Association between ferritin, hemoglobin, and anemia response in jaktinib-treated patients with myelofibrosis: A post-hoc analysis of the ZGJAK006 study.

person Yi Zhang The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China info_outline Yi Zhang, Hu Zhou, Zhi-Jian Xiao, Minghui Duan, Sujun Gao, Guangsheng He, Hongmei Jing, Junmin Li, Liangming Ma, Huanling Zhu, Chunkang Chang, Xin Du, Mei Hong, Xin Li, Qingchi Liu, Wei Wang, Na Xu, Haiping Yang, Qingwei Zhao, Jie Jin

Authors person Yi Zhang The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China info_outline Yi Zhang, Hu Zhou, Zhi-Jian Xiao, Minghui Duan, Sujun Gao, Guangsheng He, Hongmei Jing, Junmin Li, Liangming Ma, Huanling Zhu, Chunkang Chang, Xin Du, Mei Hong, Xin Li, Qingchi Liu, Wei Wang, Na Xu, Haiping Yang, Qingwei Zhao, Jie Jin Organizations The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China, Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China, Chinese Academy of Medical Sciences & Peking Union Medical College, Peking Union Medical College Hospital, Beijing, China, The First Hospital of Jilin University, Changchun, China, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Provincial People’s Hospital, Key Laboratory of Hematology of Nanjing Medical University, Collaborative Innovation Center for Cancer Personalize, Nanjing, China, Peking University Third Hospital, Beijing, China, Ruijin Hospital, Shanghai Jiaotong University Medical School, Shanghai, China, Shanxi Bethune Hospital, The Third Hospital of Shanxi Medical University, Taiyuan, China, West China Hospital, Sichuan University, Chengdu, China, Department of Hematology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China, Guangdong Provincial People's Hospital, Guangzhou, China, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, The Third Xiangya Hospital, Central South University, Changsha, China, The First Hospital of Hebei Medical University, Shijiazhuang, China, The Affiliated Hospital of Qingdao University, Qingdao, China, Nanfang Hospital, Southern Medical University, Guangzhou, China, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China Abstract Disclosures Research Funding Suzhou Zelgen Biopharmaceuticals Co, Ltd. Background: Iron metabolism is disrupted in MF through the increased production of hepcidin, contributing to increased ferritin levels and iron-binding capacity, decreased serum iron levels and hemoglobin levels. Hepcidin production is upregulated by JAK/STAT pathway and BMP6/ACVR1/SMAD pathway. Jaktinib showed inhibition effects on JAK family and ACVR1 in preclinical studies. Anemia benefits with jaktinib treatment were observed in several clinical studies in MF pts. To explore the underlying mechanisms, we conducted a post-hoc analysis to investigate the change of ferritin levels during jaktinib treatment in MF pts with and without anemia response from a phase 2 study in pts who were intolerant to ruxolitinib (the ZGJAK006 study). Methods: Pts from the ZGJAK006 study were included if they were RBC transfusion dependent or with hemoglobin level ≤100 g/L at baseline. Transfusion dependence was assigned to pts with an average RBC transfusion of ≥2 U/month within 3 months prior to study drug administration. Pts without baseline ferritin results were excluded. Eligible pts were divided into 2 groups: anemia responders by week 24 and non-responders by week 24. Anemia response was defined as becoming RBC transfusion independent (defined by no transfusion in ≥12 consecutive weeks and hemoglobin ≥85 g/L) for transfusion-dependent pts or a ≥20 g/L increase in hemoglobin for non-transfusion-dependent pts with baseline hemoglobin ≤100 g/L. Results: A total of 39 pts were included in this post-hoc analysis, with 14 anemia responders and 25 non-responders. The baseline hemoglobin was similar in responders (median: 78.5 g/L) and non-responders (median: 78.0 g/L). The baseline levels of ferritin were higher than upper limit of normal in most pts (69.2%) with a median of 784.6 ng/mL in the overall population (697.5 ng/mL in responders and 785.0 ng/mL in non-responders). Ferritin decreased to 583.9 and 531.7 ng/mL at weeks 12 and 24, respectively. Notably, anemia responders had a fast reduction in ferritin and increase in hemoglobin compared to non-responders. In addition, the hemoglobin levels of those non-responders maintained were stable and eight non-responders had a ≥50% decrease in RBC infusion frequency or unit. Six (42.9%) of 14 responders and 10 (40.0%) of 25 non-responders achieved spleen volume reduction of ≥ 35% from baseline at week 24. Conclusions: In this post-hoc analysis of pts with anemic MF, jaktinib treatment led to improvement in iron metabolism and anemia. The results were in consistence with the known activities of jaktinib against JAK family and ACVR1. Moreover, similar spleen responses were observed for anemia responders and non-responders. Nevertheless, ferritin was the only marker of iron metabolism measured in this study, a translational biology study evaluating hepcidin may be needed to further support the clinical findings. Clinical trial information: NCT04217993.

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