Pb2048: hematologic recovery induced by avatrombopag in saa refractory or intolerant to immunosuppressive therapy combined with eltrombopag

Topic: 12. Bone marrow failure syndromes incl. PNH - Clinical Background: Intensive immunosuppressive therapy (IST) combined with eltrombopag contributes to improving hematopoiesis in patients with severe aplastic anemia (SAA). Eltrombopag, however, is associated with elevations in alanine aminotransferase and bilirubin. As a small molecule TPO receptor agonist, avatrombopag can be administered orally with food with no significant hepatotoxicity. Aims: We evaluated efficacy and safety of avatrombopag in patients with SAA refractory or intolerant to IST combined with eltrombopag. Methods: 20 SAA patients switched from eltrombopag to avatrombopag at a dose of 40 mg/day in Jiangsu Province Hospital and Second Hospital of Nanjing from October 2020 to February 2023. The hematologic response and safety were analyzed in this study. The data was collected by prospective registration in the Chinese Eastern Collaboration Group of Anemia (ChiCTR2100045895). Results: The median age was 20(3–74) years old. A total of four patients who did not respond to IST combined with eltrombopag within a median time of 13(4–16) months. 15 cases (75%) obtained at least one lineage hematologic response [2 cases (10%) of complete response (CR) and 13cases (65%) of partial response (PR)]. The median time to first response was 42(14–207) days. 13 (65%) patients had a platelet response, with a median increase in platelet count of 21×109/L (range: 11–109). 10 patients who had platelet transfusions requirement became transfusion-independent within a median avatrombopag duration of 35(11–80) days. 9 patients (45%) had erythroid responses, with a median increase in hemoglobin level of 18g/L (range: 12–47). 7 patients had been dependent on packed red cell transfusions, and 6 of them (86%) no longer required transfusions at a median time of 41(14–72) days after avatrombopag. A total of 12 patients (60%) had a neutrophil response, with a median increase of 1.2×109/L (range: 0.3–2.1). No avatrombopag-related grade 2 or more adverse events occurred during the administration, and no thrombotic events occurred. Summary/Conclusion: Our research indicated avatrombopag had certain efficacy and good tolerance in patients with SAA refractory or intolerant to IST combined with eltrombopag, which deserved further exploration.Keywords: Severe aplastic anemia, Immunosuppressive therapy