Emapalumab治療兒童原發性噬血細胞淋巴組織細胞增多症療效顯著
作者：
小柯機器人發布時間：2020/5/8 13:06:17
美國辛辛那提兒童醫院醫學中心Michael B. Jordan研究組近日取得新進展。他們發現Emapalumab可有效治療兒童原發性噬血細胞淋巴組織細胞增多症。這一研究成果發表在2020年5月7日出版的《新英格蘭醫學雜誌》上。
原發性噬血細胞淋巴組織細胞增多症是一種罕見的症候群，其特徵為免疫失調和過度炎症。它通常在嬰兒期出現，並伴有高死亡率。
研究組進行了一項開放標籤、單組、臨床2-3期研究，探討了Emapalumab（一種人抗幹??擾素γ抗體）與地塞米松聯用的的有效性和安全性，招募18歲以下且患有原發性噬血細胞淋巴組織細胞增多症的患者，包括入組前已接受常規治療（以前治療過）和未曾接受治療的患者。對患者進行長期隨訪，直到異基因造血幹細胞移植後1年，或如果未進行移植，則直到最後一次Emapalumab治療後1年。
截至2017年7月20日，共有34位患者接受了Emapalumab治療，27位此前接受過治療，7位未曾接受治療。26位患者完成了研究。63％先前接受過治療的患者和65％接受Emapalumab輸注的患者獲得緩解；這些百分比均顯著高於預先設定的40％的無效假設。
在先前接受過治療的患者中有70％能夠進行移植，而在接受Emapalumab治療的患者中有65％能夠進行移植。在最後一次觀察中，先前接受過治療的患者和接受Emapalumab治療的患者中分別有74％和71％仍存活。Emapalumab與任何器官毒性無關。Emapalumab治療期間有10例患者出現嚴重感染。1名患者因散發性組織胞漿菌病而停用Emapalumab。
總之，Emapalumab是治療原發性噬血細胞淋巴組織細胞增多症的有效靶向藥物。
附：英文原文
Title: Emapalumab in Children with Primary Hemophagocytic Lymphohistiocytosis
Author: Franco Locatelli, M.D.,, Michael B. Jordan, M.D.,, Carl Allen, M.D., Ph.D.,, Simone Cesaro, M.D.,, Carmelo Rizzari, M.D.,, Anupama Rao, M.D.,, Barbara Degar, M.D.,, Timothy P. Garrington, M.D.,, Julian Sevilla, M.D.,, Maria-Caterina Putti, M.D.,, Franca Fagioli, M.D.,, Martina Ahlmann, M.D.,, Jose-Luis Dapena Diaz, M.D.,, Michael Henry, M.D.,, Fabrizio De Benedetti, M.D., Ph.D.,, Alexei Grom, M.D.,, Genevieve Lapeyre, M.D.,, Philippe Jacqmin, Ph.D.,, Maria Ballabio, M.D.,, and Cristina de Min, M.D.
Issue&Volume: 2020-05-07
Abstract: Abstract
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.
DOI: NJ202005073821909
Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1911326