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Efficiency and safety of eltrombopag for multi-line failed Chinese patients with immune thrombocytopenia: cases with decreased megakaryocyte response well from single-center experience

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Abstract

Immune thrombocytopenia (ITP) was defined using the International Consensus Guidelines as a platelet count <100×109/L in the absence of other causes or disorders that may be associated with thrombocytopenia. For patients without response to first-line treatment or refractory, TPO receptor agonist (RA) is an ideal choice. This study was to evaluate the efficiency and safety of eltrombopag for multi-line failed Chinese patients with immune thrombocytopenia (ITP) and analyze the possible factors that may contribute to the differences based on personal characteristics. Thirty-five multi-line failed ITP patients who received eltrombopag treatment were enrolled retrospectively at the First Affiliated Hospital of Zhejiang Chinese Medical University from January 2018 to August 2020. The general information, peripheral hemogram changes, count of bone marrow megakaryocyte (MK), peripheral T cell subsets were recorded, the response, and adverse effects, was evaluated. Results showed that the overall, complete, and partial response rates were 54.3% (n=19), 48.6% (n=17), and 5.7% (n=2) respectively to eltrombopag in our center. The overall response rate of patients with decreased MK was 70%, which was unexpectedly higher than that of the patient with increased or normal MK count (52.9% and 40%, respectively). For patients with poorer eltrombopag response group, more NK cells were found in peripheral blood, and the patient with decreased MK have a higher level of T helper (Th) cells and regulatory T (Treg) cells. Nine eltrombopag-related adverse events were reported, and most commonly were upper respiratory tract infection (8.6%), elevated alanine transaminase (ALT, 5.7%), and venous thrombosis (5.7%). In conclusion, this study revealed that ITP patients with decreased megakaryocyte respond well to eltrombopag, and the abnormality of NK cells may play a role in patients with a poor eltrombopag response.

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References

  1. Lambert MP, Gernsheimer TB. Clinical updates in adult immune thrombocytopenia. Blood. 2017;129(21):2829–35.

    Article  CAS  Google Scholar 

  2. Audia S, Mahévas M, Samson M, Godeau B, Bonnotte B. Pathogenesis of immune thrombocytopenia. Autoimmun Rev. 2017;16(6):620–32. https://doi.org/10.1016/j.autrev.2017.04.012.

  3. Cuker A. Transitioning patients with immune thrombocytopenia to second-line therapy: challenges and best practices. Am J Hematol. 2018;93(6):816–23. https://doi.org/10.1002/ajh.25092.

  4. Neunert C, Terrell DR, Arnold DM, et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv. 2019;3(23):3829–66.

    Article  CAS  Google Scholar 

  5. Chaturvedi S, Arnold DM, McCrae KR. Splenectomy for immune thrombocytopenia: down but not out. Blood. 2018;131(11):1172–82. https://doi.org/10.1182/blood-2017-09-742353.

  6. Ghanima W, Khelif A, Waage A, Michel M, Tjønnfjord GE, Romdhan NB, et al. Rituximab as second-line treatment for adult immune thrombocytopenia (the RITP trial): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2015;385(9978):1653–61. https://doi.org/10.1016/S0140-6736(14)61495-1.

  7. Patel VL, Mahévas M, Lee SY, Stasi R, Cunningham-Rundles S, Godeau B, et al. Outcomes 5 years after response to rituximab therapy in children and adults with immune thrombocytopenia. Blood. 2012;119(25):5989–95. https://doi.org/10.1182/blood-2011-11-393975.

  8. Chugh S, Darvish-Kazem S, Lim W, Crowther MA, Ghanima W, Wang G, et al. Rituximab plus standard of care for treatment of primary immune thrombocytopenia: a systematic review and meta-analysis. Lancet Haematol. 2015;2(2):e75–81. https://doi.org/10.1016/S2352-3026(15)00003-4.

  9. Garnock-Jones KP, Keam SJ. Eltrombopag. Drugs. 2009;69(5):567–76.

    Article  CAS  Google Scholar 

  10. Thrombosis, Hemostasis Group CSoHCMA. Chinese guideline on the diagnosis and management of adult primary immune thrombocytopenia (version 2020). Zhonghua Xue Ye Xue Za Zhi. 2020;41(8):617–23.

    Google Scholar 

  11. Bussel JB, Provan D, Shamsi T, et al. Effect of eltrombopag on platelet counts and bleeding during treatment of chronic idiopathic thrombocytopenic purpura: a randomised, double-blind, placebo-controlled trial. Lancet. 2009;373(9664):641–8.

    Article  CAS  Google Scholar 

  12. Cekdemir D, Guvenc S, Ozdemirkiran F, et al. A multi-center study on the efficacy of eltrombopag in management of refractory chronic immune thrombocytopenia: a real-life experience. Turk J Haematol. 2019;36(4):230–7.

    PubMed  PubMed Central  Google Scholar 

  13. Fattizzo B, Levati G, Cassin R, Barcellini W. Eltrombopag in immune thrombocytopenia, aplastic anemia, and myelodysplastic syndrome: from megakaryopoiesis to immunomodulation. Drugs. 2019;79(12):1305–19. https://doi.org/10.1007/s40265-019-01159-0.

  14. Zhen C, Guo F, Fang X, Liu Y, Wang X. A family with distal myopathy with rimmed vacuoles associated with thrombocytopenia. Neurol Sci. 2014;35(9):1479–81.

    Article  Google Scholar 

  15. Liu XG, Bai XC, Chen FP, et al. Chinese guidelines for treatment of adult primary immune thrombocytopenia. Int J Hematol. 2018;107(6):615–23.

    Article  Google Scholar 

  16. Giordano P, Lassandro G, Barone A, Cesaro S, Fotzi I, Giona F, et al. Use of eltrombopag in children with chronic immune thrombocytopenia (ITP): a real life retrospective multicenter experience of the Italian Association of Pediatric Hematology and Oncology (AIEOP). Front Med (Lausanne). 2020;7:66. https://doi.org/10.3389/fmed.2020.00066.

  17. Ozdemirkiran F, Payzin B, Kiper HD, et al. Eltrombopag for the treatment of immune thrombocytopenia: the aegean region of Turkey experience. Turk J Haematol. 2015;32(4):323–8.

    Article  CAS  Google Scholar 

  18. Wong RSM, Saleh MN, Khelif A, et al. Safety and efficacy of long-term treatment of chronic/persistent ITP with eltrombopag: final results of the EXTEND study. Blood. 2017;130(23):2527–36.

    Article  CAS  Google Scholar 

  19. Al-Samkari H, Kuter DJ. Thrombopoietin level predicts response to treatment with eltrombopag and romiplostim in immune thrombocytopenia. Am J Hematol. 2018;93(12):1501–8.

    Article  CAS  Google Scholar 

  20. Fattizzo B, Pasquale R, Carpenedo M, et al. Bone marrow characteristics predict outcome in a multicenter cohort of primary immune thrombocytopenia patients treated with thrombopoietin analogs. Haematologica. 2019;104(10):e470–3.

    Article  CAS  Google Scholar 

  21. Drexler B, Passweg J. Current evidence and the emerging role of eltrombopag in severe aplastic anemia. Ther Adv Hematol. 2021;12:2040620721998126.

    Article  CAS  Google Scholar 

  22. Swinkels M, Rijkers M, Voorberg J, Vidarsson G, Leebeek FWG, Jansen AJG. Emerging concepts in immune thrombocytopenia. Front Immunol. 2018;9:880.

    Article  Google Scholar 

  23. Neunert C, Noroozi N, Norman G, et al. Severe bleeding events in adults and children with primary immune thrombocytopenia: a systematic review. J Thromb Haemost. 2015;13(3):457–64.

    Article  CAS  Google Scholar 

  24. Olsson B, Andersson PO, Jernas M, et al. T-cell-mediated cytotoxicity toward platelets in chronic idiopathic thrombocytopenic purpura. Nat Med. 2003;9(9):1123–4.

    Article  CAS  Google Scholar 

  25. Monzon Manzano E, Alvarez Roman MT, Justo Sanz R, et al. Platelet and immune characteristics of immune thrombocytopaenia patients non-responsive to therapy reveal severe immune dysregulation. Br J Haematol. 2020;189(5):943–53.

    Article  CAS  Google Scholar 

  26. Zufferey A, Kapur R, Semple JW. Pathogenesis and therapeutic mechanisms in immune thrombocytopenia (ITP). J Clin Med. 2017;6(2)16. https://doi.org/10.3390/jcm6020016.

  27. Wu D, Liu Y, Pang N, et al. PD-1/PD-L1 pathway activation restores the imbalance of Th1/Th2 and treg/Th17 cells subtypes in immune thrombocytopenic purpura patients. Medicine (Baltimore). 2019;98(43):e17608.

    Article  CAS  Google Scholar 

  28. Alvarado LJ, Huntsman HD, Cheng H, et al. Eltrombopag maintains human hematopoietic stem and progenitor cells under inflammatory conditions mediated by IFN-gamma. Blood. 2019;133(19):2043–55.

    Article  CAS  Google Scholar 

  29. Wang S, Liu F, Zhao H. Eosinophil granulocyte and NK cell-mediated platelet destruction in immune thrombocytopenia. Indian J Hematol Blood Transfus. 2018;34(1):121–4.

    Article  CAS  Google Scholar 

  30. Ebbo M, Audonnet S, Grados A, et al. NK cell compartment in the peripheral blood and spleen in adult patients with primary immune thrombocytopenia. Clin Immunol. 2017;177:18–28.

    Article  CAS  Google Scholar 

  31. Molinari A, Banov L, Bertamino M, et al. A practical approach to the use of low molecular weight heparins in VTE treatment and prophylaxis in children and newborns. Pediatr Hematol Oncol. 2015;32(1):1–10.

    Article  CAS  Google Scholar 

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Acknowledgements

We thank all the patients who gave consent to disclose their medical records and answered our review calls.

Funding

The present study was supported by National Natural Science Foundation of China (NO. 82174138, 81603573), Zhejiang Scientific Research Fund of Traditional Chinese Medicine (NO. 2020ZB085), and Zhejiang Outstanding Young Talent Fund of Traditional Chinese Medicine (NO. 2015ZQ012).

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Authors and Affiliations

  1. The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China

    Qi Liu, Yingying Shen, Yuzhu Li, Huijin Hu, Wenbin Liu, Yuechao Zhao, Huijie Dong, Yiping Shen, Yuhong Zhou, Baodong Ye & Dijiong Wu

  2. Department of Hematology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang, 310005, China

    Yingying Shen, Huijin Hu, Wenbin Liu, Yuechao Zhao, Yiping Shen, Yuhong Zhou, Baodong Ye & Dijiong Wu

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  1. Qi Liu
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  10. Baodong Ye
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Contributions

Dijiong Wu and Baodong Ye conceived and designed the study. Yuzhu Li, Huijin Hu, Wenbin Liu., Yuechao Zhao, and Huijie Dong assisted in the acquisition of data. Qi Liu, Yingying Shen, Dijiong Wu, Yiping Shen, and Baodong Ye analyzed and interpreted the data. Qi Liu and Dijiong Wu wrote, reviewed, and revised the manuscript. All authors contributed toward data analysis, drafting, and critically revising the paper and agree to be accountable for all aspects of the work.

Corresponding authors

Correspondence to Baodong Ye or Dijiong Wu.

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Ethics approval and consent to participate

This study was approved by the ethical committee of the First Affiliated Hospital of Zhejiang Chinese Medical University. 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.

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The authors declare no competing interests.

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Qi Liu and Yingying Shen have equal contribution

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Liu, Q., Shen, Y., Li, Y. et al. Efficiency and safety of eltrombopag for multi-line failed Chinese patients with immune thrombocytopenia: cases with decreased megakaryocyte response well from single-center experience. Immunol Res 70, 67–74 (2022). https://doi.org/10.1007/s12026-021-09245-w

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