Efficacy and Safety of Avatrombopag in Combination with Standard Immunosuppressive Therapy for Severe Aplastic Anemia

Background: Severe aplastic anemia (SAA) is a life-threatening bone marrow failure disease. The addition of eltrombopag to immunosuppressive therapy (IST) improves the response rate and response quality of SAAs, but its hepatotoxicity is concerning. Avatrombopag (AVA), another small-molecule thrombopoietin receptor agonist without hepatotoxicity, has unknown efficacy in SAA treatment. Methods: This retrospective study compared clinical outcomes of 42 SAA patients treated with IST and AVA as first-line treatment (Group A) to a historical cohort of 84 patients who received IST alone (Group B) using propensity score matching (PSM). Results: The median age was 31.5 (6.0-67.0) years old in Group A and 26 (16.0-45.0) years old in Group B. At 3 months, Group A showed higher complete response (CR) and overall response (OR) rates than Group B (CR: 19.0% vs. 4.8%, P = 0.024; OR: 54.8% vs. 39.3%, P =0.145). Higher CR and OR rates were also found at 6 months in Group A than in Group B (CR 31.0% vs. 14.3%, P =0.145; OR 71.4% vs. 51.2%, P =0.048). In multivariate analysis of Group A, a shorter interval from disease onset to ATG treatment (≤6 months) ( P =0.005) predicted better responses rate at 6 months. Event free survival was also improved in Group A (60.7% vs. 49.6%). AVA was well-tolerated, with no hepatic injury observed during treatment, even in those with pre-existing hepatic impairment. Conclusion: The addition of AVA to IST improves both the response rate and response quality in SAA patients while ensuring safety.