Avatrombopag improves platelet engraftment after haploidentical hematopoietic stem cell transplantation: A randomized, double-blind, multicenter, placebo-controlled trial
Year: 2025
Type: conference-abstract
Abstract: Introduction: Delayed platelet (PLT) recovery is a common complication following haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Improved platelet recovery may reduce the need for transfusions and improve transplant outcomes. Thrombopoietin receptor agonists (TPO-RAs) have been used in various types of thrombocytopenic disorders, including prolonged thrombocytopenia after allo-HSCT. Our previous retrospective study revealed the safety and efficacy of avatrombopag, a TPO-RA, in the treatment of primary delayed platelet engraftment and secondary failure of platelet engraftment after haplo-HSCT. However, prospective evidence is limited. In this study, we performed a randomized, double-blind, multicenter, placebo-controlled trial to investigate the safety and efficacy of avatrombopag in enhancing platelet recovery after haplo-HSCT. This study is registered at ClinicalTrials.gov as NCT06202625. Methods: This prospective multicenter trial were performed in 10 centers in China and included patients 18–65 years old who underwent haplo-HSCT. Patients were excluded if they had active infection; liver or kidney injury (ALT or AST>3 ULN, or total Bil>2 ULN, or Ccr<50 mL/min); a history of arteriovenous thrombosis or cardiovascular disease; a history of drug use to promote platelet production two weeks before enrollment, including but not limited to TPO-RAs; or secondary or multiple HSCTs. Patients known to be allergic to avatrombopag and any of its excipients were also excluded. The enrolled patients received avatrombopag 20 mg/day or placebo on a 1:1 randomization schedule starting on Day 7. The primary objective was to assess the proportion of participants who achieved a PLT count of ≥50×10⁹/L and remained independent of PLT transfusion for ≥7 consecutive days by Day 60. Key secondary endpoints included: the proportions of participants with a PLT count of ≥50×10⁹/L and ≥20×10⁹/L on Day 30; and the proportion of participants with a PLT count of ≥100×10⁹/L on Day 60 who remained free from PLT transfusion for ≥7 consecutive days. Avatrombopag 20 mg/d or placebo was taken orally from +D7 after haplo-HSCT until reaching the adjustment indication or to Day 60 after haplo-HSCT. Results: From March 1st, 2024, to July 21st, 2025, 100 patients (50 in the avatrombopag group and 50 in the control group) were included. The median time to platelet recovery (>20×109/L) was 13 days for patients treated with avatrombopag and 14 days for controls (P= 0.087). Compared with patients in the control group, significantly more patients in the avatrombopag group achieved a PLT level ≥50×109/L without the need for PLT transfusion for ≥7 consecutive days by Day 30 (78.0% vs. 56.0%, P=0.019). On Day 60, 74.0% of patients in the avatrombopag group had a platelet count of ≥50×10⁹/L and did not require platelet transfusion for 7 or more consecutive days, whereas 60.0% of patients in the control group did (P=0.164). The proportion of participants whose PLT level ≥20×109/L or ≥100×109/L on Day 60, PLT≥50×109/L or PLT≥100×10^9/L on Day 90 after haplo-HSCT independent of PLT transfusion for ≥7 consecutive days were comparable between the avatrombopag group and the control group . No patients in either group experienced grade ≥3 adverse events. The number of platelet transfusions received, overall survival, progression-free survival, GVHD rate, relapse rate, and nonrelapse mortality were similar between the two groups. Conclusion: Overall, this represents the first randomized, double-blind, multicenter, placebo-controlled trial to confirm that avatrompag is effective and safe in improving platelet recovery after haplo-HSCT.
Source: Blood
Authors: Hai-Xia Fu, Yuanyuan Zhang, Xiao-Dong Mo, yuqian Sun, Chen-hua Yan, Feng-Rong Wang, Zhi-Dong Wang, Jun Kong, Yuqian Sun, Meng Lv, Yao Chen, Yuhong Chen, Ting-ting Han, Yu Wang, Lanping Xu, Shenjin Fan, Hongyu Zhang, Shun-Qing Wang, Yicheng Zhang, Yuanbin Wu, Linghui Xia, Yajing Xu, Fei Li, Erlie Jiang, Xiaojun Huang, Xiaohui Zhang
Institutions: Peking University, Peking University People's Hospital, Tongji Hospital, Huazhong University of Science and Technology, Harbin Medical University, First Affiliated Hospital of Harbin Medical University, Peking University Shenzhen Hospital, Guangzhou First People's Hospital, South China University of Technology, Guangzhou University of Chinese Medicine, Wuhan Union Hospital, Central South University, Xiangya Hospital Central South University, Nanchang University, First Affiliated Hospital of Jiangxi Medical College, First Affiliated Hospital of Nanchang University, Chinese Academy of Medical Sciences & Peking Union Medical College, Institute of Hematology & Blood Diseases Hospital
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4417013462
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