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Iron chelation of hetrombopag in aplastic anemia: a post hoc analysis of a phase II study

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Abstract

Hetrombopag is the only CFDA-approved thrombopoietin (TPO) receptor agonist for severe aplastic anemia (SAA) in China. Its chemical structure has an iron chelation domain. To explore the iron chelation effect of hetrombopag, we performed a post hoc analysis of the phase II clinical trial (NCT03557099). Thirty-five immunosuppressive therapy (IST)–refractory SAA patients were enrolled in the study, and the longitudinal changes of serum ferritin (SF) were assessed. At 18 weeks post-hetrombopag initiation, 51.4% of patients showed decreased SF levels by a median of 49.0 (18.1–95.5) % from baseline (median ΔSF decrease value, 917.2 ng/ml, range from 104.0 to 7030.0 ng/ml). A decrease in SF was found in 75.0% of hematologic responders and 31.6% of non-responders. Among the 24 patients with iron overload, 12 had decreased SF levels by up to 51% of the baseline. Patients with normal SF levels also showed decreased SF levels, and iron deficiency occurred in two patients. In conclusion, hetrombopag showed a powerful and rapid iron chelation effect.

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Acknowledgements

The authors would like to thank the patients and families who participated in this clinical trial. Support for this trial was provided by Jiangsu Hengrui Pharmaceuticals Co., Ltd, the manufacturers of hetrombopag, who also supplied the study drug.

Funding

This study was supported by Grant 81900127 of the National Nature Science Foundation of China by Grant 2020-RW310-002 of the Non-profit Central Research Institute Fund of Chinese Academy of Medical Science.

Author information

Author notes

  1. Wenrui Yang and Xin Zhao contributed equally.

Authors and Affiliations

  1. State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Chinese Academy of Medical Sciences & Peking Union Medical College, 288 Nanjing Road, Heping District, Tianjin, 300020, China

    Wenrui Yang, Xin Zhao & Fengkui Zhang

  2. Jiangsu Province Hospital, Nanjing, China

    Guangsheng He

  3. Institute of Hematology, West China Hospital of Sichuan University, Chengdu, China

    Hong Chang

  4. Peking Union Medical College Hospital, Beijing, China

    Bing Han

  5. The First Hospital of Bethune, Jilin University, Changchun, China

    Sujun Gao

  6. Guangzhou First People’s Hospital, Guangzhou, China

    Shunqing Wang

  7. Huashan Hospital Affiliated to Fudan University, Shanghai, China

    Tong Chen

  8. The First Affiliated Hospital of Nanchang University, Nanchang, China

    Fei Li

  9. Shaanxi Provincial People’s Hospital, Xi’an, China

    Yi Wang

  10. The Second Hospital of Shanxi Medical University, Taiyuan, China

    Xiaoyan Ge

  11. Tianjin Medical University General Hospital, Tianjin, China

    Rong Fu

  12. Zhongda Hospital Affiliated to Southeast University, Nanjing, China

    Zheng Ge

  13. The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

    Yingmei Li

  14. Affiliated Hospital of Nantong University, Nantong, China

    Hong Liu

  15. Henan Cancer Hospital, Zhengzhou, China

    Xinjian Liu

  16. The First Affiliated Hospital of Suzhou University, Suzhou, China

    Miao Miao

  17. Lanzhou University Second Hospital, Lanzhou, China

    Liansheng Zhang

Authors
  1. Wenrui Yang
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  2. Xin Zhao
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  4. Hong Chang
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  5. Bing Han
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  6. Sujun Gao
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  7. Shunqing Wang
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  8. Tong Chen
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  11. Xiaoyan Ge
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  12. Rong Fu
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  14. Yingmei Li
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  15. Hong Liu
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  16. Xinjian Liu
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  17. Miao Miao
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  18. Liansheng Zhang
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  19. Fengkui Zhang
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Contributions

Wenrui Yang performed research, analyzed the results, provided clinical care, and wrote the paper; Xin Zhao analyzed results and edited the paper; Guansheng He, Hong Chang, Bing Han, Sujun Gao, Shunqing Wang, Tong Chen, Fei Li, Yi Wang, Xiaoyan Ge, Rong Fu, Zheng Ge, Yingmei Li, Hong Liu, Xinjian Liu, Miao Miao, Liansheng Zhang performed research, and provided clinical care. Fengkui Zhang designed and performed research, analyzed the results, and edited the paper.

Corresponding author

Correspondence to Fengkui Zhang.

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This study was approved by the ethics committee of Blood Diseases Hospital, CAMS, and PUMC. All procedures followed were in accordance with the Helsinki Declaration of 1975, as revised in 2008. Patients provided written informed consent for data exploitation.

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Yang, W., Zhao, X., He, G. et al. Iron chelation of hetrombopag in aplastic anemia: a post hoc analysis of a phase II study. Ann Hematol 101, 2611–2616 (2022). https://doi.org/10.1007/s00277-022-04968-8

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