Avatrombopag improves platelet engraftment after haploidentical hematopoietic stem cell transplantation: A randomized, double-blind, multicenter, placebo-controlled trial

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.