Results of a Pivotal Phase II Study of Brentuximab Vedotin for Patients With Relapsed or Refractory Hodgkin's Lymphoma
Results of a Pivotal Phase II Study of Brentuximab Vedotin for Patients With Relapsed or Refractory Hodgkin's Lymphoma
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DOI：
10.1200/jco.2011.38.0410
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发表时间：
2012-06-20
影响因子：
45.3
通讯作者：
Chen, Robert
中科院分区：
文献类型：
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作者：
Younes, Anas;Gopal, Ajay K.;Chen, Robert
目的brentuximab vedotin是一种抗体-药物偶联物（ADC），可选择性地将单甲基auristatin E（一种抗菌素小管剂）递送到表达cd30的细胞中。在I期研究中，brentuximab vedotin在复发或难治性cd30阳性淋巴瘤患者中显示出显著的活性和良好的安全性。在这项跨国、开放标签、II期研究中，研究人员评估了brentuximab vedotin在自体干细胞移植（auto-SCT）后复发或难治性霍奇金淋巴瘤（HL）患者中的疗效和安全性。通过中心病理检查，患者有组织学记录的cd30阳性HL。102例患者接受brentuximab vedotin 1.8 mg/kg静脉滴注，每3周一次。在没有疾病进展或禁忌性毒性的情况下，患者最多接受16个周期的治疗。主要终点是由独立放射学审查机构确定的总体客观缓解率（ORR）。结果34%的患者ORR为75%，完全缓解（CR）。所有患者的中位无进展生存期为5.6个月，CR患者的中位缓解持续时间为20.5个月。中位观察时间超过1.5年，31名患者存活，无进展性疾病记录。最常见的治疗相关不良事件是周围感觉神经病变、恶心、疲劳、中性粒细胞减少和腹泻。结论ADC brentuximab vedotin在75%的复发或难治性HL患者中具有可控的毒性和诱导的客观反应。观察到接近2年的持久cr，支持早期治疗线的研究。[J]中华临床杂志，30(3):583 - 589。(c) 2012年由美国临床肿瘤学会发布
PurposeBrentuximab vedotin is an antibody-drug conjugate (ADC) that selectively delivers monomethyl auristatin E, an antimicrotubule agent, into CD30-expressing cells. In phase I studies, brentuximab vedotin demonstrated significant activity with a favorable safety profile in patients with relapsed or refractory CD30-positive lymphomas.Patients and MethodsIn this multinational, open-label, phase II study, the efficacy and safety of brentuximab vedotin were evaluated in patients with relapsed or refractory Hodgkin's lymphoma (HL) after autologous stem-cell transplantation (auto-SCT). Patients had histologically documented CD30-positive HL by central pathology review. A total of 102 patients were treated with brentuximab vedotin 1.8 mg/kg by intravenous infusion every 3 weeks. In the absence of disease progression or prohibitive toxicity, patients received a maximum of 16 cycles. The primary end point was the overall objective response rate (ORR) determined by an independent radiology review facility.ResultsThe ORR was 75% with complete remission (CR) in 34% of patients. The median progression-free survival time for all patients was 5.6 months, and the median duration of response for those in CR was 20.5 months. After a median observation time of more than 1.5 years, 31 patients were alive and free of documented progressive disease. The most common treatment-related adverse events were peripheral sensory neuropathy, nausea, fatigue, neutropenia, and diarrhea.ConclusionThe ADC brentuximab vedotin was associated with manageable toxicity and induced objective responses in 75% of patients with relapsed or refractory HL after auto-SCT. Durable CRs approaching 2 years were observed, supporting study in earlier lines of therapy. J Clin Oncol 30:2183-2189. (c) 2012 by American Society of Clinical Oncology