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Annals of Hematology

, Volume 98, Issue 3, pp 705–711 | Cite as

Study of the frequency and reasons for discontinuation of different lines of treatment in patients with multiple myeloma

  • Alicia SenínEmail author
  • Francesc García-Pallarols
  • Randa Ben Azaiz
  • Laia Martínez-Serra
  • Sara Montesdeoca
  • David Román
  • Mariana Ferraro
  • Ivonne Párraga
  • Carlos Besses
  • Eugenia Abella
Original Article

Abstract

The availability of new agents for the treatment of multiple myeloma has allowed the use of multiple lines of treatment, but a percentage of patients do not reach to receive this combination because of toxicity and early death. In this regard, a cross-sectional European study evaluated the management of different lines and discontinuation of treatment in 7635 patients from seven countries in routine clinical practice, finding that 39% of European patients do not receive a second line and that only 4% of patients reach third line in Spain, a figure that is striking when comparing with the rest of the countries. We analyze the frequency and causes of treatment discontinuation in a series of 108 patients from a Spanish University hospital showing that the main reason for permanent treatment discontinuation after finishing first line was to have a response, while death due to disease progression accounted for the main reason in subsequent lines of therapy, with its frequency increasing according to the number of lines received. Additionally, in our longitudinal study, we estimated, using a competitive risk analysis, that 22% of patients would not receive a second line of therapy at 60 months and 47% would not reach third line, also at 60 months, showing a marked discrepancy with the results reported in the cross-sectional European study. Although based on limited data, our results suggest the convenience of validating the findings of cross-sectional studies conducted in large cohorts.

Keywords

Multiple myeloma Lines of treatment Discontinuation Competitive risk analysis 

Notes

Authors contribution

AS, EA, RBL, and FG-P designed the study, collected data, performed the statistical analysis, and wrote the manuscript. All authors reviewed and approved the final version of the manuscript.

Funding information

Alicia Senín received the support of a SEHH grant for the development of this study 2015-2017.

Compliance with ethical standards

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent was obtained from all patients for being included in the study.

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    San Miguel J, Weisel K, Moreau P, Lacy M, Song K, Delforge M, Karlin L, Goldschmidt H, Banos A, Oriol A, Alegre A, Chen C, Cavo M, Garderet L, Ivanova V, Martinez- Lopez J, Belch A, Palumbo A, Schey S, Sonneveld P, Yu X, Sternas L, Jacques C, Zaki M, Dimopoulos M (2013) Pomalidomide plus low dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial. Lancet Oncol 14:1055–1066CrossRefGoogle Scholar
  2. 2.
    Stewart AK, Rajkumar SV, Dimopoulos MA, Masszi T, Spicka I, Oriol A, Hajek R, Rosinol L, Siegel DS, Mihaylov GG, Goranova-Marinova V, Rajnics P, Suvorov A, Niesvizky R, Jakubowiak AJ, San-Miguel JF, Ludwig H, Wang M, Maisnar V, Minarik J, Bensinger WI, Mateos MV, Ben-Yehuda D, Kukreti V, Zojwalla N, Tonda ME, Yang X, Xing B, Moreau P, Palumbo A (2015) Carfilzomib, lenalidomide and dexamethasone for relapsed multiple myeloma. N Engl J Med 372:142–152CrossRefGoogle Scholar
  3. 3.
    Usmani SZ, Weiss BM, Plesner T, Bahlis NJ, Belch A, Lonial S, Lokhorst HM, Voorhees PM, Richardson PG, Chari A, Sasser AK, Axel A, Feng H, Uhlar CM, Wang J, Khan I, Ahmadi T, Nahi H (2016) Clinical efficacy of daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma. Blood 128:37–44CrossRefGoogle Scholar
  4. 4.
    Cook G, Zweegman S, Mateos MV, Suzan F, Moreau P (2018) A question of class: treatment options for patients with relapsed and/or refractory multiple myeloma. Crit Rev Oncol Hematol 121:74–89CrossRefGoogle Scholar
  5. 5.
    Cavo M, Terpos E, Bargay J, Einsele H, Cavet J, Greil R, de Wit E (2018) The multiple myeloma treatment landscape: international guideline recommendations and clinical practice in Europe. Expert Rev Hematol 11(3):219–237CrossRefGoogle Scholar
  6. 6.
    Moreau, P, San Miguel, J, Ludwig, H, Schouten, H, Mohty, M, Dimopoulos, M, Dreyling, M. ESMO Guidelines Working Group. Multiple myeloma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013; 24 Suppl 6: vi133-7Google Scholar
  7. 7.
    Raab MS, Cavo M, Delforge M, Driessen C, Fink L, Flinois A, Gonzalez-McQuire S, Safaei R, Karlin L, Mateos MN, Schoen P, Yong K (2016) Multiple myeloma: practice patterns across Europe. Br J Haematol 175:66–76CrossRefGoogle Scholar
  8. 8.
    Yong K, Delforge M, Driessen C, Fink L, Flinois A, Gonzalez-McQuire S, Safaei R, Karlin L, Mateos MV, Raab MS, Schoen P, Cavo M (2016) Multiple myeloma: patient outcomes in real-world practice. Br J Haematol 175(2):252–264CrossRefGoogle Scholar
  9. 9.
    Coviello V, Boggess M (2018) Cumulative incidence estimation in the presence of competing risks. Stata J 4:103–112CrossRefGoogle Scholar
  10. 10.
    Allignol A, Schumacher M, Beyersmann J (2011) Empirical transition matrix of multi-state models: the etm package. J Stat Softw 38(4):1–15 URL http://www.jstatsoft.org/v38/i04/ CrossRefGoogle Scholar
  11. 11.
    R Core Team (2016) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna URL https://www.R-project.org/ Google Scholar
  12. 12.
    Greipp PR, San Miguel J, Durie BG et al (2005) International staging system for multiple myeloma. J Clin Oncol 23:3412–3420CrossRefGoogle Scholar
  13. 13.
    Palumbo A, Avet-Loiseau H, Oliva S, Lokhorst HM, Goldschmidt H, Rosinol L, Richardson P, Caltagirone S, Lahuerta JJ, Facon T, Bringhen S, Gay F, Attal M, Passera R, Spencer A, Offidani M, Kumar S, Musto P, Lonial S, Petrucci MT, Orlowski RZ, Zamagni E, Morgan G, Dimopoulos MA, Durie BGM, Anderson KC, Sonneveld P, San Miguel J, Cavo M, Rajkumar SV, Moreau P (2015) Revised international staging system for multiple myeloma: a report from International Myeloma Working Group. J Clin Oncol 33:2863–2869CrossRefGoogle Scholar
  14. 14.
    Ross FM, Avet-Loiseau H, Ameye G, Gutierrez NC, Liebisch P, O'Connor S, Dalva K, Fabris S, Testi AM, Jarosova M, Hodkinson C, Collin A, Kerndrup G, Kuglik P, Ladon D, Bernasconi P, Maes B, Zemanova Z, Michalova K, Michau L, Neben K, Hermansen NEU, Rack K, Rocci A, Protheroe R, Chiecchio L, Poirel HA, Sonneveld P, Nyegaard M, Johnsen HE, on behalf of the European Myeloma Network (2012) European Myeloma Network. Report from the European Myeloma Network on interphase FISH in multiple myeloma and related disorders. Haematologica 97(8):1272–1277CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Alicia Senín
    • 1
    Email author
  • Francesc García-Pallarols
    • 1
  • Randa Ben Azaiz
    • 1
  • Laia Martínez-Serra
    • 1
  • Sara Montesdeoca
    • 1
  • David Román
    • 1
  • Mariana Ferraro
    • 1
  • Ivonne Párraga
    • 1
  • Carlos Besses
    • 1
  • Eugenia Abella
    • 1
  1. 1.Hematology Department, Hospital del Mar-IMIM (Institut Hospital del Mar d’Investigacions Mèdiques)Universidad Autónoma de BarcelonaBarcelonaSpain

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