Long-term eltrombopag for bone marrow failure depletes iron.

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.

• Authors: David J Young, Xing Fan, Emma M Groarke, Bhavisha Patel, Ronan Desmond, Thomas Winkler, Andre Larochelle, Katherine R Calvo, Neal S Young, Cynthia E Dunbar
• Journal: American journal of hematology (Am J Hematol) Vol. 97 Issue 6 Pg. 791-801 (06 01 2022) ISSN: 1096-8652 [Electronic] United States
• PMID: 35312200 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)
• Copyright: Published 2022. This article is a U.S. Government work and is in the public domain in the USA.

Chemical References

• Benzoates
• Hydrazines
• Pyrazoles
• Ferritins
• Iron
• eltrombopag

Topics

• Anemia, Aplastic (drug therapy)
• Benzoates (adverse effects)
• Ferritins
• Humans
• Hydrazines
• Iron (therapeutic use)
• Iron Overload (chemically induced, etiology)
• Pancytopenia (chemically induced)
• Pyrazoles
• Recurrence
• Thrombocytopenia (chemically induced)