美国辛辛那提儿童医院医学中心Michael B. Jordan研究组近日取得新进展。他们发现Emapalumab可有效治疗儿童原发性噬血细胞淋巴组织细胞增多症。这一研究成果发表在2020年5月7日出版的《新英格兰医学杂志》上。
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.
Primary hemophagocytic lymphohistiocytosis is a rare syndrome characterized by immune dysregulation and hyperinflammation. It typically manifests in infancy and is associated with high mortality.
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.
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.
Emapalumab was an efficacious targeted therapy for patients with primary hemophagocytic lymphohistiocytosis.