Herombopag for Preventing Chemotherapy-Induced Thrombocytopenia in Lymphoma: A Single Center, Randomized Controlled, Phase II Study

Background: Chemotherapy-induced thrombocytopenia (CIT) is a prevalent complication associated with lymphoma treatment. It has the potential to cause delays in chemotherapy administration and result in suboptimal dosages, thereby elevating the risk of life-threatening bleeding incidents. Consequently, this condition can significantly impair the patient's prognosis. Here we explored the efficacy and safety of herombopag (a thrombopoietin receptor agonist, TPO-RA) in the management of CIT in patients with lymphoma. Methods:In this prospective, single center, randomized, blank-controlled, phase 2 trial，lymphoma patients who had previously encountered CIT following their most recent chemotherapy treatment were randomly assigned to the experimental group and the control group in a 1:1 ratio. Participants in the experimental arm were administered hetrombopag orally (initiating at a dosage of 2.5 or 5mg daily) commencing precisely 24 hours post-chemotherapy completion, as a prophylactic strategy against CIT, whereas no prophylaxis for CIT was given to the control group. Platelet counts were meticulously monitored every three days, and treatment-emergent adverse events (TEAEs) were documented throughout the study. The primary endpoint was the duration and severity of CIT. Secondary endpoints include the units of platelet transfusions, and safety. Results :From July 2022 to June 2024, 58 patients were enrolled, with 29 patients in each the experimental and control groups . The median age of the experimental and control groups were 54 years (range18-80) and 54 years (range 12-83), respectively, with males constituting 65.5% and 62.1% of each group. Baseline median platelet count was 167 (range 98-378)×109/L and 165 (range 91-460)×109/L in the experimental and control groups, respectively. Lymphoma staging, lines of treatment, bone marrow infiltration, platelet transfusion, and grading of the severity of previous CIT were comparable between the two groups. The nadir value of platelet and duration of the previous CIT were (42.79±22.51)×109 /L and 12.33±7.61 days in the experimental group, the corresponding value in the control group were (32.24±25.82)×109 /L and 12.36±7.15 days. Following hetrombopag prophylaxis, only 6.9% (2/28) of patients in the experimental group experienced grade 2 or higher CIT subsequent to this cycle of chemotherapy, a stark contrast to the control group (p＜0.001), where the incidence soared to 51.7% (15/28). The duration of CIT after this cycle of chemotherapy for both groups were 2.82±3.74 days and 12.21±6.75 days (p＜0.001).The experimental group exhibited a nadir platelet value of (104.31±47.2)×109 /L compared to (66.62±63.52)×109 /L in the control group (p＝0.013). Delayed chemotherapy were observed in 4 patients (13.8%) from the experimental group and 22 (78.6%) from the control group (p＜0.001). The incidence of dose reduction in the next cycle of antitumor therapy dose reduction were 3.4% (1/28) in the experimental group, versus 17.2% (5/28) in the control group (p＝0.105). There was no significant difference in the median amount of platelet transfusion between the two groups [1.5(range 1-2) VS. 3(range 1-3), p＝0.179]. All-grade TEAEs were occurred in 20.1% (6/28) of patients in the experimental group versus 17.2% (5/28) in the control group, all were transient and mild. Conclusions: Hetrombopag is an effective and well-tolerated alternative for secondary prevention of CIT in lymphoma, which has demonstrated the capacity to significantly mitigate the severity of CIT, shorten its duration, elevate the nadir platelet value and decrease the incidence of chemotherapy delays.