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

Yi Wang, Fengkui Zhang, Liansheng Zhang, Miao Miao, Xinjian Liu, Hong Liu, Yingmei Li, Zheng Ge, Rong Fu, Xiaoyan Ge, Wenrui Yang, Fei Li, Tong Chen, Shunqing Wang, Sujun Gao, Bing Han, Hong Chang, Guangsheng He, Xin Zhao

Journal: Annals of hematology 2022;101(12):2611-2616

PMID: 36220881

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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.

Address: 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.; Jiangsu Province Hospital, Nanjing, China.; Institute of Hematology, West China Hospital of Sichuan University, Chengdu, China.; Peking Union Medical College Hospital, Beijing, China.; The First Hospital of Bethune, Jilin University, Changchun, China.; Guangzhou First People's Hospital, Guangzhou, China.; Huashan Hospital Affiliated to Fudan University, Shanghai, China.; The First Affiliated Hospital of Nanchang University, Nanchang, China.; Shaanxi Provincial People's Hospital, Xi'an, China.; The Second Hospital of Shanxi Medical University, Taiyuan, China.; Tianjin Medical University General Hospital, Tianjin, China.; Zhongda Hospital Affiliated to Southeast University, Nanjing, China.; The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.; Affiliated Hospital of Nantong University, Nantong, China.; Henan Cancer Hospital, Zhengzhou, China.; The First Affiliated Hospital of Suzhou University, Suzhou, China.; Lanzhou University Second Hospital, Lanzhou, China.; 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. [email protected].

DOI: 10.1007/s00277-022-04968-8

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https://dx.doi.org/10.1007/s00277-022-04968-8

MeSH Terms: Humans, Anemia, Aplastic, Pyrazolones, Hydrazones, Thrombopoietin, Iron Chelating Agents