Antithymocyte globulin (ATG)-based immunosuppression is standard in front-line treatment for people with severe aplastic anaemia without a histocompatible donor or who are 40 years or older. However, ATG requires in-hospital administration, is associated with infusion-related toxicities and has limited availability worldwide. In this study, we investigated the activity and safety of an ATG-free regimen of eltrombopag with cyclosporin A as a potential treatment for patients with severe aplastic anaemia who might not have access to or cannot tolerate horse-ATG. SOAR was a multicentre, single-arm phase 2 trial investigating eltrombopag and cyclosporin in adult (≥18 years) patients with severe aplastic anaemia who were treatment-naive and had an Eastern Cooperative Oncology Group performance status of less than 2. Participants were recruited from 20 hospitals in ten countries. Eltrombopag was initiated at 150 mg (100 mg in patients of Asian ethnicity) and cyclosporin at 10 mg/kg per day (adjusted to a trough of 200–400 μg/L) orally from day 1 to 6 months. The primary outcome was an overall haematological response rate by 6 months in the intention-to-treat population. This is the final report of the primary analysis period. The trial was registered with , , and has been completed. 54 patients were enrolled between May 11, 2017, and March 23, 2020. 34 (63%) patients were male and 20 (37%) were female. 22 (41%) were Asian, 22 (41%) were White, one (2%) was Native American or Alaska Native, one (2%) was Black or African American, and eight (15%) were other race or ethnicity. 35 patients (65%) completed 6 months of treatment with eltrombopag and cyclosporin and six (11%) completed the cyclosporin tapering period up to month 24. Overall haematological response rate by month 6 of treatment was 46% (25 of 54; 95% CI 33–60). The most reported adverse events were increased serum bilirubin (in 22 patients [41%]), nausea (16 [30%]), increased alanine aminotransferase concentration (12 [22%]), and diarrhoea (12 [22%]). Eight patients died on-treatment, but no deaths were considered related to the treatment. Eltrombopag and cyclosporin was active as front-line treatment of severe aplastic anaemia, with no unexpected safety concerns. This approach might be beneficial where horse-ATG is not available or not tolerated. Novartis Pharmaceuticals.

中文翻译：

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艾曲波帕联合环孢素 A 作为成人严重再生障碍性贫血 (SOAR) 一线治疗的活性和安全性：2 期单臂研究

基于抗胸腺细胞球蛋白 (ATG) 的免疫抑制是无组织相容性供体的严重再生障碍性贫血患者或 40 岁或以上患者的一线治疗标准。然而，ATG 需要在医院内给药，与输液相关的毒性有关，并且在全球范围内的可用性有限。在这项研究中，我们研究了艾曲波帕联合环孢菌素 A 的无 ATG 方案的活性和安全性，作为可能无法获得或不能耐受马 ATG 的严重再生障碍性贫血患者的潜在治疗方法。SOAR 是一项多中心、单组 2 期试验，研究艾曲波帕和环孢素治疗未接受治疗且东部肿瘤合作组表现状态低于 2 的严重再生障碍性贫血成人（≥18 岁）患者。参与者招募自十个国家的 20 家医院。从第 1 天到第 6 个月，艾曲波帕的起始剂量为 150 mg（亚洲患者为 100 mg），环孢素的剂量为每天 10 mg/kg（调整至 200-400 μg/L 的谷值）。主要结局是意向治疗人群 6 个月时的总体血液学缓解率。这是初步分析期的最终报告。该试验已在 、 、 注册，并已完成。2017年5月11日至2020年3月23日期间入组了54名患者。其中34名患者（63%）为男性，20名患者（37%）为女性。22 名 (41%) 为亚洲人，22 名 (41%) 为白人，1 名 (2%) 为美洲原住民或阿拉斯加原住民，1 名 (2%) 为黑人或非裔美国人，8 名 (15%) 为其他种族或民族。35 名患者 (65%) 完成了 6 个月的艾曲波帕和环孢素治疗，6 名患者 (11%) 完成了直至第 24 个月的环孢菌素逐渐减量期。治疗第 6 个月的总体血液学缓解率为 46%（54 名患者中的 25 名；95%） CI 33-60）。报告最多的不良事件是血清胆红素升高（22 例患者 [41%]）、恶心（16 例 [30%]）、丙氨酸转氨酶浓度升高（12 例 [22%]）和腹泻（12 例 [22%]）。八名患者在治疗期间死亡，但没有死亡被认为与治疗有关。艾曲波帕和环孢菌素是严重再生障碍性贫血的一线治疗药物，没有出现意外的安全问题。当马 ATG 不可用或不耐受时，这种方法可能会很有用。诺华制药。