Eltrombopag in combination with immunosuppressive therapy in pediatric severe aplastic anemia: Phase 2 ESCALATE trial

• Eltrombopag combined with IST demonstrated a trend towards a favorable ORR in pediatric patients with r/r SAA.

• The PK profile for eltrombopag was similar to that observed in patients with ITP, and no unexpected safety signals were observed in children

Severe aplastic anemia (SAA) is a rare, life-threatening disease with acquired pancytopenia and hypocellular bone marrow. ESCALATE evaluated eltrombopag in combination with immunosuppressive therapy (IST) in pediatric patients (aged 1 to <18 years) with relapsed or refractory (r/r) or treatment-naïve SAA. The eltrombopag starting dose was 25 mg/day for patients aged 1 to <6 years and 50 mg/day for patients aged 6 to <18 years; dose modifications (maximum dose: 150 mg/day) were allowed to achieve a target platelet count of 50-200 × 109/L. Eltrombopag was administered with cyclosporine A, with or without horse anti-thymocyte globulin, for 26 weeks and could be extended if clinically beneficial. Fifty-one patients were treated (r/r SAA n=14; treatment-naïve SAA n=37). Data were analyzed overall and as 2 cohorts: the r/r cohort and the treatment-naïve cohort. Overall response rate (ORR; per North American Pediatric Aplastic Anemia Consortium criteria) at 26 weeks was 54.9% in both cohorts combined and 71.4% and 48.6% in the r/r and treatment-naïve cohorts, respectively; most responders had sustained responses after discontinuing eltrombopag. Among baseline transfusion-dependent patients, 66.7% and 76.7% achieved red blood cell and platelet transfusion independence, respectively with rates of 70% and 80% for the r/r cohort and 65.6% and 75.8% for the treatment-naïve cohort, respectively. Most common treatment-related adverse events were abnormalities of liver function tests, including increased bilirubin (43.1%), increased alanine aminotransferase (37.3%), and increased aspartate aminotransferase (33.3%). Eltrombopag with IST showed a trend towards a favorable ORR in the r/r cohort, with no new safety signals. www.ClinicalTrials.gov #NCT03025698