Evaluation of the Real-World Efficacy of Hetrombopag for the Treatment of Thrombocytopenia Post Allogeneic Hematopoietic Stem Cell Transplantation
Authors: MA Rui , Luo Xueyi , Sun Wei , Han Wei , He Yun , Wang Yu , Zhang Xiaohui , Xu Lanping , Liu Kaiyan , Huang Xiao Jun , Sun Yuqian 
Published: December 2024

Introduction
Thrombocytopenia following allogeneic hematopoietic stem cell transplantation (allo-HSCT) is associated with poorer transplant outcomes. Hetrombopag, a novel nonpeptide orally bioavailable thrombopoietin receptor agonist (TPO-RA), has shown durable platelet count response, reduced bleeding risk, and long-term safety in the treatment of immune thrombocytopenia. However, its use in real-world populations, characterized by their complexity and diversity, require further elucidation. This retrospective observational study aimed to evaluate the efficacy of hetrombopag for thrombocytopenia after allo-HSCT in real-world setting.
Methods
From June 2022 to April 2024, patients with persistent thrombocytopenia (including delayed platelet engraftment (DPE) and secondary failure of platelet recovery (SFPR)) following allo-HSCT who received hetrombopag therapy were included. All patients were given hetrombopag orally at an initial dose of 5 mg once daily, with an escalation to 7.5 mg once daily if no response was observed after one week. Response to treatment was defined as a platelet count of ≥20×109/L for at least 7 consecutive days without platelet transfusion support. The primary outcome was the proportion of responders. The platelet and megakaryocyte count before and after treatment were also evaluated.
Results
Among the 33 patients, 7 (21.2%) had DPE, and 26 (78.8%) had SFPR. The median age was 45 years (range: 22-60), with 19 (57.6%) males. Twenty-nine patients (87.9%) underwent haploidentical donor transplantation. The median time from allo-HSCT to platelet engraftment was 29 days (range: 10-188). The median platelet and megakaryocyte count before hetrombopag therapy was 14×109/L (range: 7-19) and 15.5 (range: 1-91), respectively. Hetrombopag treatment was initiated at a median of 56 days (range: 27-238) following allo-HSCT, with a median dose of 5 mg/day (range: 5-7.5). The median duration of treatment was 82 days (range: 26-214). Before hetrombopag treatment, 14 patients developed acute graft-versus-host disease (aGVHD), in which 5 patients had infections (including 3 cases of cytomegalovirus (CMV) infection, 1 case of Epstein-barr virus (EBV) infection, and 1 case of CMV and EBV infection, respectively). The overall platelet response rate was 81.8% (27/33), with 100% (7/7) in patients with DPE and 76.9% (20/26) in patients with SFPR. Among the 27 responsers, the median platelet and megakaryocyte count increased to 80×109/L (range: 28-212) and 58 (range: 5-118) after treatment. In patients with aGVHD prior to treatment, the platelet response rate was 85.7% (12/14). Besides, the platelet response was achieved in 80% (4/5) patients with both aGVHD and viral infections (CMV and/or EBV).
Conclusions
Our study suggests that hetrombopag is effective in elevating platelet level for the treatment of thrombocytopenia after allo-HSCT in the real world.