Efficacy and safety of different TPO-RAs combined with cyclosporine in the treatment of NSAA.

BACKGROUND: TPO receptor agonists (TPO-RAs) have significantly improved the treatment outcomes of patients with aplastic anemia. Currently, three small-molecule TPO-RAs (eltrombopag, hetrombopag, and avatrombopag) are available for clinical use and work well. OBJECTIVES: This article aims to compare the efficacy and safety of these TPO-RAs in treating non-severe aplastic anemia (NSAA). DESIGN: This was a single-center, retrospective observational cohort study. METHODS: A retrospective analysis was performed to assess the efficacy and side effects of cyclosporine A (CsA) combined with different TPO - RAs in 67 NSAA patients. Patients were divided into three groups according to the type of TPO-RA received: eltrombopag, hetrombopag, or avatrombopag. The overall response rate (ORR) was evaluated at 3 months and 6 months after treatment initiation. Adverse events, including liver impairment, infection, and death, were recorded and compared among the three groups. RESULTS: In total,the 3-month overall response rate (ORR) of CsA combined with TPO-RAs was 71.6%, the 6-month ORR was 82.1%. The ORRs among eltrombopag, hetrombopag, and avatrombopag groups were no statistically significant difference at the 3-month (P=0.334) or 6-month (P=0.776). Due to the pre-screening of patients with underlying liver conditions, the occurrence of side effects including new liver impairment, infection and death, showed no significant differences among the three groups. High level of absolute reticulocyte count at enrollment and adequate initial treatment dose of TPO-RAs are independent factors for better efficacy at 6 months. Old age (P=0.034) and infection(P=0.000) were the independent factors affecting the duration of hospitalization. CONCLUSIONS: This study shows that eltrombopag, hetrombopag, and avatrombopag combined with CsA have comparable efficacy in the treatment of NSAA. Identifying patients at high risk for liver injury before treatment and initiating avatrombopag therapy represents a viable clinical treatment option for NSAA patients with pre-existing liver injury. Similar to SAA, NSAA patients should also be initiated with an adequate dose of TPO-RAs therapy. Elderly patients and those with concurrent infections are at higher risk of mortality, prolonged hospitalizations, and require more clinical attention.