Eltrombopag for patients with moderate aplastic anemia or uni-lineage cytopenias
| Autor: | Ruba Shalhoub, Neal S. Young, Fernanda Gutierrez-Rodrigues, Katherine R. Calvo, Ma Evette Barranta, Xing Fan, Ronan Desmond, Stephanie Sellers, Bogdan Dumitriu, Thomas Winkler, Colin O. Wu, Danielle M. Townsley, Janet Valdez, David J. Young, Maher Albitar, Jennifer Lotter, Cynthia E. Dunbar |
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| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_specialty
Hematopoiesis and Stem Cells Anemia Eltrombopag Phases of clinical research Benzoates Gastroenterology chemistry.chemical_compound hemic and lymphatic diseases Internal medicine medicine Humans Prospective Studies Aplastic anemia Diamond–Blackfan anemia Prospective cohort study Cytopenia business.industry Anemia Aplastic Hematology medicine.disease Hydrazines medicine.anatomical_structure chemistry Pyrazoles Bone marrow business |
| Zdroj: | Blood Advances. 4:1700-1710 |
| ISSN: | 2473-9537 2473-9529 |
| DOI: | 10.1182/bloodadvances.2020001657 |
| Popis: | There is no standard or widely effective treatment of patients with moderate aplastic anemia (MAA) or hypo-productive uni-lineage cytopenias (UC). Eltrombopag (EPAG), a small molecule thrombopoietin mimetic, has previously been shown to result in durable multi-lineage hematologic responses with low toxicity in patients with refractory severe aplastic anemia (SAA). Its safety and efficacy in MAA are unknown. This prospective phase 2 study enrolled previously untreated and treated MAA and UC patients with clinically relevant cytopenias. EPAG was administered at doses escalating from 50 to 300 mg/d. Hematologic responses were assessed at 16 to 20 weeks. Responding patients were continued on EPAG until reaching defined robust or stable blood counts. EPAG was reinstituted for relapse. Thirty-four patients were enrolled between 2012 and 2017, including 31 with MAA and 3 with UC. Seventeen patients responded in at least 1 eligible lineage by the primary end point. A striking improvement in anemia was observed in a patient with Diamond-Blackfan anemia. EPAG was well tolerated, and it was discontinued for robust or stable blood counts in 12 of 17 patients after a median of 8 months. A majority required re-initiation of EPAG for declining counts, and all regained response. Two of 34 patients developed non–chromosome 7 bone marrow cytogenetic abnormalities while taking EPAG, without dysplasia or increased blasts. Somatic mutation allele frequencies in cancer genes did not increase overall on EPAG. EPAG is a well-tolerated oral treatment of cytopenias in patients with MAA/UC. This trial was registered at www.clinicaltrials.gov as #NCT01328587. |
| Databáze: | OpenAIRE |
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