Avatrombopag Added to Standard Immunosuppressive Therapy for Severe Aplastic Anemia

Acquired aplastic anemia is immune-mediated bone marrow failure disease. Antithymocyte globulin (ATG) and cyclosporine based immunosuppressive therapy (IST) is effective for severe aplastic anemia (SAA), but only 12-17% of patients achieve complete response at 6 months. Complete hematologic response predicts better survival of patients, so clinicians have been trying to further improve the complete response rate. Addition of eltrombopag improves both the overall response rate and complete response rate of SAA patients, but its hepatotoxicity is still worrying. Avatrombopag is a novel, oral, small-molecule thrombopoietin receptor agonist being developed to provide a predictable increase in platelet counts in immune thrombocytopenia and thrombocytopenia in patients with chronic liver disease. To date, there is no report on the effectiveness of avatrombopag in treating aplastic anemia.

Here we enrolled 32 severe and very severe aplastic anemia (SAA/VSAA) patients who received ATG, cyclosporine and avatrombopag as first-line treatment between June 2021 and March 2022. Thirty-one patient received porcine ATG (20mg/kg.d for 5 consecutive days) and one patient received rabbit ATG (3mg/kg.d for 5 consecutive days). Avatrombopag was added within 3 months after ATG initiation at dose of 40-60mg per day and administered for at least 3 months. Cyclosporine was given orally at dose of 3.5-5mg/kg.d.

There were 17 SAA patients and 15 VSAA patients. The median neutrophil count was 0.31 (range 0.01-1.01) ×10⁹/L, median reticulocyte count was 8 (range 2-54) ×10⁹/L, and median platelet count was 5 (range 1-16) ×10⁹/L. All patients achieved the end-point of 3 months and 23 patients achieved end-point of 6 months. One patient with VSAA died at 1 month due to infections and was counted as no response at 3 months and 6 months. The rate of complete response was 15.6% and rate of overall response was 46.9% at 3 months. The rate of complete response at 6 months was 30.4% and rate of overall response was 65.2%. The complete response rate at 3 months and 6 months were both higher than historical results of standard IST (ATG and cyclosporine, 5.2% at 3 months and 14.6% at 6 months). Avatrombopag was safe, and there was no drug-related liver dysfunction. No patient discontinued avatrombopag due to adverse events.

In conclusion, the addition of avatrombopag to IST was safe and associated with higher complete response rate among patients with SAA/VSAA.

No relevant conflicts of interest to declare.