Long-term eltrombopag for bone marrow failure depletes iron.
Am J Hematol
; 97(6): 791-801, 2022 06 01.
Article
en En
| MEDLINE
| ID: mdl-35312200
ABSTRACT
Eltrombopag (EPAG) has been approved for the treatment of aplastic anemia and for immune thrombocytopenia, and a subset of patients require long-term therapy. Due to polyvalent cation chelation, prolonged therapy leads to previously underappreciated iron depletion. We conducted a retrospective review of patients treated at the NIH for aplastic anemia, myelodysplastic syndrome, and unilineage cytopenias, comparing those treated with EPAG to a historical cohort treated with immunosuppression without EPAG. We examined iron parameters, duration of therapy, response assessment, relapse rates, and common demographic parameters. We included 521 subjects treated with (n = 315) or without EPAG (n = 206) across 11 studies with multiyear follow-up (3.6 vs. 8.5 years, respectively). Duration of EPAG exposure correlated with ferritin reduction (p = 4 × 10-14 ) regardless of response, maximum dose, or degree of initial iron overload. Clearance followed first-order kinetics with faster clearance (half-life 15.3 months) compared with historical responders (47.5 months, p = 8 × 10-10 ). Risk of iron depletion was dependent upon baseline ferritin and duration of therapy. Baseline ferritin did not correlate with response of marrow failure to EPAG or to relapse risk, and timing of iron clearance did not correlate with disease response. In conclusion, EPAG efficiently chelates total body iron comparable to clinically available chelators. Prolonged use can deplete iron and ultimately lead to iron-deficiency anemia mimicking relapse, responsive to iron supplementation.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Pancitopenia
/
Trombocitopenia
/
Sobrecarga de Hierro
/
Anemia Aplásica
Tipo de estudio:
Etiology_studies
Límite:
Humans
Idioma:
En
Revista:
Am J Hematol
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos