Outcomes with autologous stem cell transplant vs. non-transplant therapy in patients 70 years and older with multiple myeloma

Abstract

We evaluated 79 patients with multiple myeloma (MM) ≥70 years referred to our blood and marrow transplant clinic, within 1 year of diagnosis from 2010 to 2019, for consideration of autologous stem cell transplant (ASCT). Thirty-eight (48%) of 79 patients underwent ASCT. ASCT was not pursued in 41 (52%) patients due to: patient or physician preference in 80% (n = 33) or ineligibility in 20% (n = 8). Baseline characteristics of patients in the two groups were similar. Median PFS from treatment start amongst patients undergoing ASCT (n = 38) vs. not (n = 41) was 41 months vs. 33 months, p = 0.03. There was no difference in OS, with estimated 5-year OS of 73% vs. 83%, respectively (p = 0.86). Day +100 transplant-related mortality (TRM) was 0%. ASCT was an independent favorable prognostic factor for PFS in multivariate analysis, after accounting for HCT-CI score, performance status, hematologic response, and maintenance. Finally, patients ≥70 years undergoing ASCT had similar PFS compared to a contemporaneous institutional cohort of patients <70 years (n = 631) (median PFS from transplant: 36 vs. 47 months, p = 0.25). In this retrospective analysis, ASCT was associated with low TRM and better PFS in fit older adults with MM compared to non-transplant therapy, with comparable benefits as seen in younger patients.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: Survival outcomes in patients 70 years and above undergoing ASCT vs. non-ASCT based treatment.
Fig. 2: Progression free survival compared to a younger patient cohort.

References

  1. 1.

    Palumbo A, Bringhen S, Ludwig H, Dimopoulos MA, Blade J, Mateos MV, et al. Personalized therapy in multiple myeloma according to patient age and vulnerability: a report of the European Myeloma Network (EMN). Blood. 2011;118:4519–29. https://doi.org/10.1182/blood-2011-06-358812.

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Smith BD, Smith GL, Hurria A, Hortobagyi GN, Buchholz TA. Future of cancer incidence in the United States: burdens upon an aging, changing nation. J Clin Oncol Off J Am Soc Clin Oncol. 2009;27:2758–65. https://doi.org/10.1200/JCO.2008.20.8983.

    Article  Google Scholar 

  3. 3.

    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;335:91–97. https://doi.org/10.1056/NEJM199607113350204.

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    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. https://doi.org/10.1056/NEJMoa022340.

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    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;132:211–9. https://doi.org/10.1159/000357394.

    Article  PubMed  Google Scholar 

  6. 6.

    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 Off J Eur Soc Med Oncol/ESMO. 2014;25:189–95. https://doi.org/10.1093/annonc/mdt509.

    CAS  Article  Google Scholar 

  7. 7.

    Gay F, Magarotto V, Crippa C, Pescosta N, Guglielmelli T, Cavallo F, et al. Bortezomib induction, reduced-intensity transplantation, and lenalidomide consolidation-maintenance for myeloma: updated results. Blood. 2013;122:1376–83. https://doi.org/10.1182/blood-2013-02-483073.

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    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;53:118–22. https://doi.org/10.3109/10428194.2011.606942.

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    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;83:614–7. https://doi.org/10.1002/ajh.21191.

    Article  PubMed  Google Scholar 

  10. 10.

    Gertz MA, Lacy MQ, Dispenzieri A, Hayman SR, Kumar S, Leung N, et al. Impact of age and serum creatinine value on outcome after autologous blood stem cell transplantation for patients with multiple myeloma. Bone Marrow Transplant. 2007;39:605–11. https://doi.org/10.1038/sj.bmt.1705627.

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    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 (>or=65 years) myeloma patients: comparison with younger patients treated on the same protocol. Bone Marrow Transplant. 2006;37:917–22. https://doi.org/10.1038/sj.bmt.1705360.

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    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;32:1135–43. https://doi.org/10.1038/sj.bmt.1704288.

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    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;52:63–70. https://doi.org/10.2169/internalmedicine.52.8390.

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Wildes TM, Finney JD, Fiala M, Gao F, Vij R, Stockerl-Goldstein K, et al. High-dose therapy and autologous stem cell transplant in older adults with multiple myeloma. Bone Marrow Transplant. 2015;50:1075–82. https://doi.org/10.1038/bmt.2015.106.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. 15.

    Merz M, Jansen L, Castro FA, Hillengass J, Salwender H, Weisel K, et al. Survival of elderly patients with multiple myeloma—effect of upfront autologous stem cell transplantation. Eur J Cancer. 2016;62:1–8. https://doi.org/10.1016/j.ejca.2016.04.004.

    Article  PubMed  Google Scholar 

  16. 16.

    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;25:533–9. https://doi.org/10.1038/sj.bmt.1702188.

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    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;50:209–15. https://doi.org/10.1038/bmt.2014.255.

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Garderet L, Beohou E, Caillot D, Stoppa AM, Touzeau C, Chretien ML, et al. Upfront autologous stem cell transplantation for newly diagnosed elderly multiple myeloma patients: a prospective multicenter study. Haematologica. 2016;101:1390–7. https://doi.org/10.3324/haematol.2016.150334.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Koreth J, Cutler CS, Djulbegovic B, Behl R, Schlossman RL, Munshi NC, et al. High-dose therapy with single autologous transplantation versus chemotherapy for newly diagnosed multiple myeloma: A systematic review and meta-analysis of randomized controlled trials. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant. 2007;13:183–96. https://doi.org/10.1016/j.bbmt.2006.09.010.

    CAS  Article  Google Scholar 

  20. 20.

    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. https://doi.org/10.1056/NEJMoa1611750.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  21. 21.

    International Myeloma Working G. 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. 22.

    Durie BG, Harousseau JL, Miguel JS, Blade J, Barlogie B, Anderson K, et al. International uniform response criteria for multiple myeloma. Leukemia. 2006;20:1467–73. https://doi.org/10.1038/sj.leu.2404284.

    CAS  Article  PubMed  Google Scholar 

  23. 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 Off J Am Soc Clin Oncol. 2005;23:3412–20. https://doi.org/10.1200/JCO.2005.04.242.

    Article  Google Scholar 

  24. 24.

    Saad A, Mahindra A, Zhang MJ, Zhong X, Costa LJ, Dispenzieri A, et al. Hematopoietic cell transplant comorbidity index is predictive of survival after autologous hematopoietic cell transplantation in multiple myeloma. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant. 2014;20:402–8 e401. https://doi.org/10.1016/j.bbmt.2013.12.557.

    Article  Google Scholar 

  25. 25.

    Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG, et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005;106:2912–9. https://doi.org/10.1182/blood-2005-05-2004.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  26. 26.

    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 Off J Am Soc Clin Oncol. 2015;33:2863–9. https://doi.org/10.1200/JCO.2015.61.2267.

    CAS  Article  Google Scholar 

  27. 27.

    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;78:21–33. https://doi.org/10.4065/78.1.21.

    Article  PubMed  Google Scholar 

  28. 28.

    Majhail NS, Brunstein CG, McAvoy S, DeFor TE, Al-Hazzouri A, Setubal D, et al. Does the hematopoietic cell transplantation specific comorbidity index predict transplant outcomes? A validation study in a large cohort of umbilical cord blood and matched related donor transplants. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant. 2008;14:985–92. https://doi.org/10.1016/j.bbmt.2008.06.008.

    CAS  Article  Google Scholar 

  29. 29.

    Berro M, Arbelbide JA, Rivas MM, Basquiera AL, Ferini G, Vitriu A, et al. Hematopoietic cell transplantation-specific comorbidity index predicts morbidity and mortality in autologous stem cell transplantation. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant. 2017;23:1646–50. https://doi.org/10.1016/j.bbmt.2017.06.014.

    Article  Google Scholar 

  30. 30.

    Labonte L, Iqbal T, Zaidi MA, McDiarmid SA, Huebsch LB, Tay J, et al. Utility of comorbidity assessment in predicting transplantation-related toxicity following autologous hematopoietic stem cell transplantation for multiple myeloma. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant. 2008;14:1039–44. https://doi.org/10.1016/j.bbmt.2008.06.019.

    Article  Google Scholar 

  31. 31.

    Jaglowski SM, Ruppert AS, Hofmeister CC, Elder P, Blum W, Klisovic R, et al. The hematopoietic stem cell transplant comorbidity index can predict for 30-day readmission following autologous stem cell transplant for lymphoma and multiple myeloma. Bone Marrow Transplant. 2014;49:1323–9. https://doi.org/10.1038/bmt.2014.155.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  32. 32.

    Palumbo A, Bringhen S, Mateos MV, Larocca A, Facon T, Kumar SK, et al. Geriatric assessment predicts survival and toxicities in elderly myeloma patients: an International Myeloma Working Group report. Blood. 2015;125:2068–74. https://doi.org/10.1182/blood-2014-12-615187.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Durie BGM, Hoering A, Abidi MH, Rajkumar SV, Epstein J, Kahanic SP, et al. Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial. Lancet. 2017;389:519–27. https://doi.org/10.1016/s0140-6736(16)31594-x.

    CAS  Article  PubMed  Google Scholar 

  34. 34.

    Kumar S, Jacobus SJ, Cohen AD, Weiss M, Callander NS, Singh AA, et al. Carfilzomib, lenalidomide, and dexamethasone (KRd) versus bortezomib, lenalidomide, and dexamethasone (VRd) for initial therapy of newly diagnosed multiple myeloma (NDMM): Results of ENDURANCE (E1A11) phase III trial. J Clin Oncol. 2020;38 (18_suppl):LBA3. https://doi.org/10.1200/JCO.2020.38.18_suppl.LBA3.

    Article  Google Scholar 

  35. 35.

    Moreau P, Hulin C, Macro M, Caillot D, Chaleteix C, Roussel M, et al. VTD is superior to VCD prior to intensive therapy in multiple myeloma: results of the prospective IFM2013-04 trial. Blood. 2016;127:2569–74. https://doi.org/10.1182/blood-2016-01-693580.

    CAS  Article  PubMed  Google Scholar 

  36. 36.

    Facon T, Kumar S, Plesner T, Orlowski RZ, Moreau P, Bahlis N, et al. Daratumumab plus lenalidomide and dexamethasone for untreated myeloma. N Engl J Med. 2019;380:2104–15. https://doi.org/10.1056/NEJMoa1817249.

    CAS  Article  PubMed  Google Scholar 

  37. 37.

    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 Off J Am Soc Clin Oncol. 2017;35:3279–89. https://doi.org/10.1200/JCO.2017.72.6679.

    CAS  Article  Google Scholar 

  38. 38.

    Benboubker L, Dimopoulos MA, Dispenzieri A, Catalano J, Belch AR, Cavo M, et al. Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma. N Engl J Med. 2014;371:906–17. https://doi.org/10.1056/NEJMoa1402551.

    CAS  Article  PubMed  Google Scholar 

  39. 39.

    Botta C, Ciliberto D, Rossi M, Staropoli N, Cuce M, Galeano T, et al. Network meta-analysis of randomized trials in multiple myeloma: efficacy and safety in relapsed/refractory patients. Blood Adv. 2017;1:455–66. https://doi.org/10.1182/bloodadvances.2016003905.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  40. 40.

    Siegel DS, Desikan KR, Mehta J, Singhal S, Fassas A, Munshi N, et al. Age is not a prognostic variable with autotransplants for multiple myeloma. Blood. 1999;93:51–54.

    CAS  Article  Google Scholar 

  41. 41.

    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;115:1873–9. https://doi.org/10.1182/blood-2009-09-241737.

    CAS  Article  PubMed  Google Scholar 

  42. 42.

    Muchtar E, Dingli D, Kumar S, Buadi FK, Dispenzieri A, Hayman SR, et al. Autologous stem cell transplant for multiple myeloma patients 70 years or older. Bone Marrow Transplant. 2016;51:1449–55. https://doi.org/10.1038/bmt.2016.174.

    CAS  Article  PubMed  Google Scholar 

  43. 43.

    Auner HW, Iacobelli S, Sbianchi G, Knol-Bout C, Blaise D, Russell NH, et al. Melphalan 140 mg/m(2) or 200 mg/m(2) for autologous transplantation in myeloma: results from the Collaboration to Collect Autologous Transplant Outcomes in Lymphoma and Myeloma (CALM) study. A report by the EBMT Chronic Malignancies Working Party. Haematologica. 2018;103:514–21. https://doi.org/10.3324/haematol.2017.181339.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We would like to acknowledge the Stanford BMT Database Management team.

Funding

Surbhi Sidana, MD was supported by KL2TR003143, KL2 Mentored Career Development Program, Stanford Clinical Translational Science Award Program.

Author information

Affiliations

Authors

Contributions

CL designed the study, collected and analyzed the data, and wrote the paper. SS designed the study, analyzed the data, and wrote the paper. LM, AR, RL, DI, JC, MF, LJ, ML, RN, WKW, EM, JS, PS, SA, and DM critically appraised the paper.

Corresponding author

Correspondence to Surbhi Sidana.

Ethics declarations

Conflict of interest

SS: Consultancy: Janssen. AR: Research Support, Pharmacyclics; one-time advisory boards for Nohla and Kaleido; expert witness, U.S. Department of Justice; brother employed by Johnson & Johnson.

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

Verify currency and authenticity via CrossMark

Cite this article

Lemieux, C., Muffly, L.S., Rezvani, A. et al. Outcomes with autologous stem cell transplant vs. non-transplant therapy in patients 70 years and older with multiple myeloma. Bone Marrow Transplant (2020). https://doi.org/10.1038/s41409-020-01026-7

Download citation

Search