Eltrombopag Added to Standard Immunosuppression for Aplastic Anemia.
Eltrombopag Added to Standard Immunosuppression for Aplastic Anemia.
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DOI：
10.1056/nejmoa1613878
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发表时间：
2017-04-20
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影响因子：
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通讯作者：
Young NS
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作者：
Townsley DM;Scheinberg P;Winkler T;Desmond R;Dumitriu B;Rios O;Weinstein B;Valdez J;Lotter J;Feng X;Desierto M;Leuva H;Bevans M;Wu C;Larochelle A;Calvo KR;Dunbar CE;Young NS
获得性再生障碍性贫血是由于免疫介导的骨髓破坏。免疫抑制疗法是有效的，但减少残留干细胞的数量可能会限制其疗效。在免疫抑制难治性再生障碍性贫血患者中，艾曲泊帕（一种合成血小板生成素受体激动剂）导致几乎一半患者的血细胞计数出现具有临床意义的升高。我们将标准免疫抑制治疗与艾曲泊帕联合用于既往未经治疗的重度再生障碍性贫血患者。我们在一项免疫抑制治疗加艾曲泊帕的前瞻性1 - 2期研究中入组了92例连续患者。3个连续入组队列在艾曲泊帕治疗方案的开始时间和持续时间方面存在差异（队列1从第14天至6个月接受艾曲泊帕治疗，队列2从第14天至3个月接受艾曲泊帕治疗，队列3从第1天至6个月接受艾曲泊帕治疗）。单独分析队列。主要结局为6个月时的完全血液学缓解。次要终点包括总体缓解、生存期、复发和髓系癌的克隆演变。队列1、队列2和队列3的6个月完全缓解率分别为33%、26%和58%。6个月时的总体缓解率分别为80%、87%和94%。合并队列的完全缓解率和总体缓解率高于我们的历史队列，其中完全缓解率为10%，总体缓解率为66%。中位随访时间为2年，生存率为97%; 1例患者在研究期间死于非血液学原因。观察到骨髓细胞结构、CD 34+细胞数量和早期造血祖细胞频率显著增加。复发率和克隆进化率与我们的历史经验相似。2例患者发生重度皮疹，导致提前停用艾曲泊帕。在免疫抑制治疗中添加艾曲泊帕与重度再生障碍性贫血患者的血液学应答率显著高于历史队列相关。（由国家心肺血液研究所资助; www.example.com编号，NCT 01623167。
Acquired aplastic anemia results from immune-mediated destruction of bone marrow. Immunosuppressive therapies are effective, but reduced numbers of residual stem cells may limit their efficacy. In patients with aplastic anemia that was refractory to immunosuppression, eltrombopag, a synthetic thrombopoietin-receptor agonist, led to clinically significant increases in blood counts in almost half the patients. We combined standard immunosuppressive therapy with eltrombopag in previously untreated patients with severe aplastic anemia. We enrolled 92 consecutive patients in a prospective phase 1–2 study of immunosuppressive therapy plus eltrombopag. The three consecutively enrolled cohorts differed with regard to the timing of initiation and the duration of the eltrombopag regimen (cohort 1 received eltrombopag from day 14 to 6 months, cohort 2 from day 14 to 3 months, and cohort 3 from day 1 to 6 months). The cohorts were analyzed separately. The primary outcome was complete hematologic response at 6 months. Secondary end points included overall response, survival, relapse, and clonal evolution to myeloid cancer. The rate of complete response at 6 months was 33% in cohort 1, 26% in cohort 2, and 58% in cohort 3. The overall response rates at 6 months were 80%, 87%, and 94%, respectively. The complete and overall response rates in the combined cohorts were higher than in our historical cohort, in which the rate of complete response was 10% and the overall response rate was 66%. At a median follow-up of 2 years, the survival rate was 97%; one patient died during the study from a nonhematologic cause. Marked increases in bone marrow cellularity, CD34+ cell number, and frequency of early hematopoietic progenitors were noted. Rates of relapse and clonal evolution were similar to our historical experience. Severe rashes occurred in two patients, resulting in the early discontinuation of eltrombopag. The addition of eltrombopag to immunosuppressive therapy was associated with markedly higher rates of hematologic response among patients with severe aplastic anemia than in a historical cohort. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT01623167.)