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Romiplostim is effective for eltrombopag-refractory aplastic anemia: results of a retrospective study

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Abstract

Eltrombopag (EPAG) and romiplostim (ROM), thrombopoietin receptor-agonists with demonstrated efficacy against aplastic anemia (AA) in prospective controlled studies, were authorized in Japan for use in adults with aplastic anemia in 2017 and 2019, respectively. So far, no data are available on the potential contribution of switching from ROM to EPAG or vice versa in terms of efficacy or tolerance. Efficacies and tolerance profiles of ten patients, who failed to respond to the maximum dose of EPAG and then switched to ROM, were evaluated. All ten patients received a maximum dose of ROM (20 μg/kg/week). At a median follow-up of twelve months, seven of ten patients (70%) had achieved either neutrophil, erythroid, or platelet response, including one complete response. No patients showed platelet count fluctuations that were reported during ROM treatment for immune thrombocytopenia. In univariate analysis of the relationship between efficacy and demographics, the response had a correlation with neither factors. None of the patients stopped the ROM treatment because of adverse events. Although a larger number of patients and a longer follow-up period are needed to confirm our findings, our results show the efficacy of ROM in patients with EPAG-refractory AA.

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References

  1. Young NS. Aplastic anemia. N Engl J Med. 2018;379(17):1643–56.

    Article  CAS  Google Scholar 

  2. Otha A, Nagai M, Nishina M, Shimada N, Nakao S, Kurokawa M. Incidence of aplatic anemia in Japan: analysis of data from a nationwide registration system. Int J Epidemiol. 2015;44:i178.

    Google Scholar 

  3. Shin SH, Lee JW. The optimal immunosuppressive therapy for aplastic anemia 2013. Int J Hematol. 2013;97:564–72.

    Article  CAS  Google Scholar 

  4. Baciglupo A. How I treat acquired aplastic anemia. Blood. 2017;129(11):1428–36.

    Article  Google Scholar 

  5. Scheinberg P. Activity of eltrombopag in severe aplastic anemia. Blood Adv. 2018;2(21):3054–62.

    Article  CAS  Google Scholar 

  6. Olnes MJ, Scheinberg P, Calvo KR, Desmond R, Tang Y, Dumitriu B, et al. Eltrombopag and improved hematopoiesis in refractory aplastic anemia. N Engl J Med. 2012;367:11–9.

    Article  CAS  Google Scholar 

  7. Lengline E, Drenou B, Peterlin P, Tournilhac O, Abraham J, Berceanu A, et al. Nationwide survey on the use of eltrombopag in patients with severe aplastic anemia: a report on behalf of the French reference center for aplastic anemia. Haematol. 2018;103(2):212–20.

    Article  CAS  Google Scholar 

  8. Kaushansky K. Historical review: megakaryopoiesis and thrombopoiesis. Blood. 2008;111(3):981–6.

    Article  CAS  Google Scholar 

  9. Ghanima W, Cooper N, Rodeghiero F, Godeau B, Bussel JB. Thrombopietin receptor agonists: ten years later. Haematol. 2018;104(6):1112–23.

    Article  Google Scholar 

  10. Khellaf M, Viallard JF, Hamidou M, Cheze S, Roudot-Thoraval F, Lefrere F, et al. A retrospective pilot evaluation of switching thrombopoietic receptor-agonists in immune thrombocytopenia. Haematol. 2013;98(6):881–7.

    Article  CAS  Google Scholar 

  11. Zeigler FC, de Sauvage F, Widmer HR, Keller GA, Donahue C, Schreiber RD, et al. In vitro megakaryocytopoieteic and thrombopoietic activity of c-mpl ligand (TPO) on purified murine hematopoietic stem cells. Blood. 1994;84:4045–52.

    Article  CAS  Google Scholar 

  12. Erickson-Miller CL, Delorme E, Tian SS, Hopson CB, Landis AJ, El V, et al. Preclinical activity of eltrombopag (SB-497115), an oral, nonpeptide thrombopoietin receptor agonist. Stem Cells. 2009;27(2):424–30.

    Article  CAS  Google Scholar 

  13. Desmond R, Townsley DM, Dumitriu B, Olnes MJ, Scheinberg P, Bevans M, et al. Eltrombopag restores trilineage hematopoiesis in refractory severe aplastic anemia that can be sustained on discontinuation of drug. Blood. 2014;123(12):1818–25.

    Article  CAS  Google Scholar 

  14. Townsley DM, Scheinberg P, Winkler T, Desmond R, Dumitriu B, Rios O, et al. Eltrombopag added to standard immunosuppression for aplastic anemia. N Engl J Med. 2017;376:1540–50.

    Article  CAS  Google Scholar 

  15. Lee JW, Lee SE, Jung CW, Park S, Keta H, Park SK, et al. Romiplostim in patients with refractory aplastic anaemia previously treated with immunosuppressive therapy: a dose-finding and long-term treatment phase 2 trial. Lancet Haematol. 2019;6(11):e562–e572572.

    Article  Google Scholar 

  16. Drug label information of romiplostim in JAPAN. www.info.pmda.go.jp/go/pack/3999430D1024_1_06/?view=frame&style=XML&lang=ja Accessed May 1, 2020.

  17. Killick SB. Guidelines for the diagnosis and management of adult aplastic anaemia. Br J Haematol. 2016;172:187–207.

    Article  Google Scholar 

  18. Common Terminology Criteria for Adverse Events (CTCAE) v5.0. 2017. https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_5x7.pdf Accessed May 1, 2020.

  19. Kanda Y. Investigation of the freely available easy-to-use software “EZR” for medical statistics. Bone Marrow Transplant. 2013;48(3):452–8.

    Article  CAS  Google Scholar 

  20. Winkler T, Fan X, Cooper J, Desmond R, Young DJ, Townsley DM, et al. Treatment optimization and genomic outcomes in refractory severe aplastic anemia treated with eltrombopag. Blood. 2019;133(24):2575–85.

    Article  CAS  Google Scholar 

  21. Julian MJ, Daphne W, Yanli D, Joanne U, Valerie K, David C, et al. Phase 1 clinical study of eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist. Blood. 2007;109:4739–41.

    Article  Google Scholar 

  22. Shida Y, Takahashi N, Nohda S, Hirama T. Pharmacokinetics and pharmacodynamics of eltrombopag in healthy Japanese males. Jpn J Clin Pharmacol Ther. 2011;42(1):11–20.

    Article  CAS  Google Scholar 

  23. Gill H, Leung GMK, Lopes D, Kwong YL. The thrombopoietin mimetics eltrombopag and romiplostim in the treatment of refractory aplastic anaemia. Br J Haematol. 2017;176:984–99.

    Article  Google Scholar 

  24. Gibiansky E, Zhang J, Williams D, Wang Z, Ouellet D. Population pharmacokinetics of eltrombopag in healthy subjects and patients with chronic idiopathic thrombocytopenic purpura. J Clin Pharmacol. 2011;51(6):842–56.

    Article  CAS  Google Scholar 

  25. Kuter DJ, Macahilig C, Grotzinger KM, Poston SA, Wang PF, Dawson KL, et al. Treatment patterns and clinical outcomes in patients with chronic immune thrombocytopenia(ITP) switched to eltrombopag or romiplostim. Int J Hematol. 2015;101:255–63.

    Article  CAS  Google Scholar 

  26. Vlachodimitropoulou E, Chen YL, Garbowski M, Koonyosying P, Psaila B, Sola-Visner M, et al. Eltrombopag: a powerful chelator of cellular or extracellular iron(III) alone or combined with a second chelator. Blood. 2017;130(17):1923–33.

    Article  CAS  Google Scholar 

  27. Roth M, Will B, Simkin G, Narayanagari S, Barreyro L, Bartholdy B, et al. Eltrombopag inhibits the proliferation of leukemia cells via reduction of intracellular iron and induction of differentiation. Blood. 2012;120(2):386–94.

    Article  CAS  Google Scholar 

  28. Gonzalez-Porras JR, Mingot-Castellano ME, Andrade MM, Alonso R, Caparros I, Arratibel MC, et al. Use of eltrombopag after romiplstim in primary immune thrombocytopenia. Br J Haematol. 2015;169(1):111–6.

    Article  CAS  Google Scholar 

  29. Cantoni S, Carpenedo M, Mazzucconi MG, De Stefano V, Carrai V, Ruggeri M, et al. Alternate use of thrombopoietin receptor agonists in adult primary immune thrombocytopenia patients: a retrospective collaborative survey from Italian hematology centers. Am J Hematol. 2018;93(1):58–64.

    Article  CAS  Google Scholar 

  30. Yan XQ, Lacey D, Hill D, Chen Y, Fletcher F, Hawley RG, et al. A model of myelofibrosis and osteosclerosis in mice induced by overexpressing thrombopoietin (mpl ligand): reversal of disease by bone marrow transplantation. Blood. 1996;88(2):402–9.

    Article  CAS  Google Scholar 

  31. Zhao LP, De Fontbrune FS, Contejean A, Abraham J, Terriou L, Cecile C, et al. Nationwide survey in France on the use of romiplostim in patients with refractory severe aplastic anemia. Bone Marrow Transplant. 2019;54:1161–3.

    Article  Google Scholar 

  32. Bussel JB, Kuter DJ, Pullarkat V, Lyons RM, Guo M, Nichol JL. Safety and efficacy of long-term treatment with romiplostim in thrombocytopenic patients with chronic ITP. Blood. 2009;113(10):2161–71.

    Article  CAS  Google Scholar 

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Acknowledgments

The authors would like to thank Editage (www.editage.com) for English language editing.

Funding

The Practical Research for Innovative Cancer Control from the Japan Agency for Medical Research and Development, AMED (19ck0106251h0003): Establishment of molecular-based risk-stratification system in acute myeloid leukemia and confirmation of its practical application and usefulness in clinics.

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Authors and Affiliations

  1. Department of Hematology, NTT Medical Center Tokyo, 5-9-22 Higashigotanda, Shinagawa-ku, Tokyo, 141-8625, Japan

    Masataka Ise, Hiromitsu Iizuka, Yoshimasa Kamoda, Masako Hirao, Michiko Kida & Kensuke Usuki

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  1. Masataka Ise
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  2. Hiromitsu Iizuka
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  3. Yoshimasa Kamoda
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  4. Masako Hirao
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  5. Michiko Kida
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  6. Kensuke Usuki
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Correspondence to Kensuke Usuki.

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Conflict of interest

Kensuke Usuki has received research funding from Astellas Pharma Inc., Alexion Pharmaceuticals, AbbVie GK, Gilead, SymBio Pharmaceuticals Ltd., Daiichi Sankyo Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Chugai Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Novartis Pharma K.K., Bristol-Myers Squibb Company, Ono Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K., Celgene Corporation, Takeda Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Mundipharma K.K., Astellas-Amgen-Biopharma KK, Apellis Pharmaceuticals Inc, Nippon Shinyaku Co., Ltd., Kyowa Kirin Co., Ltd., and Pfizer Japan Inc., and has served on speakers bureaus for Novartis Pharma K.K., Alexion Pharmaceuticals, Eisai Co., Ltd., Ono Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., MSD K.K., Otsuka Pharmaceutical Co., Ltd., SymBio Pharmaceuticals Ltd., Celgene Corporation, Daiichi Sankyo Co., Ltd., Takeda Pharmaceutical Co., Ltd., Nippon Shinyaku Co., Ltd., PharmaEssentia Corp., Bristol-Myers Squibb Company, and Yakult Honsha Co. Ltd.

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Ise, M., Iizuka, H., Kamoda, Y. et al. Romiplostim is effective for eltrombopag-refractory aplastic anemia: results of a retrospective study. Int J Hematol 112, 787–794 (2020). https://doi.org/10.1007/s12185-020-02971-1

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  • DOI: https://doi.org/10.1007/s12185-020-02971-1

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