Brentuximab Vedotin (SGN-35) for Relapsed CD30-Positive Lymphomas.
Brentuximab Vedotin (SGN-35) for Relapsed CD30-Positive Lymphomas.
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DOI：
10.1056/nejmoa1002965
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发表时间：
2010-11-04
影响因子：
158.5
通讯作者：
Forero-Torres, Andres
中科院分区：
文献类型：
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作者：
Younes, Anas;Bartlett, Nancy L.;Forero-Torres, Andres
背景：霍奇金淋巴瘤和间变性大细胞淋巴瘤是两种最常见的表达CD 30的肿瘤。先前尝试用基于单克隆的疗法靶向CD 30抗原显示出最小的活性。为了增强CD 30导向治疗的抗肿瘤活性，通过酶可切割接头将抗微管蛋白剂单甲基澳瑞他汀E（MMAE）连接至CD 30特异性单克隆抗体，产生抗体-药物偶联物维布妥昔单抗（SGN-35）。在这项1期、开放标签、多中心剂量递增研究中，我们给予维布妥昔单抗（剂量为0.1 - 3.6 mg/kg体重），每3周一次给45名复发性或难治性CD 30阳性血液癌症患者，主要是霍奇金淋巴瘤和间变性大细胞淋巴瘤。患者接受了中位值为三个以前的化疗方案（范围，一到七），和73%经历了自体干细胞transplantation.Results：最大耐受剂量为1.8毫克每公斤，每3周给药。在17例患者中观察到客观缓解，包括11例完全缓解。在接受1.8 mg/kg剂量的12例患者中，6例（50%）有客观反应。中位缓解持续时间至少为9.7个月。在42例可评价的患者中，有36例（86%）观察到肿瘤消退。最常见的不良事件是疲劳，发热，腹泻，恶心，中性粒细胞减少症，和周围neuropathy.Conclusions：维布妥昔单抗诱导持久的客观反应，并导致肿瘤消退的复发性或难治性CD 30阳性淋巴瘤的大多数患者在这项1期研究。治疗主要与1级或2级（轻度至中度）毒性反应相关。（由西雅图遗传学公司资助; ClinicalTrials.gov编号，NCT 00430846。）新英格兰医学杂志2010;363：1812-21。
Background: Hodgkin's lymphoma and anaplastic large-cell lymphoma are the two most common tumors expressing CD30. Previous attempts to target the CD30 antigen with monoclonal-based therapies have shown minimal activity. To enhance the antitumor activity of CD30-directed therapy, the antitubulin agent monomethyl auristatin E (MMAE) was attached to a CD30-specific monoclonal antibody by an enzyme-cleavable linker, producing the antibody-drug conjugate brentuximab vedotin (SGN-35).Methods: In this phase 1, open-label, multicenter dose-escalation study, we administered brentuximab vedotin (at a dose of 0.1 to 3.6 mg per kilogram of body weight) every 3 weeks to 45 patients with relapsed or refractory CD30-positive hematologic cancers, primarily Hodgkin's lymphoma and anaplastic large-cell lymphoma. Patients had received a median of three previous chemotherapy regimens (range, one to seven), and 73% had undergone autologous stem-cell transplantation.Results: The maximum tolerated dose was 1.8 mg per kilogram, administered every 3 weeks. Objective responses, including 11 complete remissions, were observed in 17 patients. Of 12 patients who received the 1.8-mg-per-kilogram dose, 6 (50%) had an objective response. The median duration of response was at least 9.7 months. Tumor regression was observed in 36 of 42 patients who could be evaluated (86%). The most common adverse events were fatigue, pyrexia, diarrhea, nausea, neutropenia, and peripheral neuropathy.Conclusions: Brentuximab vedotin induced durable objective responses and resulted in tumor regression for most patients with relapsed or refractory CD30-positive lymphomas in this phase 1 study. Treatment was associated primarily with grade 1 or 2 (mild-to-moderate) toxic effects. (Funded by Seattle Genetics; ClinicalTrials.gov number, NCT00430846.)N Engl J Med 2010;363:1812-21.