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Use of eltrombopag in aplastic anemia in Europe

Annals of Hematology volume 98, pages 1341–1350 (2019)Cite this article

Abstract

Eltrombopag (ELT), an oral thrombopoietin receptor agonist, has recently emerged as a promising new drug for the treatment of aplastic anemia (AA). How ELT is used outside of clinical trials in the real-world setting and results of this treatment are not known. We conducted therefore a retrospective survey on the use of ELT in AA among EBMT member centers. We analyzed the 134 patients reported in our survey together with 46 patients recently published by Lengline et al. The median follow-up from start of ELT treatment was 15.3 months, with 85.6% patients alive at last follow-up. Importantly, only 28.9% of our patients received ELT according to the FDA/EMA label as monotherapy in the relapsed/refractory setting, whereas 16.7% received ELT upfront. The overall response rate in our cohort was 62%, very similar to the results of the pivotal ELT trial. In multivariate analysis, combination therapy with ELT/cyclosporine/ATG and response to previous therapy were associated with response. Overall survival was favorable with a 1-year survival from ELT start of 87.4%. We identified age, AA severity before ELT start and response to ELT as variables significantly associated with OS. Two patients transformed to MDS; other adverse events were mostly benign. In sum, ELT is used widely in Europe to treat AA patients, mostly in the relapsed/refractory setting. Response to ELT is similar to the clinical trial data across different age groups, treatment lines, and treatment combinations and results in favorable survival.

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Acknowledgements

We would like to thank all centers contributing patient data to the survey.

Author information

Affiliations

  1. Department of Hematology, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland

    Matyas Ecsedi, Beatrice Drexler & Jakob Passweg

  2. Hopital St. Louis, Paris, France

    Étienne Lengline & Régis Peffault de Latour

  3. EBMT Data Office, Leiden, Netherlands

    Cora Knol-Bout, Paul Bosman & Dirk-Jan Eikema

  4. First State Pavlov Medical University of St. Petersburg, St. Petersburg, Russia

    Boris Afanasyev

  5. Dimitri Rogachev Federal Research Center for Pediatric Hematology, Oncology and Immunology of Russian Federation, Moscow, Russia

    Alexei Maschan

  6. University of Heidelberg, Heidelberg, Germany

    Peter Dreger

  7. Leiden University Hospital, Leiden, Netherlands

    Constantijn J. M. Halkes

  8. Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, and University of Milan, Milan, Italy

    Agostino Cortelezzi

  9. Hôpital Emile Muller, Mulhouse, France

    Bernard Drénou

  10. Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy

    Andrea Patriarca

  11. S.S.C.V.D Trapianto di Cellule Staminali, Torino, Italy

    Benedetto Bruno

  12. Ospedale Civile, Pescara, Italy

    Daniela Onofrillo

  13. Institute Giannina Gaslini, Genoa, Italy

    Edoardo Lanino & Carlo Dufour

  14. University Hospital Center and Medical School, University of Zagreb, Zagreb, Croatia

    Drazen Pulanic & Ranka Serventi-Seiwerth

  15. Clinical Hematology, CHU Nantes, Nantes, France

    Alice Garnier

  16. Karolinska University Hospital, Stockholm, Sweden

    Per Ljungman

  17. S.Orsola-Malpighi Hospital, Bologna University, Bologna, Italy

    Francesca Bonifazi

  18. Fondazione Policlinico Universitario A. Gemelli-IRCCS, Rome, Italy

    Sabrina Giammarco

  19. CHU ESTAING, Clermont, France

    Olivier Tournilhac

  20. Ospedale San Gerardo, Monza, Italy

    Pietro Pioltelli

  21. Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

    Alicia Rovó

  22. Hematology, Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy

    Antonio M. Risitano

Authors
  1. Matyas Ecsedi
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  2. Étienne Lengline
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  3. Cora Knol-Bout
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  4. Paul Bosman
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  6. Boris Afanasyev
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  7. Alexei Maschan
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  8. Peter Dreger
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  9. Constantijn J. M. Halkes
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  10. Beatrice Drexler
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  11. Agostino Cortelezzi
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  12. Bernard Drénou
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  13. Andrea Patriarca
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  14. Benedetto Bruno
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  15. Daniela Onofrillo
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  16. Edoardo Lanino
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  17. Drazen Pulanic
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  18. Ranka Serventi-Seiwerth
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  19. Alice Garnier
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  20. Per Ljungman
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  21. Francesca Bonifazi
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  22. Sabrina Giammarco
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  23. Olivier Tournilhac
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  24. Pietro Pioltelli
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  25. Alicia Rovó
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  26. Antonio M. Risitano
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  27. Régis Peffault de Latour
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  28. Carlo Dufour
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  29. Jakob Passweg
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Consortia

for the EBMT SAA Working Party

Corresponding author

Correspondence to Jakob Passweg.

Ethics declarations

All procedures performed were in accordance with the ethical standards of the applicable institutional and national research committees, with the 1964 Helsinki declaration and its later amendments as well as comparable ethical standards. All patients provided informed consent to inclusion of their data in the EBMT SAA registry.

Conflict of interest

Francesca Bonifazi received speaker’s fees from Novartis. The other authors declare no conflicts of interest.

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Electronic supplementary material

Figure S1
figure 4

Competing risk analysis for response or death without response according to a) AA severity before ELT start, b) treatment line. (PNG 139 kb)

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Table S1

Baseline characteristics according to a) treatment line, b) ELT combination. (DOCX 15 kb)

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Ecsedi, M., Lengline, É., Knol-Bout, C. et al. Use of eltrombopag in aplastic anemia in Europe. Ann Hematol 98, 1341–1350 (2019). https://doi.org/10.1007/s00277-019-03652-8

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  • DOI: https://doi.org/10.1007/s00277-019-03652-8

Keywords

  • Aplastic anemia
  • Eltrombopag
  • Growth factors
  • Immunosuppression