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Multiple myeloma, gammopathies

Early myeloma-related death in elderly patients: development of a clinical prognostic score and evaluation of response sustainability role

Leukemia volume 32, pages 2427–2434 (2018)Cite this article

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A Correction to this article was published on 08 March 2019

This article has been updated

Abstract

Although survival of elderly myeloma patients has significantly improved there is still a subset of patients who, despite being fit and achieving optimal responses, will die within 2 years of diagnosis due to myeloma progression. The objective of this study was to define a scoring prognostic index to identify this group of patients. We have evaluated the outcome of 490 newly diagnosed elderly myeloma patients included in two Spanish trials (GEM2005-GEM2010). Sixty-eight patients (13.8%) died within 2 years of diagnosis (early deaths) due to myeloma progression. Our study shows that the use of simple scoring model based on 4 widely available markers (elevated LDH, ISS 3, high risk CA or >75 years) can contribute to identify up-front these patients. Moreover, unsustained response (<6 months duration) emerged as one important predictor of early myeloma-related mortality associated with a significant increase in the risk of death related to myeloma progression. The identification of these patients at high risk of early death is relevant for innovative trials aiming to maintain the depth of first response, since many of them will not receive subsequent lines of therapy.

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  • 08 March 2019

    Following the publication of this article, the author notes that the following information was missed from the acknowledgments section: This study wassupported by the Cooperative Research Thematic Networkgrants RD12/0036/0058 and RD12/0036/0046 of the Redde Cancer (Cancer Network of Excellence); Instituto deSalud Carlos III, Spain, Instituto de Salud Carlos III/SubdirecciónGeneral de Investigación Sanitaria part-financedby the European Regional Development Fund (FIS: PI12/01761; PI12/02311; PI13/01469; PI14/01867, G03/136;Sara Borrell: CD13/00340); Asociación Española Contra elCáncer (GCB120981SAN) and FEDER.The authors wish to apologise for any inconveniencecaused.

  • 08 March 2019

    Following the publication of this article, the author notes that the following information was missed from the acknowledgments section:

References

  1. 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;111:2516–20.

    Article  CAS  Google Scholar 

  2. 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 

  3. San Miguel JF, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, Kropff M, et al. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med. 2008;359:906–17.

    Article  CAS  Google Scholar 

  4. 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.

    Article  CAS  Google Scholar 

  5. San Miguel JF, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, Kropff M, et al. Persistent overall survival benefit and no increased risk of second malignancies with bortezomib-melphalan-prednisone versus melphalan-prednisone in patients with previously untreated multiple myeloma. J Clin Oncol. 2013;31:448–55.

    Article  CAS  Google Scholar 

  6. Facon TDM, Dispenzieri A, Catalano JV, Belch A, Cavo M, Pinto A, Weisel K, Ludwig H, Bahlis NJ, Banos A, Tiab M, Delforge M, Cavenagh JD, Geraldes C, Lee J, Chen C, Oriol A, De La Rubia J, White D, Binder D, Lu J, Anderson KC, Moreau P, Attal M, Fermand JP, Avet-Loiseau H, Ervin-Haynes A, Chen G, Houck V, Hulin C, Benboubker L. Final analysis of overall survival from the first trial. Blood. 2016;128:241.

    Google Scholar 

  7. Moreau P, Cavo M, Sonneveld P, Rosinol L, Attal M, Pezzi A, et al. Combination of international scoring system 3, high lactate dehydrogenase, and t(4;14) and/or del(17p) identifies patients with multiple myeloma (MM) treated with front-line autologous stem-cell transplantation at high risk of early MM progression-related death. J Clin Oncol. 2014;32:2173–80.

    Article  CAS  Google Scholar 

  8. Larocca A, Palumbo A. How I treat fragile myeloma patients. Blood. 2015;126:2179–85.

    Article  CAS  Google Scholar 

  9. Palumbo A, Bringhen S, Mateos MV, Larocca A, Facon T, Kumar SK, et al. Geriatric assessment predicts survival and toxicities in elderly myeloma: an International Myeloma Working Group report. Blood. 2015;125:2068–74.

    Article  CAS  Google Scholar 

  10. 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 

  11. 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;33:2863–9.

    Article  CAS  Google Scholar 

  12. Barlogie B, Anaissie E, Haessler J, van Rhee F, Pineda-Roman M, Hollmig K, et al. Complete remission sustained 3 years from treatment initiation is a powerful surrogate for extended survival in multiple myeloma. Cancer. 2008;113:355–9.

    Article  Google Scholar 

  13. Paiva B, Gutierrez NC, Rosinol L, Vidriales MB, Montalban MA, Martinez-Lopez J, et al. High-risk cytogenetics and persistent minimal residual disease by multiparameter flow cytometry predict unsustained complete response after autologous stem cell transplantation in multiple myeloma. Blood. 2012;119:687–91.

    Article  CAS  Google Scholar 

  14. Yong K, Delforge M, Driessen C, Fink L, Flinois A, Gonzalez-McQuire S, et al. Multiple myeloma: patient outcomes in real-world practice. Br J Haematol. 2016;175:252–64.

    Article  Google Scholar 

  15. Robert A, Kyle on behalf of the 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 

  16. Mateos MV, Oriol A, Martinez-Lopez J, Gutierrez N, Teruel AI, de Paz R, et al. Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myeloma: a randomised trial. Lancet Oncol. 2010;11:934–41.

    Article  CAS  Google Scholar 

  17. Mateos MV, Martinez-Lopez J, Hernandez MT, Ocio EM, Rosinol L, Martinez R, et al. Sequential vs alternating administration of VMP and Rd in elderly patients with newly diagnosed MM. Blood. 2016;127:420–5.

    Article  CAS  Google Scholar 

  18. Gutierrez NC, Castellanos MV, Martin ML, Mateos MV, Hernandez JM, Fernandez M, et al. Prognostic and biological implications of genetic abnormalities in multiple myeloma undergoing autologous stem cell transplantation: t(4;14) is the most relevant adverse prognostic factor, whereas RB deletion as a unique abnormality is not associated with adverse prognosis. Leukemia. 2007;21:143–50.

    Article  CAS  Google Scholar 

  19. Lopez-Corral L, Gutierrez NC, Vidriales MB, Mateos MV, Rasillo A, Garcia-Sanz R, et al. The progression from MGUS to smoldering myeloma and eventually to multiple myeloma involves a clonal expansion of genetically abnormal plasma cells. Clin Cancer Res. 2011;17:1692–1700.

    Article  CAS  Google Scholar 

  20. 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.

    Article  CAS  Google Scholar 

  21. Harrell FE Jr., Lee KL, Mark DB. Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Stat Med. 1996;15:361–87.

    Article  Google Scholar 

  22. Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J. Am. Stat. Assoc. 2012;94:446, 496–509

    Google Scholar 

  23. Mateos MV, Oriol A, Martinez-Lopez J, Gutierrez N, Teruel AI, Lopez de la Guia A, et al. Maintenance therapy with bortezomib plus thalidomide or bortezomib plus prednisone in elderly multiple myeloma patients included in the GEM2005MAS65 trial. Blood. 2012;120:2581–8.

    Article  CAS  Google Scholar 

  24. Mateos MV, Oriol A, Martinez-Lopez J, Teruel AI, Lopez de la Guia A, Lopez J, et al. GEM2005 trial update comparing VMP/VTP as induction in elderly multiple myeloma patients: do we still need alkylators? Blood. 2014;124:1887–93.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Jorge Nuñez for the statistical review of the present work.

Author contributions

P.R.O., M.-V.M., and J.S.-M. were involved in the conception and design of the study and writing of the manuscript. P.R.O. and N.M.-C. did the statistical analysis. M.-V.M and J.S.-M. were principal investigators of both trials and were involved in the original design of the study, writing of the protocol, analyzing and interpreting the data. All the authors were involved in patient recruitment and reviewed and approved the paper.

Author information

Author notes

  1. These authors contributed equally: Paula Rodríguez-Otero, María Victoria Mateos.

Authors and Affiliations

  1. Clínica Universidad de Navarra, CIMA, IDISNA, CIBERONC, Pamplona, Spain

    Paula Rodríguez-Otero, Bruno Paiva & Jesús F. San Miguel

  2. Complejo Asistencial Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain

    María Victoria Mateos, Enrique M. Ocio, Norma C. Gutiérrez & Noemí Puig

  3. Hospital Universitario 12 de Octubre, Instituto de Investigación 12 de Octubre, CIBERONC, Madrid, Spain

    Joaquín Martínez-López & María Teresa Cedena

  4. Preventive Medicine and Public Health Department, University of Navarra, Pamplona, Spain

    Nerea Martín-Calvo & Juan José Lahuerta

  5. Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain

    Miguel-Teodoro Hernández

  6. Hospital Clinic I Provincial, Institu d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    Laura Rosiñol & Joan Bladé

  7. Hospital Clínico San Carlos, Madrid, Spain

    Rafael Martínez

  8. Hospital Clínico de Valencia, Valencia, Spain

    Ana-Isabel Teruel

  9. Hospital Son Llatzer, Palma de Mallorca, Spain

    Joan Bargay

  10. Hospital de Donostia, San Sebastian, Spain

    Enrique Bengoechea

  11. Institut d’Oncologia Dr. Josep Trueta, Girona, Spain

    Yolanda González

  12. Hospital de Madrid Sanchinarro, Universidad CEU San Pablo, Madrid, Spain

    Jaime Pérez de Oteyza

  13. Hospital Vall d’Hebron, Barcelona, Spain

    Mercedes Gironella

  14. Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain

    Cristina Encinas

  15. Hospital General Virgen del Rocío, Sevilla, Spain

    Jesús Martín

  16. Hospital San Pedro de Alcántara, Cáceres, Spain

    Carmen Cabrera

  17. Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain

    Luis Palomera

  18. Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, IMIB-Arrixaca, Universidad de Murcia, Murcia, Spain

    Felipe de Arriba

  19. Insitut Català d’Oncologia, Institut Josep Carreras, Hospital German Trias i Pujol, Badalona, Barcelona, Spain

    Albert Oriol

Authors
  1. Paula Rodríguez-Otero
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  2. María Victoria Mateos
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  22. Bruno Paiva
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  24. Albert Oriol
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  27. Jesús F. San Miguel
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Corresponding author

Correspondence to Jesús F. San Miguel.

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Conflict of interest

P.R.-O.: has served on the speaker’s bureau and as a member of advisory boards for Janssen and Celgene. M.-V.M.: has declared consultancy for: Janssen, Celgene, Takeda, Amgen. E.-M.O.: has declared consultancy for or honoraria from: Mundipharma, Celgene, Amgen, Novartis, Takeda, AbbVie, BMS, Janssen. B.P.: has declared grants and personal fees from Celgene, Janssen, Takeda, Sanofi, BMS and personal fees from Amgen and grants from Engmab. J.S.-M.: received honoraria as part of Advisory boards from Celgene, Novartis, Millenium, Janssen, Amgen, MSD, Sanofi, and BMS. A.O.: has served as a member of advisory boards for Janssen and Celgene. J.B.: received honoraria for lectures and advisory boards from Celgene and Janssen and grant support from Janssen. L.R.: received honoraria grom Janssen and Celgene. The remaining authors declare that they have no conflict of interest.

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Rodríguez-Otero, P., Mateos, M.V., Martínez-López, J. et al. Early myeloma-related death in elderly patients: development of a clinical prognostic score and evaluation of response sustainability role. Leukemia 32, 2427–2434 (2018). https://doi.org/10.1038/s41375-018-0072-6

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