Avatrombopag, a promising novel thrombopoietin receptor agonist for refractory/relapsed/intolerant non-severe aplastic anemia: a phase 2 single-arm clinical trial

The therapeutic options for thrombocytopenia in non-severe aplastic anaemia (NSAA) are limited. Avatrombopag (AVA) is prescribed for thrombocytopenic diseases but not for NSAA. Herein, we conducted a phase 2, non-randomized, single-arm trial to explore the efficacy and safety of AVA in refractory/relapsed/intolerant NSAA. AVA dose was initiated at 20 mg/d and titrated to a maximum of 60 mg/d. The primary endpoint was the haematological response at 3 months. Twenty-five patients were analyzed. The overall response rate (ORR) at 3 months was 56% (14/25), with 12% (3/25) achieving a complete response (CR). At a median follow-up of 7 (3–10) months, the OR and CR rates were 52% and 20%, respectively. Responders had a shorter duration of diagnosis of AVA administration than non-responders (10 (6–80) <i>vs</i> 37 (6–480) months, <i>p</i> = 0.027) and belonged to the relapsed/intolerant NSAA type (71% <i>vs</i> 27%, <i>p</i> = 0.047); 44% (8/18) patients previously treated with eltrombopag before enrollment responded at 3 months, with an average prior eltrombopag dose of median 72.5 (50–100) mg/d and an average AVA dose for a response of median 43.5 (20–60) mg/d. 3-month ORR had no significant correlation with eltrombopag exposure (<i>p</i> = 0.09), prior eltrombopag length (<i>R</i>²=0.11), or cumulative eltrombopag dose (<i>R</i>²=0.30). Only one patient relapsed after stopping AVA for 1 month. No serious AVA-related side effects or clone evolution were detected. AVA is effective and well-tolerated in NSAA patients who are refractory, relapsed, or intolerant to CsA/tacrolimus ± eltrombopag. Earlier treatment and relapsed/intolerant AA may show a better short-term response rate. More studies are needed to define the optimal dose and the long-term efficacy (NCT04728789).