Efficacy and Safety of Hetrombopag in the Treatment of Chemotherapy-Induced Thrombocytopenia in Pediatric Acute Leukemia
Authors: Yang Chunhui , Yin Runxiu , Li Lijuan , Song Chunyan , Li Huiyuan , Xiao Zugang , Duan Shaoqin , Tian Xin 
Published: December 2024

Background
Chemotherapy remains the primary treatment modality for pediatric acute leukemia. However, a notable side effect is the suppression of megakaryocytes in the bone marrow, leading to chemotherapy-induced thrombocytopenia (CIT). Hetrombopag, a thrombopoietin receptor agonist (TPO-RA), was approved in China for chronic immune thrombocytopenia in adults and for severe aplastic anemia refractory to immunosuppressive therapy. This study aimed to assess the efficacy and safety of hetrombopag in treating CIT in pediatric patients with acute leukemia.
Methods
The study included 160 pediatric patients, aged 3 to 16 years, diagnosed with acute leukemia. Among them, 80 patients with platelet counts (PLT) below 100 × 109/L post-chemotherapy received oral hetrombopag (daily dose: 2.5 mg for weight ≤ 25 kg, 5 mg for weight 25-45 kg, 7.5 mg for weight ≥ 45 kg), forming the treatment group. The remaining 80 patients, who did not receive thrombopoietic drugs post-chemotherapy, comprised the control group. Outcomes included response rate (defined as PLT ≥100 × 109/L or an increase of ≥30 × 109/L within one week), platelet counts at one week and two weeks post-treatment, proportion of patients whose platelet counts returned to 50× 109/L and 100× 109/L within two weeks, time to reach PLT ≥75 × 109/L, time to achieve platelet counts of 100 × 109/L, number of platelet transfusions, length of hospital stay and safety.
Results
The median ages of the treatment and control groups were 7.3 years (range 3-14) and 7.3 years (range 3-16), respectively, with males constituting 57.5% and 51.3% of each group. In the treatment group, patients with acute myeloid leukemia, T-cell acute lymphoblastic leukemia, and B-cell acute lymphoblastic leukemia accounted for 25.0%, 20.0%, and 55.0% versus 25.0%, 31.3%, and 43.8% in the control group. Additionally, 77.5% and 22.5% of patients were in the consolidation and induction chemotherapy phases, respectively, in both the treatment and control groups. The treatment group exhibited a response rate of 50.0% (95% CI, 38.6-61.4) compared to 28.8% (95% CI, 19.2-40.0) in the control group (P = 0.0059). Median PLT values at one week and two weeks were 34.0 (range 14.0-80.0) × 109/L and 98.5 (range 17.0-189.0) × 109/L in the treatment group, versus 25.0 (range 3.0-80.0) × 109/L (P &lt; 0.0001) and 72.0 (range 10.0-320.0) × 109/L (P=0.005) in the control group. The proportion of patients whose platelet count returned to 50× 109/L within two weeks was 95% (95% CI, 87.7-98.6) in the treatment group and 73.8% (95% CI, 62.7-83.0) in the control group (P=0.0002), and the corresponding proportions for a return to 100× 109/L were 48.8% (95% CI, 37.4-60.2) and 30% (95% CI, 20.3-41.3, P=0.0152). The median time to reach PLT ≥75 × 109/L was 12 days (range 7-26) for the treatment group and 15 days (range 7-55) for the control group(P=0.001). The median time to normal platelet count (100 × 109/L) was 14 days (range 8-21) in the treatment group and 16.5 days (range 10-65) in the control group (P &lt; 0.0001). The treatment group had a median hospital stay of 20.5 days (range 14.0-27.0), compared to 24.0 days (range 16.0-60.0) for the control group. Additionally, the median number of platelet transfusions was 1.0 (range 0.0-5.0) in the treatment group, versus 2.0 (range 1.0-9.0) in the control group. All these differences were statistically significant (P &lt; 0.001). All-grade treatment-emergent adverse events occurred in 47.5% of patients in the treatment group versus 57.0% in the control group, with one patient (1.3%) experiencing grade 3 aspartate aminotransferase increased in each group.
Conclusion
This study provided the first evidence that hetrombopag was efficacy for the treatment of pediatric acute leukemia CIT patients with a good safety profile. Hetrombopag can significantly improve platelet counts within a short period, reduce hospital stay duration, minimize bleeding risks, and decrease the need for emergency treatments. Further validation with large sample size and prospective clinical studies are needed.