BACKGROUND Primary hemophagocytic lymphohistiocytosis is a rare syndrome characterized by immune dysregulation and hyperinflammation. It typically manifests in infancy and is associated with high mortality. METHODS We investigated the efficacy and safety of emapalumab (a human anti-interferon-γ antibody), administered with dexamethasone, in an open-label, single-group, phase 2-3 study involving patients who had received conventional therapy before enrollment (previously treated patients) and previously untreated patients who were 18 years of age or younger and had primary hemophagocytic lymphohistiocytosis. The patients could enter a long-term follow-up study until 1 year after allogeneic hematopoietic stem-cell transplantation or until 1 year after the last dose of emapalumab, if transplantation was not performed. The planned 8-week treatment period could be shortened or extended if needed according to the timing of transplantation. The primary efficacy end point was the overall response, which was assessed in the previously treated patients according to objective clinical and laboratory criteria. RESULTS At the cutoff date of July 20, 2017, a total of 34 patients (27 previously treated patients and 7 previously untreated patients) had received emapalumab; 26 patients completed the study. A total of 63% of the previously treated patients and 65% of the patients who received an emapalumab infusion had a response; these percentages were significantly higher than the prespecified null hypothesis of 40% (P = 0.02 and P = 0.005, respectively). In the previously treated group, 70% of the patients were able to proceed to transplantation, as were 65% of the patients who received emapalumab. At the last observation, 74% of the previously treated patients and 71% of the patients who received emapalumab were alive. Emapalumab was not associated with any organ toxicity. Severe infections developed in 10 patients during emapalumab treatment. Emapalumab was discontinued in 1 patient because of disseminated histoplasmosis. CONCLUSIONS Emapalumab was an efficacious targeted therapy for patients with primary hemophagocytic lymphohistiocytosis. (Funded by NovImmune and the European Commission; NI-0501-04 and NI-0501-05 ClinicalTrials.gov numbers, NCT01818492 and NCT02069899.).

中文翻译：

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Emapalumab 在儿童原发性噬血细胞淋巴组织细胞增生症中的应用。

背景原发性噬血细胞淋巴组织细胞增生症是一种罕见的综合征，其特征是免疫失调和过度炎症。它通常出现在婴儿期，并且与高死亡率有关。方法 我们在一项开放标签、单组、2-3 期研究中研究了 emapalumab（一种人类抗干扰素 γ 抗体）与地塞米松联合给药的疗效和安全性，该研究涉及在入组前接受过常规治疗的患者（之前为治疗的患者）和既往未治疗的 18 岁或以下且患有原发性噬血细胞淋巴组织细胞增生症的患者。如果未进行移植，患者可以进入长期随访研究，直至异基因造血干细胞移植后 1 年或最后一剂 emapalumab 后 1 年。根据移植时机的需要，可缩短或延长计划的8周治疗期。主要疗效终点是总体反应，根据客观临床和实验室标准在先前治疗的患者中进行评估。结果 在截止日期 2017 年 7 月 20 日，共有 34 名患者（27 名既往接受过治疗的患者和 7 名未接受过治疗的患者）接受了 emapalumab；26 名患者完成了研究。共有 63% 的既往治疗患者和 65% 接受 emapalumab 输注的患者有反应；这些百分比显着高于预先指定的 40% 的零假设（分别为 P = 0.02 和 P = 0.005）。在先前治疗的组中，70% 的患者能够进行移植，65% 的接受 emapalumab 的患者也是如此。在最后一次观察中，74% 的先前接受治疗的患者和 71% 接受 emapalumab 的患者存活。Emapalumab 与任何器官毒性无关。10 名患者在 emapalumab 治疗期间发生严重感染。1 名患者因播散性组织胞浆菌病停用 Emapalumab。结论 Emapalumab 是一种有效的靶向治疗原发性噬血细胞性淋巴组织细胞增生症患者。（由 NovImmune 和欧盟委员会资助；NI-0501-04 和 NI-0501-05 ClinicalTrials.gov 编号，NCT01818492 和 NCT02069899。）。10 名患者在 emapalumab 治疗期间发生严重感染。1 名患者因播散性组织胞浆菌病停用 Emapalumab。结论 Emapalumab 是一种有效的靶向治疗原发性噬血细胞性淋巴组织细胞增生症患者。（由 NovImmune 和欧盟委员会资助；NI-0501-04 和 NI-0501-05 ClinicalTrials.gov 编号，NCT01818492 和 NCT02069899。）。10 名患者在 emapalumab 治疗期间发生严重感染。1 名患者因播散性组织胞浆菌病停用 Emapalumab。结论 Emapalumab 是一种有效的靶向治疗原发性噬血细胞性淋巴组织细胞增生症患者。（由 NovImmune 和欧盟委员会资助；NI-0501-04 和 NI-0501-05 ClinicalTrials.gov 编号，NCT01818492 和 NCT02069899。）。