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

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

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Publication Details

Journal
Blood Advances
Published
2025-05-02
DOI
https://doi.org/10.1182/bloodadvances.2024015102
Citations
4
Primary Topic
Hematopoietic Stem Cell Transplantation
Type
article
Field-Weighted Citation Impact
7.08

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article

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

Rukhmi Bhat, Bunchoo Pongtanakul, Kathleen Overholt, Alexey Maschan et al.
4 citations
Blood Advances
Hematopoietic Stem Cell Transplantation
7.08
article

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

Rukhmi Bhat, Bunchoo Pongtanakul, Kathleen Overholt, Alexey Maschan, Patrick Urban, Adrianna Vlachos, Jennifer Rothman, Nongnuch Sirachainan, Brigitte Strahm, Akiko Shimamura, Kelly Walkovich, Anabela Ferrão, Rabi Hanna, Sujith Samarasinghe, Jason E. Farrar, David A. Williams, Alison A. Bertuch, Taizo A. Nakano, Winfred C. Wang, Qinxia Wang, Liudmila Zubarovskaya, Carolyn M. Bennett, Patcharee Komvilaisak, Jessica Boklan, Chi Kong Li, Tze Fang Wong
article en
4 citations

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

Blood AdvancesVol. 9(15)
Northwestern University (US), Novartis (Switzerland) (CH), Boston Children's Hospital (US), Lurie Children's Hospital (US), Arkansas Children's Hospital (US), St. Jude Children's Research Hospital (US), Cleveland Clinic (US), Siriraj Hospital (TH), Harvard University (US), University of Arizona (US), Emory University (US), University of Freiburg (DE), Chinese University of Hong Kong (HK), Khon Kaen University (TH), Baylor College of Medicine (US), Mahidol University (TH), University of Michigan (US), First Pavlov State Medical University of St. Petersburg (RU), Great Ormond Street Hospital (GB), Great Ormond Street Hospital for Children NHS Foundation Trust (GB), University Medical Center Freiburg (DE), Riley Hospital for Children (US), Children's Hospital Colorado (US), Center for Cancer and Blood Disorders (US), Centro Hospitalar Lisboa Norte (PT), Prince of Wales Hospital (CN), Cohen Children's Medical Center (US), Novartis (United States) (US), Lurie Children's Hospital (US), Duke Medical Center (US), Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology (RU), Ramathibodi Hospital (TH), Children's Healthcare of Atlanta (US), Texas Children's Hospital (US), C. S. Mott Children's Hospital (US), Dana-Farber/Boston Children's Cancer and Blood Disorders Center (US), Robert H. Lurie Comprehensive Cancer Center of Northwestern University, University College London (GB), Indiana University – Purdue University Indianapolis (US), University of Arkansas for Medical Sciences (US), University of Colorado Denver (US)
American Society of Hematology, Pfizer, Novartis Pharma
Good health and well-being
Openalex Percentile: Top 3%
Hematopoietic Stem Cell Transplantation
7.08
DOIOpen Access PDFOpenAlex
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