Comparative study of hetrombopag vs. eltrombopag in promoting platelet engraftment post-autologous hematopoietic stem cell transplantation: A multicenter clinical trial

Abstract

Abstract Background and Purpose：Autologous hematopoietic stem cell transplantation (auto-HSCT) is an important therapeutic approach for diseases such as lymphoma and myeloma. Similar to allogeneic transplantation, some patients also experience poor or delayed platelet engraftment after auto-HSCT. Thrombocytopenia can increase the risk of organ bleeding in patients and even affect the consolidation chemotherapy for this disease in the later stage. Thrombopoietin receptor agonists (TPO-RAs), used in the treatment of immune thrombocytopenia (ITP) and aplastic anemia (AA), are now being applied to manage post-transplant thrombocytopenia in both allogeneic and autologous HSCT. Hetrombopag and eltrombopag are two commonly used TPO-RAs in China, but comparative studies on their efficacy in promoting platelet engraftment following auto-HSCT have not been reported. Therefore, this study aims to compare the clinical efficacy and adverse events of these two TPO-RAs (hetrombopag and eltrombopag) in promoting platelet recovery after auto-HSCT. Methods：Data were collected from eleven transplant centers, including clinical cases where hetrombopag or eltrombopag was administered 3–7 days after autologous stem cell infusion to promote platelet reconstitution. The initial dose of hetrombopag was 2.5-5.0 mg/day, and that of eltrombopag was 25–50 mg/day, continued until platelet recovery. Results：A total of 51 patients were enrolled and analyzed. Among them, 17 cases received eltrombopag treatment (3 cases with an initial dose of 25mg/d and 14 cases with 50mg/d), 34 cases received eltrombopag treatment (5 cases with an initial dose of 2.5mg/d and 29 cases with 5.0mg/d). The cohort included 27 males and 24 females, with a median age of 54 years (range: 18-70). Diagnoses included multiple myeloma (MM, n=29), acute myeloid leukemia (AML, n=3), T-cell lymphoma (n=6), diffuse large B-cell lymphoma (n=8), mantle cell lymphoma (n=4), and Hodgkin's lymphoma (n=1). Pre-transplant response assessment showed complete remission (CR) in 43 patients and partial/very good partial remission (PR/VGPR) in 8. The median number of prior chemotherapy cycles was 6 (range: 2-20). The mean infused CD34+ cell count was 6.9×10⁶/kg, and the mean mononuclear cell (MNC) count was 9.0×10⁸/kg. Among these 51 patients, the average time of neutrophil engraftment was 11.3±2.3 days, with 10.7±2.3 days in the Hetrombopag group and 12.4±1.9 days in the eltrombopag group (p=0.018). However, when comparing only the higher-dose subgroups (hetrombopag 5mg/day, n=29; eltrombopag 50 mg/day, n=14), the difference was not statistically significant (11.0±2.2 vs. 12.1±2.0 days, p=0.094). Secondly, the average time of platelet engraftment in the total population was 14.4±4.8 days, among which it was 12.9±2.4 days for Hetrombopag group and 17.4±6.7 days for eltrombopag group (p=0.017). In the higher-dose subgroups, platelet recovery also remained significantly faster with hetrombopag treatment (13.2±2.4 vs. 17.6±7.3 days, p =0.042). From stem cell reinfusion to platelet engraftment, the average platelet transfusion in the eltrombopag group was 2.8±1.5 U, and that in the Hetrombopag group was 2.3±1.2 U (p=0.233). All adverse events were grade 1-2 and resolved with supportive care. Among 51 patients, fever occurred in 15 (hetrombopag: 9, 60%; eltrombopag: 6, 40%), headache in 3 (hetrombopag: 1, 33.3%; eltrombopag: 2, 66.7%), dizziness in 3 (all eltrombopag), diarrhea in 3 (hetrombopag: 2, 66.7%; eltrombopag: 1, 33.3%), fatigue in 1 (hetrombopag), rash in 2 (hetrombopag), elevated liver enzymes in 2 (hetrombopag), and renal dysfunction in 1 (hetrombopag). Conclusion：This study is the first to demonstrate that hetrombopag significantly accelerates neutrophil and platelet engraftment in auto-HSCT patients compared to eltrombopag.