Ruxolitinib combined with etanercept induce a rapid response to corticosteroid-refractory severe acute graft vs host disease after allogeneic stem cell transplantation: Results of a multi-center prospective study
Ruxolitinib combined with etanercept induce a rapid response to corticosteroid-refractory severe acute graft vs host disease after allogeneic stem cell transplantation: Results of a multi-center prospective study
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鲁索替尼联合依那西普在同种异体干细胞移植后诱导对皮质类固醇难治性严重急性移植物抗宿主病的快速反应：多中心前瞻性研究的结果
DOI：
10.1002/ajh.25898
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发表时间：
2020-07-06
影响因子：
12.8
通讯作者：
Huang, He
中科院分区：
文献类型：
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作者：
Zhao, Yanmin;Wu, Hengwei;Huang, He
大约一半的严重急性移植物抗宿主病（aGVHD）患者对一线类固醇治疗表现出耐药性。我们招募了64例异基因造血干细胞移植（allo-SCT）后的III-IV级SR-aGVHD患者，以评估鲁索利替尼和依那西普联合治疗的疗效和安全性。联合治疗第28天的总缓解率为87.5%（95% CI，79.7%-95.3%），其中73.4%达到完全缓解（CR）。在第28天，75.4%的患者记录到每日皮质类固醇剂量显著减少>= 75%。从aGVHD到鲁索利替尼的延迟时间（OR = 4.88，95%CI，0.98-23.56）、3-4期肝脏aGVHD（OR = 8.57，95%CI，0.96-46.59）和肠道肠杆菌定植（OR = 12.39，95%CI，1.71-59.77）与不完全缓解相关。在29.7%、26.6%、39.1%和50.0%的患者中分别发现3/4级贫血、白细胞减少或血小板减少和CMV再激活。25例（39.1%）出现≥ 3级严重感染并发症，其中肺部感染最多见（15/64，23.4%）。联合治疗后2年总生存率为61.2%。2年非复发死亡率和基础恶性肿瘤复发率分别为26.7%和15.7%。鲁索利替尼联合依那西普治疗重度aGVHD患者安全有效，但各种感染并发症值得重视。本研究已在中国临床试验注册中心（ChiCTR 1900024408）注册。
About half of patients with severe acute graft vs host disease (aGVHD) show resistance to treatment with first-line steroids. We enrolled 64 patients with grades III-IV SR-aGVHD after allogeneic hematopoietic stem cell transplantation (allo-SCT), to assess the efficacy and safety of the combination therapy of ruxolitinib and etanercept. The overall response rate was 87.5% (95% CI, 79.7%-95.3%) at day 28 of the combination treatment, from which 73.4% reached complete response (CR). A marked reduction >= 75% in daily corticosteroid dosing was documented in 75.4% of patients at day 28. Delayed time from aGVHD to ruxolitinib (OR = 4.88, 95% CI, 0.98-23.56), stages 3-4 liver aGVHD (OR = 8.57, 95% CI, 0.96-46.59) and gutEnterobacteriaceaecolonization (OR = 12.39, 95% CI, 1.71-59.77) were related to incomplete response. Grades 3/4 anemia, leukopenia, or thrombocytopenia and CMV-reactivation were found in 29.7%, 26.6%, 39.1%, and 50.0% of patients, respectively. So, 25 (39.1%) experienced complications of severe infection >= 3 grade, in which pulmonary infections were most frequent (15/64, 23.4%). The 2-year overall survival (OS) after the combination therapy was 61.2%. The 2-year incidence of non-relapse mortality and relapse of the underlying malignancy was 26.7% and 15.7%, respectively. Combined treatment with ruxolitinib and etanercept was very effective and relatively safe for severe aGVHD patients, while the various infection complications deserve more attention. This study was registered at the Chinese Clinical Trial Registry (ChiCTR1900024408).