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Autologous stem cell transplantation in elderly patients with multiple myeloma in Korea: the KMM1807 study

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Abstract

Autologous stem cell transplantation (ASCT) is not frequently performed for elderly patients multiple myeloma (MM) in Korea, despite its being a standardized approach for young patients. Medical records of 150 patients from 15 Korean institutions who received ASCT at age ≥ 64 years were analyzed retrospectively. Patients included had symptomatic MM, and had received their first ASCT at age ≥ 64 following induction chemotherapy. The main outcome was the response after ASCT. Overall survival (OS) and progression-free survival (PFS) were also analyzed. Median time to ASCT was 6.3 months. Complete response plus stringent complete response rate increased from 36 (24.0%) to 105 (70.0%) after ASCT, and high-quality response (≥ very good partial response) increased from 96 (64.0%) to 125 (83.3%). With a median follow-up of 32.6 months after ASCT, 5-year OS and PFS were 59.7% and 22.8%, respectively. Febrile neutropenia occurred in 43.5%, and nausea (21.3%) and stomatitis (13.2%) were common grade 3–4 non-hematologic adverse events. Of 44 deaths, disease progression (n = 23) was the most common cause of mortality, followed by infection (n = 13). Treatment-related death occurred in four cases (2.7%). ASCT is an effective and safe option for elderly MM patients and is associated with superior clinical outcomes.

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References

  1. Kyle RA, Gertz MA, Witzig TE, Lust JA, Lacy MQ, Dispenzieri A, et al. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc. 2003;78(1):21–33.

    Article  PubMed  Google Scholar 

  2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7–34.

    Article  PubMed  Google Scholar 

  3. Lee JH, Lee DS, Lee JJ, Chang YH, Jin JY, Jo DY, et al. Multiple myeloma in Korea: past, present, and future perspectives. Experience of the Korean Multiple Myeloma Working Party. Int J Hematol. 2010;92(1):52–7.

    Article  PubMed  Google Scholar 

  4. Liu W, Liu J, Song Y, Wang X, Zhou M, Wang L, et al. Mortality of lymphoma and myeloma in China, 2004–2017: an observational study. J Hematol Oncol. 2019;12(1):22.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Chen JH, Chung CH, Wang YC, Hsu SN, Huang WY, Chien WC. Prevalence and mortality-related factors of multiple myeloma in Taiwan. PLoS ONE. 2016;11(12):e0167227.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Hyun KR, Kang S, Lee S. Population aging and healthcare expenditure in Korea. Health Econ. 2016;25(10):1239–51.

    Article  PubMed  Google Scholar 

  7. Hong J, Lee JH. Recent advances in multiple myeloma: a Korean perspective. Korean J Intern Med. 2016;31(5):820–34.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Ntanasis-Stathopoulos I, Gavriatopoulou M, Kastritis E, Terpos E, Dimopoulos MA. Multiple myeloma: Role of autologous transplantation. Cancer Treat Rev. 2020;82:101929.

    Article  CAS  PubMed  Google Scholar 

  9. 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):52–61.

    Article  Google Scholar 

  10. Gertz MA, Dingli D. How we manage autologous stem cell transplantation for patients with multiple myeloma. Blood. 2014;124(6):882–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. 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(6):587–600.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Mizuno S, Kawamura K, Hanamura I, Sunami K, Mori T, Nakamura F, et al. Efficacy and safety of autologous stem cell transplantation in patients aged ≥ 65 years with multiple myeloma in the era of novel agents. Bone Marrow Transplant. 2019;54(10):1595–604. https://doi.org/10.1038/s41409-019-0478-4.

    Article  CAS  PubMed  Google Scholar 

  13. Stettler J, Novak U, Baerlocher GM, Seipel K, Mansouri Taleghani B, Pabst T. Autologous stem cell transplantation in elderly patients with multiple myeloma: evaluation of its safety and efficacy. Leuk Lymphoma. 2017;58(5):1076–83.

    Article  PubMed  Google Scholar 

  14. Bashir Q, Shah N, Parmar S, Wei W, Rondon G, Weber DM, et al. Feasibility of autologous hematopoietic stem cell transplant in patients aged ≥ 70 years with multiple myeloma. Leuk Lymphoma. 2012;53(1):118–22.

    Article  CAS  PubMed  Google Scholar 

  15. Kumar SK, Dingli D, Lacy MQ, Dispenzieri A, Hayman SR, Buadi FK, et al. Autologous stem cell transplantation in patients of 70 years and older with multiple myeloma: results from a matched pair analysis. Am J Hematol. 2008;83(8):614–7.

    Article  PubMed  Google Scholar 

  16. Jantunen E, Kuittinen T, Penttila K, Lehtonen P, Mahlamaki E, Nousiainen T. High-dose melphalan (200 mg/m2) supported by autologous stem cell transplantation is safe and effective in elderly (≥65 years) myeloma patients: comparison with younger patients treated on the same protocol. Bone Marrow Transplant. 2006;37(10):917–22.

    Article  CAS  PubMed  Google Scholar 

  17. Reece DE, Bredeson C, Perez WS, Jagannath S, Zhang MJ, Ballen KK, et al. Autologous stem cell transplantation in multiple myeloma patients <60 vs ≥60 years of age. Bone Marrow Transplant. 2003;32(12):1135–43.

    Article  CAS  PubMed  Google Scholar 

  18. Sirohi B, Powles R, Treleaven J, Mainwaring P, Kulkarni S, Pandha H, et al. The role of autologous transplantation in patients with multiple myeloma aged 65 years and over. Bone Marrow Transplant. 2000;25(5):533–9.

    Article  CAS  PubMed  Google Scholar 

  19. Ozaki S, Harada T, Saitoh T, Shimazaki C, Itagaki M, Asaoku H, et al. Survival of multiple myeloma patients aged 65–70 years in the era of novel agents and autologous stem cell transplantation. A multicenter retrospective collaborative study of the Japanese Society of Myeloma and the European Myeloma Network. Acta Haematol. 2014;132(2):211–9.

    Article  PubMed  Google Scholar 

  20. Facon T, Mary JY, Hulin C, Benboubker L, Attal M, Pegourie B, et al. Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99–06): a randomised trial. Lancet. 2007;370(9594):1209–18.

    Article  CAS  PubMed  Google Scholar 

  21. Muta T, Miyamoto T, Fujisaki T, Ohno Y, Kamimura T, Kato K, et al. Evaluation of the feasibility and efficacy of autologous stem cell transplantation in elderly patients with multiple myeloma. Intern Med. 2013;52(1):63–70.

    Article  CAS  PubMed  Google Scholar 

  22. Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos M-V, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15(12):e538–e548548.

    Article  PubMed  Google Scholar 

  23. 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(15):3412–20.

    Article  PubMed  Google Scholar 

  24. Palumbo A, Avet-Loiseau H, Oliva S, Lokhorst HM, Goldschmidt H, Rosinol L, et al. Revised international staging system for multiple myeloma: a report from international myeloma working group. J Clin Oncol. 2015;33(26):2863–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Kumar SK, Callander NS, Alsina M, Atanackovic D, Biermann JS, Chandler JC, et al. Multiple Myeloma, Version 3.2017, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2017;15(2):230–69.

    Article  PubMed  Google Scholar 

  26. Merz M, Neben K, Raab MS, Sauer S, Egerer G, Hundemer M, et al. Autologous stem cell transplantation for elderly patients with newly diagnosed multiple myeloma in the era of novel agents. Ann Oncol. 2014;25(1):189–95.

    Article  CAS  PubMed  Google Scholar 

  27. 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(5):1122–8.

    Article  CAS  PubMed  Google Scholar 

  28. Pulte D, Gondos A, Brenner H. Improvement in survival of older adults with multiple myeloma: results of an updated period analysis of SEER data. Oncologist. 2011;16(11):1600–3.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Larocca A, Palumbo A. Optimizing treatment for elderly patients with newly diagnosed multiple myeloma: a personalized approach. J Clin Oncol. 2016;34(30):3600–4.

    Article  PubMed  Google Scholar 

  30. Engelhardt M, Dold SM, Ihorst G, Zober A, Moller M, Reinhardt H, et al. Geriatric assessment in multiple myeloma patients: validation of the International Myeloma Working Group (IMWG) score and comparison with other common comorbidity scores. Haematologica. 2016;101(9):1110–9.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Sharma M, Zhang MJ, Zhong X, Abidi MH, Akpek G, Bacher U, et al. Older patients with myeloma derive similar benefit from autologous transplantation. Biol Blood Marrow Transplant. 2014;20(11):1796–803.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Kim JS, Kim K, Cheong JW, Min YH, Suh C, Kim H, et al. Complete remission status before autologous stem cell transplantation is an important prognostic factor in patients with multiple myeloma undergoing upfront single autologous transplantation. Biol Blood Marrow Transplant. 2009;15(4):463–70.

    Article  CAS  PubMed  Google Scholar 

  33. Lee YJ, Moon JH, Sohn SK, Kim SJ, Jung SH, Lee JJ, et al. Benefits of additional cycles of bortezomib/thalidomide/dexamethasone (VTD) induction therapy compared to four cycles of VTD for newly diagnosed multiple myeloma. Bone Marrow Transplant. 2019;54(12):2051–9.

    Article  CAS  PubMed  Google Scholar 

  34. Sunami K, Matsumoto M, Fuchida SI, Omoto E, Takamatsu H, Adachi Y, et al. Bortezomib-based strategy with autologous stem cell transplantation for newly diagnosed multiple myeloma: a phase II study by the Japan Study Group for Cell Therapy and Transplantation (JSCT-MM12). Int J Clin Oncol. 2019;24(8):966–75.

    Article  CAS  PubMed  Google Scholar 

  35. Auner HW, Szydlo R, Hoek J, Goldschmidt H, Stoppa AM, Morgan GJ, et al. Trends in autologous hematopoietic cell transplantation for multiple myeloma in Europe: increased use and improved outcomes in elderly patients in recent years. Bone Marrow Transplant. 2015;50(2):209–15.

    Article  CAS  PubMed  Google Scholar 

  36. Palumbo A, Bringhen S, Bruno B, Falcone AP, Liberati AM, Grasso M, et al. Melphalan 200 mg/m(2) versus melphalan 100 mg/m(2) in newly diagnosed myeloma patients: a prospective, multicenter phase 3 study. Blood. 2010;115(10):1873–9.

    Article  CAS  PubMed  Google Scholar 

  37. Badros A, Barlogie B, Siegel E, Morris C, Desikan R, Zangari M, et al. Autologous stem cell transplantation in elderly multiple myeloma patients over the age of 70 years. Br J Haematol. 2001;114(3):600–7.

    Article  CAS  PubMed  Google Scholar 

  38. Auner HW, Garderet L, Kroger N. Autologous haematopoietic cell transplantation in elderly patients with multiple myeloma. Br J Haematol. 2015;171(4):453–62.

    Article  PubMed  Google Scholar 

  39. Bashir Q, Thall PF, Milton DR, Fox PS, Kawedia JD, Kebriaei P, et al. Conditioning with busulfan plus melphalan versus melphalan alone before autologous haemopoietic cell transplantation for multiple myeloma: an open-label, randomised, phase 3 trial. Lancet Haematol. 2019;6(5):e266–e275275.

    Article  PubMed  Google Scholar 

  40. Byun JM, Lee J, Shin SJ, Kang M, Yoon SS, Koh Y. Busulfan plus melphalan versus high-dose melphalan as conditioning regimens in autologous stem cell transplantation for newly diagnosed multiple myeloma. Blood Res. 2018;53(2):105–9.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Jung SH, Lee JJ, Kim JS, Min CK, Kim K, Choi Y, et al. Phase 2 study of an intravenous busulfan and melphalan conditioning regimen for autologous stem cell transplantation in patients with multiple myeloma (KMM150). Biol Blood Marrow Transplant. 2018;24(5):923–9.

    Article  CAS  PubMed  Google Scholar 

  42. Reece D, Song K, LeBlanc R, Mezzi K, Olujohungbe A, White D, et al. Efficacy and safety of busulfan-based conditioning regimens for multiple myeloma. Oncologist. 2013;18(5):611–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Palumbo A, Cavallo F, Gay F, Di Raimondo F, Ben Yehuda D, Petrucci MT, et al. Autologous transplantation and maintenance therapy in multiple myeloma. N Engl J Med. 2014;371(10):895–905.

    Article  PubMed  CAS  Google Scholar 

  44. 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(29):3279–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Lee HS, Min CK. Optimal maintenance and consolidation therapy for multiple myeloma in actual clinical practice. Korean J Intern Med. 2016;31(5):809–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Ozaki S, Shimizu K. Autologous stem cell transplantation in elderly patients with multiple myeloma: past, present, and future. Biomed Res Int. 2014;2014:394792.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Lee SE, Kim JH, Jeon YW, Yoon JH, Shin SH, Eom KS, et al. Impact of extramedullary plasmacytomas on outcomes according to treatment approach in newly diagnosed symptomatic multiple myeloma. Ann Hematol. 2015;94(3):445–52.

    Article  CAS  PubMed  Google Scholar 

  48. Wu P, Davies FE, Boyd K, Thomas K, Dines S, Saso RM, et al. The impact of extramedullary disease at presentation on the outcome of myeloma. Leuk Lymphoma. 2009;50(2):230–5.

    Article  CAS  PubMed  Google Scholar 

  49. Li J, Shen KN, Huang WR, Li LH, Chen H, Chen WM, et al. Autologous stem cell transplant can overcome poor prognosis in patients with multiple myeloma with extramedullary plasmacytoma. Leuk Lymphoma. 2014;55(7):1687–90.

    Article  PubMed  Google Scholar 

  50. Lonial S, Weiss BM, Usmani SZ, Singhal S, Chari A, Bahlis NJ, et al. Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomised, phase 2 trial. Lancet. 2016;387(10027):1551–600.

    Article  CAS  PubMed  Google Scholar 

  51. Palumbo A, Chanan-Khan A, Weisel K, Nooka AK, Masszi T, Beksac M, et al. Daratumumab, bortezomib, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375(8):754–66.

    Article  CAS  PubMed  Google Scholar 

  52. Dimopoulos MA, Oriol A, Nahi H, San-Miguel J, Bahlis NJ, Usmani SZ, et al. Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375(14):1319–31.

    Article  CAS  PubMed  Google Scholar 

  53. Stewart AK, Rajkumar SV, Dimopoulos MA, Masszi T, Spicka I, Oriol A, et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2015;372(2):142–52.

    Article  PubMed  CAS  Google Scholar 

  54. Dimopoulos MA, Palumbo A, Corradini P, Cavo M, Delforge M, Di Raimondo F, et al. Safety and efficacy of pomalidomide plus low-dose dexamethasone in STRATUS (MM-010): a phase 3b study in refractory multiple myeloma. Blood. 2016;128(4):497–503.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This study was performed with the collaboration of 15 institutions belonging to the Korean Multiple Myeloma Working Party (KMMWP).

Funding

This research was supported by National Cancer Center research Grant (1911262-2).

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Authors and Affiliations

  1. Center for Hematologic Malignancy, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Geyonggi, 410-769, Republic of Korea

    Jongheon Jung & Hyeon-Seok Eom

  2. Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon, Korea

    Yoon Seok Choi

  3. Division of Hematology, Gachon University College of Medicine Gil Medical Center, Incheon, Korea

    Jae Hoon Lee

  4. Department of Internal Medicine, Hemato-Oncology, Inje University Busan Paik Hospital, Busan, Republic of Korea

    Won Sik Lee

  5. Department of Internal Medicine, Dong-A Medical Center, Dong-A University College of Medicine, Busan, Korea

    Sung-hyun Kim

  6. Department of Internal Medicine, Korea University School of Medicine, Seoul, Korea

    Yong Park

  7. Department of Hematology-Oncology, Wonkwang University Hospital, Iksan, Korea

    Seung-Shin Lee

  8. Department of Hemato-Oncology, Dongsan Medical Center, Keimyung University, Daegu, South Korea

    Young Rok Do

  9. Department of Hematology-Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea

    Jae-Cheol Jo

  10. Department of Hematology-Oncology, Chonnam National University Hwasun Hospital/Chonnam National University Medical School, Hwasun, Jeollanamdo, Republic of Korea

    Je-Jung Lee

  11. Division of Hematology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea

    Jin Seok Kim

  12. Division of Hematology-Oncology, Department of Internal Medicine, Medical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Korea

    Ho-Jin Shin

  13. Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea

    Dong-Yeop Shin & Sung-Soo Yoon

  14. Department of Hematology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

    Chang-Ki Min

  15. Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, South Korea

    Kihyun Kim

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  1. Jongheon Jung
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The Korean Multiple Myeloma Working Party (KMMWP)

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Jung, J., Choi, Y.S., Lee, J.H. et al. Autologous stem cell transplantation in elderly patients with multiple myeloma in Korea: the KMM1807 study. Int J Hematol 112, 84–95 (2020). https://doi.org/10.1007/s12185-020-02869-y

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