Language

English

Publication Date

8-12-2025

Journal

Blood Advances

DOI

10.1182/bloodadvances.2024015102

PMID

40315366

PMCID

PMC12305589

PubMedCentral® Posted Date

5-6-2025

PubMedCentral® Full Text Version

Post-print

Abstract

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/refractory (R/R) or treatment-naïve SAA. The eltrombopag starting dose was 25 mg/d for patients aged 1 to < 6 years and 50 mg/d for patients aged 6 to < 18 years; dose modifications (maximum dose, 150 mg/d) were allowed to achieve a target platelet count of 50 × 109/L to 200 × 109/L. Eltrombopag was administered with cyclosporine A, with or without horse antithymocyte 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: R/R and treatment-naïve cohorts. The 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. The most common treatment-related adverse events were abnormalities in liver function tests, including increased bilirubin (43.1%), alanine aminotransferase (37.3%), and aspartate aminotransferase (33.3%). Eltrombopag with IST showed a trend toward a favorable ORR in the R/R cohort, with no new safety signals.

Keywords

Humans, Anemia, Aplastic, Pyrazoles, Hydrazines, Benzoates, Child, Female, Male, Child, Preschool, Adolescent, Immunosuppressive Agents, Infant, Treatment Outcome, Cyclosporine, Drug Therapy, Combination, Severity of Illness Index

Comments

This trial was registered at www.clinicaltrials.gov as #NCT03025698.

Published Open-Access

yes

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