Hematologic Disease Laboratory, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
Hematology Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
Blood. 2022 Jun 16;139(24):3493-3504. doi: 10.1182/blood.2021014860.
Hemophagocytic lymphohistiocytosis (HLH) is a lethal disorder characterized by hyperinflammation. Recently, ruxolitinib (RUX), targeting key cytokines in HLH, has shown promise for HLH treatment. However, there is a lack of robust clinical trials evaluating its efficacy, especially its utility as a frontline therapy. In this study (www.chictr.org.cn, ChiCTR2000031702), we designed ruxolitinib as a first-line agent for pediatric HLH and stratified the treatment based on its early response. Fifty-two newly diagnosed patients were enrolled. The overall response rate (ORR) of ruxolitinib monotherapy (day 28) was 69.2% (36/52), with 42.3% (22/52) achieving sustained complete remission (CR). All responders achieved their first response to ruxolitinib within 3 days. The response to ruxolitinib was significantly associated with the underlying etiology at enrollment (P = .009). Epstein-Barr virus (EBV)-HLH patients were most sensitive to ruxolitinib, with an ORR of 87.5% (58.3% in CR). After ruxolitinib therapy, 57.7% (30/52) of the patients entered intensive therapy with additional chemotherapy. Among them, 53.3% (16/30) patients achieved CR, and 46.7% (14/30) patients dominated by chronic active EBV infection-associated HLH (CAEBV-HLH) developed refractory HLH by week 8. The median interval to additional treatment since the first ruxolitinib administration was 6 days (range, 3-25 days). Altogether, 73.1% (38/52) of the enrolled patients achieved CR after treatment overall. The 12-month overall survival (OS) for all patients was 86.4% (95% confidence interval [CI], 77.1% to 95.7%). Ruxolitinib had low toxicity and was well tolerated compared with intensive chemotherapy. Our study provides clinical evidence for ruxolitinib as a frontline agent for pediatric HLH. The efficacy was particularly exemplified with stratified regimens based on the early differential response to ruxolitinib. This study was registered in the Chinese Clinical Trials Registry Platform (http://www.chictr.org.cn/) as ChiCTR2000031702.
噬血细胞性淋巴组织细胞增生症（HLH）是一种以炎症反应过度为特征的致命性疾病。最近，靶向 HLH 关键细胞因子的芦可替尼（RUX）在 HLH 治疗方面显示出了很好的效果。然而，目前缺乏评估其疗效的大型临床试验，尤其是其作为一线治疗的效用。在这项研究（www.chictr.org.cn，ChiCTR2000031702）中，我们设计将芦可替尼作为儿科 HLH 的一线药物，并根据其早期反应进行分层治疗。共纳入 52 例新诊断的患者。芦可替尼单药治疗（第 28 天）的总体缓解率（ORR）为 69.2%（36/52），42.3%（22/52）达到持续完全缓解（CR）。所有应答者均在 3 天内首次对芦可替尼产生应答。芦可替尼的反应与入组时的基础病因明显相关（P=0.009）。EBV-HLH 患者对芦可替尼最为敏感，ORR 为 87.5%（CR 为 58.3%）。芦可替尼治疗后，57.7%（52 例中有 30 例）的患者接受了强化化疗。其中，30 例中有 53.3%（16 例）达到 CR，而由慢性活动性 EBV 感染相关 HLH（CAEBV-HLH）引起的 46.7%（14 例）患者在第 8 周时出现难治性 HLH。从首次使用芦可替尼到接受额外治疗的中位间隔时间为 6 天（范围 3-25 天）。总体而言，52 例患者中有 73.1%（38 例）经治疗后达到 CR。所有患者的 12 个月总生存率（OS）为 86.4%（95%置信区间[CI]，77.1%至 95.7%）。与强化化疗相比，芦可替尼的毒性较低，且耐受性良好。本研究为芦可替尼作为儿科 HLH 的一线药物提供了临床证据。分层治疗方案基于芦可替尼早期的差异反应，疗效尤为显著。本研究在中国临床试验注册平台（http://www.chictr.org.cn/）注册，注册号为 ChiCTR2000031702。
