Combining therapeutic antibodies using basiliximab and etanercept for severe steroid-refractory acute graft-versus-host disease: A multi-center prospective study
Combining therapeutic antibodies using basiliximab and etanercept for severe steroid-refractory acute graft-versus-host disease: A multi-center prospective study
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使用巴利昔单抗和依那西普联合治疗抗体治疗严重类固醇难治性急性移植物抗宿主病：一项多中心前瞻性研究
DOI：
10.1080/2162402x.2016.1277307
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发表时间：
2017-01-01
期刊：
影响因子：
7.2
通讯作者：
Huang, He
中科院分区：
文献类型：
--
作者：
Tan, Yamin;Xiao, Haowen;Huang, He
同种异体造血干细胞移植后，急性移植与宿主疾病（AGVHD）仍然是一个主要问题。 AGVHD的标准前线治疗涉及皮质类固醇。但是，不到一半的患者有持久的完全反应。类固醇难治性AGVHD（SR-AGVHD）的长期死亡率仍约为70％。迄今为止，关于SR-AGVHD的最佳打捞处理尚未达成共识。我们进行了第一个前瞻性，多中心的临床试验，以评估一种新型方法的疗效和安全性，用于治疗严重的（III-IV级）SR-AGVHD与basiliximab和etanercept的组合。包括六个中心的65例严重SR-AGVHD患者。大昔单抗输注的中位数为4（范围2-11），etanercept的中位数为9（范围2-12）。在开始组合处理后的第28天，对二线治疗的总体反应（完全和部分响应：CRCPR）为90.8％，CR 75.4％。皮肤，肝脏和肠道受累分别为100％，73.8％和79.7％。患者> 30岁（p = 0.043，RR = 3.169），III-IV肝AGVHD（P = 0.007，RR = 5.034）和巨细胞病毒（CMV）重新激活（P = 0.035，RR = 4.02）的患者是独立的预测因子。与经典的救助治疗相比，与大律师和依然酸酯的结合治疗可改善CR对内脏AGVHD的CR改善，并具有明显优于2-y的总生存率（54.7％vs. 14.8％，p <0.001）。我们的数据表明，大律师和依然酸酯的结合可能构成SR-AGVHD的新型治疗选择。
Acute graft versus host disease (aGVHD) remains a major problem after allogeneic hematopoietic stem cell transplantation. Standard frontline therapy for aGVHD involves corticosteroids. However, fewer than half of patients have a lasting complete response. The long-term mortality rate of steroid-refractory aGVHD (SR-aGVHD) remains around 70%. To date, no consensus has been reached regarding the optimal salvage treatment for SR-aGVHD. We performed the first prospective, multi-center clinical trial to assess the efficacy and safety of a novel approach to treat severe (grades III-IV) SR-aGVHD with the combination of basiliximab and etanercept. Sixty-five patients with severe SR-aGVHD from six centers were included. The median number of basiliximab infusions was 4 (range 2-11) and of etanercept was 9 (range 2-12). At day 28 after starting the combination treatment, overall response (complete and partial response: CRCPR) to second-line treatment was 90.8% with 75.4% being CR. The incidences of CR per organ were 100%, 73.8%, and 79.7% for skin, liver, and gut involvement, respectively. Patients >30-y old (p = 0.043, RR = 3.169), development of grades III-IV liver aGVHD (p = 0.007, RR = 5.034) and cytomegalovirus (CMV) reactivation (p = 0.035, RR = 4.02) were independent predictors for incomplete response. Combined treatment with basiliximab and etanercept resulted in improved CR to visceral aGVHD and significantly superior 2-y overall survival (54.7% vs. 14.8%, p < 0.001) compared with classical salvage treatments. Our data suggest that the combination of basiliximab and etanercept may constitute a promising new treatment option for SR-aGVHD.