Eltrombopag for patients with moderate aplastic anemia or uni-lineage cytopenias
Eltrombopag for patients with moderate aplastic anemia or uni-lineage cytopenias
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DOI：
10.1182/bloodadvances.2020001657
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发表时间：
2020-04-28
期刊：
影响因子：
7.5
通讯作者：
Dunbar, Cynthia E.
中科院分区：
文献类型：
--
作者：
Fan, Xing;Desmond, Ronan;Dunbar, Cynthia E.
中度再生障碍性贫血（MAA）或低生产性单系细胞减少症（UC）患者尚无标准或广泛有效的治疗方法。Eltrombopag （EPAG）是一种小分子仿血小板生成素，先前已被证明可在难治性重度再生障碍性贫血（SAA）患者中产生持久的低毒性多谱系血液学反应。其在MAA中的安全性和有效性尚不清楚。这项前瞻性2期研究纳入了未经治疗和治疗的临床相关细胞减少的MAA和UC患者。EPAG的剂量从50 mg/d递增到300 mg/d。16 ~ 20周时评估血液学反应。有反应的患者继续进行EPAG治疗，直到达到定义的强健或稳定的血细胞计数。复发时重新使用EPAG。2012年至2017年期间，34名患者入组，其中31名患有MAA， 3名患有UC。到主要终点，17例患者在至少1个符合条件的谱系中有反应。在一个患有Diamond-Blackfan贫血症的病人身上观察到贫血的显著改善。EPAG耐受性良好，17例患者中有12例在中位8个月后血液计数强劲或稳定而停药。由于计数下降，大多数患者需要重新启动EPAG，并且所有患者都恢复了应答。34例患者中有2例在服用EPAG时出现非7号染色体骨髓细胞遗传学异常，未出现异常增生或母细胞增多。在EPAG上，癌症基因的体细胞突变等位基因频率总体上没有增加。EPAG是一种耐受良好的口服治疗MAA/UC患者细胞减少症的药物。
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.