Division of Bone Marrow Transplant, Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University, Atlanta, GA.
Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
Blood Adv. 2024 May 14;8(9):2248-2258. doi: 10.1182/bloodadvances.2023012217.
Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening, hyperinflammatory syndrome. Emapalumab, a fully human monoclonal antibody that neutralizes the proinflammatory cytokine interferon gamma, is approved in the United States to treat primary HLH (pHLH) in patients with refractory, recurrent, or progressive disease, or intolerance with conventional HLH treatments. REAL-HLH, a retrospective study, conducted across 33 US hospitals, evaluated real-world treatment patterns and outcomes in patients treated with ≥1 dose of emapalumab between 20 November 2018 and 31 October 2021. In total, 46 patients met the pHLH classification criteria. Median age at diagnosis was 1.0 year (range, 0.3-21.0). Emapalumab was initiated for treating refractory (19/46), recurrent (14/46), or progressive (7/46) pHLH. At initiation, 15 of 46 patients were in the intensive care unit, and 35 of 46 had received prior HLH-related therapies. Emapalumab treatment resulted in normalization of key laboratory parameters, including chemokine ligand 9 (24/33, 72.7%), ferritin (20/45, 44.4%), fibrinogen (37/38, 97.4%), platelets (39/46, 84.8%), and absolute neutrophil count (40/45, 88.9%). Forty-two (91.3%) patients were considered eligible for transplant. Pretransplant survival was 38 of 42 (90.5%). Thirty-one (73.8%) transplant-eligible patients proceeded to transplant, and 23 of 31 (74.2%) of those who received transplant were alive at the end of the follow-up period. Twelve-month survival probability from emapalumab initiation for the entire cohort (N = 46) was 73.1%. There were no discontinuations because of adverse events. In conclusion, results from the REAL-HLH study, which describes treatment patterns, effectiveness, and outcomes in patients with pHLH treated with emapalumab in real-world settings, are consistent with the emapalumab pivotal phase 2/3 pHLH trial.
噬血细胞性淋巴组织细胞增生症(HLH)是一种罕见的、危及生命的、过度炎症综合征。emapalumab 是一种完全人源化的单克隆抗体,可中和促炎细胞因子干扰素 γ,已获美国批准用于治疗难治性、复发性或进行性疾病或不耐受常规 HLH 治疗的原发性 HLH(pHLH)患者。REAL-HLH 是一项回顾性研究,在 33 家美国医院进行,评估了 2018 年 11 月 20 日至 2021 年 10 月 31 日期间接受≥1 剂 emapalumab 治疗的患者的真实世界治疗模式和结局。共有 46 名患者符合 pHLH 分类标准。诊断时的中位年龄为 1.0 岁(范围,0.3-21.0)。emapalumab 用于治疗难治性(19/46)、复发性(14/46)或进行性(7/46)pHLH。起始时,46 例患者中有 15 例在重症监护病房,35 例患者接受了既往 HLH 相关治疗。emapalumab 治疗使关键实验室参数正常化,包括趋化因子配体 9(24/33,72.7%)、铁蛋白(20/45,44.4%)、纤维蛋白原(37/38,97.4%)、血小板(39/46,84.8%)和绝对中性粒细胞计数(40/45,88.9%)。42 例(91.3%)患者被认为有移植资格。移植前存活率为 42 例中的 38 例(90.5%)。31 例(73.8%)有移植资格的患者进行了移植,其中 31 例中的 23 例(74.2%)在随访结束时存活。整个队列(N=46)从 emapalumab 起始的 12 个月生存率为 73.1%。无因不良事件而停药。总之,REAL-HLH 研究的结果描述了在真实环境中使用 emapalumab 治疗 pHLH 患者的治疗模式、有效性和结局,与 emapalumab 关键性 2/3 期 pHLH 试验的结果一致。