retreatment at biochemical relapse versus observation in relapsed/refractory multiple myeloma patients: a randomized phase II study. Blood Cancer J. 2020;10:58.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Sun Z, Zheng F, Wu S, Liu Y, Guo H, Liu Y. Triplet versus doublet combination regimens for the treatment of relapsed or refractory multiple myeloma: A meta-analysis of phase III randomized controlled trials. Crit Rev Oncol Hematol. 2017;113:249–255.

    Article  PubMed  Google Scholar 

  15. Dimopoulos MA, Moreau P, Terpos E, Mateos MV, Zweegman S, Cook G, et al. Multiple myeloma: EHA-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up(†). Ann Oncol. 2021;32:309–322.

    Article  CAS  PubMed  Google Scholar 

  16. Moreau P, Kumar SK, San Miguel J, Davies F, Zamagni E, Bahlis N, et al. Treatment of relapsed and refractory multiple myeloma: recommendations from the International Myeloma Working Group. Lancet Oncol. 2021;22:e105–e118.

    Article  PubMed  Google Scholar 

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Authors and Affiliations



KK and JJL designed the study; SHJ prepared the manuscript; CKM, JHL, YCM, SMB, DHY, and HSL critically reviewed the manuscript. All authors have read and approved the final manuscript.

Corresponding authors

Correspondence to Kihyun Kim or Je-Jung Lee.

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The authors declare no competing interests.

Ethical approval and consent to participate

This study was approved by the institutional ethics committee of each participating institution and conducted in accordance with the Declaration of Helsinki. The committee waived the need for informed patient consent because of the retrospective nature of the study.

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Jung, SH., Min, CK., Lee, J.H. et al. Optimal timing of treatment at relapse after autologous stem cell transplantation in patients with multiple myeloma: a study of the Korean Multiple Myeloma Working Party (KMM-1909). Bone Marrow Transplant 57, 1797–1802 (2022).

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