A phase 2/3 multicenter randomized clinical trial of ABX-CBL versus ATG as secondary therapy for steroid-resistant acute graft-versus-host disease
A phase 2/3 multicenter randomized clinical trial of ABX-CBL versus ATG as secondary therapy for steroid-resistant acute graft-versus-host disease
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DOI：
10.1182/blood-2006-08-013995
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发表时间：
2007-03-15
期刊：
影响因子：
20.3
通讯作者：
Blazar, Bruce R.
中科院分区：
文献类型：
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作者：
MacMillan, Margaret L.;Couriel, Daniel;Blazar, Bruce R.
类固醇耐药的急性移植物抗宿主病（GVHD）的治疗取得了有限的成功。ABX-CBL是一种杂交瘤产生的抗CD 147抗原的鼠IgM单克隆抗体，在人白细胞上弱表达，在活化淋巴细胞上上调。在21个中心的95名患者中进行了一项前瞻性、多中心、开放标签、随机临床试验，比较ABX-CBL与抗胸腺细胞球蛋白（ATG）治疗类固醇耐药急性GVHD。48例患者连续14天每天接受ABX-CBL，随后每周两次接受长达6周的ABX-CBL。47例患者接受马ATG，30 mg/kg，每隔一天一次，共6次给药，根据需要增加疗程。到第180天，接受ABX-CBL的患者和接受ATG的患者的总体改善相似（56% vs 57%，P = 0.91）。ABX-CBL组18个月时的患者生存率不如ATG组（35% vs 45%），95%置信区间排除了ABX-CBL提供至少10.4%的改善。该试验的数据表明，ABX-CBL在治疗急性类固醇耐药GVHD方面并没有比ATG更好。这项针对激素耐药急性GVHD的前瞻性、多中心、随机临床试验可作为未来评估新药的模型。
Treatment for steroid-resistant acute graft-versus-host disease (GVHD) has had limited success. ABX-CBL is a hybridoma-generated murine IgM monoclonal antibody against the CD147 antigen, weakly expressed on human leukocytes and up-regulated on activated lymphocytes. A prospective, multicenter, open-label, randomized clinical trial comparing ABX-CBL to antithymocyte globulin (ATG) for treatment of steroid-resistant acute GVHD was conducted in 95 patients at 21 centers. Forty-eight patients received ABX-CBL daily for 14 consecutive days followed by up to 6 weeks of ABX-CBL twice weekly. Forty-seven patients received equine ATG, 30 mg/kg every other day for a total of 6 doses with additional courses as needed. By day 180, overall improvement was similar in the patients receiving ABX-CBL and in those receiving ATG (56% versus 57%, P = .91). Patient survival at 18 months was less favorable on ABX-CBL than on ATG (35% versus 45%), with the 95% confidence interval ruling out that ABX-CBL provides at least a 10.4% improvement. Data from this trial suggest that ABX-CBL does not offer an improvement over ATG in the treatment of acute steroid-resistant GVHD. This prospective, multicenter, randomized clinical trial for steroid-resistant acute GVHD serves as a model for future evaluation of new agents.