Efficacy of Combined Herombopag and Recombinant Human Thrombopoietin Therapy Compared to Monotherapy on Platelet Engraftment after Autologous Hematopoietic Stem Cell Transplantation in Patients
Authors: Wu Jing , Li Jieping , Wang Chaoyu , Huang Dehong , Guo Bingling , Liu Yao 
Published: December 2024

BackgroundAutologous hematopoietic stem cell transplantation (ASCT) is a promising approach for lymphoma. Post-transplant thrombocytopenia may lead to higher bleeding risk and worse prognosis. Therefore, exploring appropriate management to improve platelet engraftment is very important. Herombopag is an oral, non-peptide thrombopoietin receptor agonist (TPO-RA). Previous studies have demonstrated that herombopag monotherapy can effectively treat thrombocytopenia following ASCT, with a favorable safety profile. Recombinant human thrombopoietin (rhTPO) has a similar platelet-raising effect as endogenous thrombopoietin. Researches have shown that herombopag plus rhTPO can significantly enhance the intensity of the downstream MPL signaling pathway, suggesting a potential additive effect in promoting platelet production. Hence, this study aims to investigate whether the combination of herombopag and rhTPO can further enhance platelet engraftment following ASCT.

Methods This prospective study enrolled patients aged 18 years and older who had hematological diseases and were scheduled to undergo ASCT. Patients were randomly assigned to the herombopag plus rhTPO group (H + rhTPO group), the herombopag monotherapy group (H group), or the rhTPO monotherapy group (rhTPO group). All patients began treatment when their platelet counts were ≤ 50 × 109/L after autologous stem cell infusion. In the H group, herombopag was administered orally once daily, with the dosage based on baseline platelet levels. In the rhTPO group, rhTPO was administered as an injection once daily at a dose of 15,000 U. The H + rhTPO group received a combination of the two treatments. The primary endpoint was the time to platelet engraftment. The secondary endpoints included the time to white blood cell engraftment, the proportion of patients with platelet counts ≥ 50 × 109/L one month post-transplant, platelet counts at one month post-transplant, and safety.

Results Between January 2022 and January 2024, a total of 98 patients were enrolled. Among them, 45 were in the H + rhTPO group, 26 in the rhTPO group, and 27 in the H group. The median age of all patients was 53 years (range 26-71), with 61 male (62.2%). There were 81 patients with lymphoma (82.7%), 93 patients (94.9%) had a Karnofsky Performance Status (KPS) score of ≥ 70, and 41 patients (41.8%) had bone marrow involvement. The median platelet counts before treatment for the H + rhTPO, rhTPO, and H groups were 42 × 109/L, 27 × 109/L, and 35 × 109/L, respectively. The median dose of herombopag was 5 mg/day (range 2.5-7.5 mg/day) in both the H + rhTPO and H groups, with median durations of 12 days (range 2-27 days) and 13 days (range 4-22 days), respectively. The median duration of rhTPO administration was 11 days (range 1-18 days) in the H + rhTPO group and 9.5 days (range 2-16 days) in the rhTPO group.

Three months after ASCT, all patients in the monotherapy groups achieved leukocyte and platelet engraftment, while one patient in the combination group did not achieve platelet engraftment. The median time to platelet engraftment was 12 days in the H + rhTPO group, 13 days in the H group, and 14 days in the rhTPO group. The median time to leukocyte engraftment was 10 days in the H + rhTPO group and 11 days in both the H and rhTPO groups. One month post-transplantation, the proportion of patients with platelet counts ≥ 50×109/L was 93.0% (40/43) in the H + rhTPO group, 92.3% (24/26) in the H group, and 95.2% (20/21) in the rhTPO group. The median platelet counts one month post-transplantation were 151 (4-398) × 109/L, 150 (16-284) × 109/L, and 148 (33-277) × 109/L for the H+rhTPO, H, and rhTPO groups, respectively. Three months post-transplantation, the median platelet counts were 125 (15-346) × 109/L, 135 (28-247) × 109/L, and 144 (34-229) × 109/L, respectively. No statistically significant differences were observed in these efficacy indicators between the groups (P &gt; 0.05). No grade ≥ 3 adverse events were observed in any of the groups.

Conclusion For patients undergoing ASCT, herombopag monotherapy effectively promotes platelet engraftment. Adding rhTPO does not significantly enhance efficacy compared to herombopag alone. There are no statistically significant differences in engraftment rates, time to engraftment, or post-transplant platelet counts among the groups.