Long-term eltrombopag for bone marrow failure depletes iron.
Long-term eltrombopag for bone marrow failure depletes iron.
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DOI：
10.1002/ajh.26543
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发表时间：
2022-06-01
影响因子：
12.8
通讯作者：
中科院分区：
文献类型：
--
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Eltrombopag （EPAG）已被批准用于治疗再生障碍性贫血和免疫性血小板减少症，部分患者需要长期治疗。由于多价阳离子螯合，长期治疗导致先前未被充分认识的铁耗尽。我们对在NIH治疗再生障碍性贫血、骨髓增生异常综合征和单株性细胞减少症的患者进行了回顾性研究，将接受EPAG治疗的患者与未接受EPAG免疫抑制治疗的历史队列进行了比较。我们检查了铁参数、治疗持续时间、反应评估、复发率和常见的人口统计学参数。我们在11项研究中纳入了521名接受EPAG治疗（n = 315）或未接受EPAG治疗（n = 206）的受试者，并进行了多年随访（分别为3.6年和8.5年）。EPAG暴露时间与铁蛋白减少相关（P = 4 × 10−14），与反应、最大剂量或初始铁过载程度无关。清除遵循一级动力学，与历史应答者（47.5个月，P = 8 × 10−10）相比，清除更快（半衰期15.3个月）。铁耗尽的风险取决于基线铁蛋白和治疗时间。基线铁蛋白与骨髓衰竭对EPAG的反应或复发风险无关，铁清除的时间与疾病反应无关。总之，EPAG与临床可用的螯合剂相比，可以有效地螯合全身铁。长期使用会耗尽铁，最终导致缺铁性贫血复发，对补铁有反应。
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 x 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 x 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.
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