Brentuximab Vedotin in the Front-Line Treatment of Patients With CD30+ Peripheral T-Cell Lymphomas: Results of a Phase I Study
Brentuximab Vedotin in the Front-Line Treatment of Patients With CD30+ Peripheral T-Cell Lymphomas: Results of a Phase I Study
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DOI：
10.1200/jco.2013.54.2456
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发表时间：
2014-10-01
影响因子：
45.3
通讯作者：
Shustov, Andrei R.
中科院分区：
文献类型：
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作者：
Fanale, Michelle A.;Horwitz, Steven M.;Shustov, Andrei R.
外周T细胞淋巴瘤（PTCL）的一线治疗包括环磷酰胺、阿霉素、长春新碱、泼尼松（CHOP）等方案，其5年总生存率（OS）低于50%。这项I期开放标签研究评价了维布妥昔单抗与CHOP序贯给药或与CHP联合给药的安全性和活性（CHOP无长春新碱）作为一线治疗CD 30（+）PTCL患者。患者和方法患者接受序贯治疗维布妥昔单抗1.8 mg/kg（每3周一次）（2个周期），随后为CHOP（6个周期）或维布妥昔单抗1.8 mg/kg + CHP（BV + CHP），持续6个周期（每3周一次）。应答者接受维布妥昔单抗单药治疗8 - 10个额外周期（共16个周期）。主要目的是评估的安全性;次要终点包括客观反应率，完全缓解（CR）率，无进展生存率（PFS），和OS. There是没有预先规定的比较两种治疗approximates.ResultsAfter序贯治疗，11（85%）的13例患者达到了客观反应（CR率，62%;估计1年PFS率，77%）。13例患者中有8例（62%）发生了3/4级不良事件。在联合治疗结束时，所有患者（n = 26）均达到客观缓解（CR率，88%;估计1年PFS率，71%）。所有7例无间变性大细胞淋巴瘤的患者均达到CR。联合治疗组中3/4级不良事件（≥ 10%）为发热性中性粒细胞减少（31%）、中性粒细胞减少（23%）、贫血（15%）和肺栓塞（12%）。结论维布妥昔单抗与CHOP序贯给药或与CHP联合给药具有可管理的安全性特征，在新诊断的CD 30（+）PTCL患者中显示出显著的抗肿瘤活性。正在进行一项随机III期试验，比较BV + CHP与CHOP（临床试验编号NCT 01777152）。(C)2014年美国临床肿瘤学会
PurposeFront-line treatment of peripheral T-cell lymphomas (PTCL) involves regimens such as cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) and results in a 5-year overall survival (OS) rate of less than 50%. This phase I open-label study evaluated the safety and activity of brentuximab vedotin administered sequentially with CHOP or in combination with CHP (CHOP without vincristine) as front-line treatment in patients with CD30(+) PTCL.Patients and MethodsPatients received sequential treatment (once every 3 weeks) with brentuximab vedotin 1.8 mg/kg (two cycles) followed by CHOP (six cycles) or brentuximab vedotin 1.8 mg/kg plus CHP (BV + CHP) for six cycles (once every 3 weeks). Responders received single-agent brentuximab vedotin for eight to 10 additional cycles (for a total of 16 cycles). The primary objective was assessment of safety; secondary end points included objective response rate, complete remission (CR) rate, progression-free survival rate (PFS), and OS. There were no prespecified comparisons of the two treatment approaches.ResultsAfter sequential treatment, 11 (85%) of 13 patients achieved an objective response (CR rate, 62%; estimated 1-year PFS rate, 77%). Grade 3/4 adverse events occurred in eight (62%) of 13 patients. At the end of combination treatment, all patients (n = 26) achieved an objective response (CR rate, 88%; estimated 1-year PFS rate, 71%). All seven patients without anaplastic large-cell lymphoma achieved CR. Grade 3/4 adverse events (>= 10%) in the combination-treatment group were febrile neutropenia (31%), neutropenia (23%), anemia (15%), and pulmonary embolism (12%).ConclusionBrentuximab vedotin, administered sequentially with CHOP or in combination with CHP, had a manageable safety profile and exhibited substantial antitumor activity in newly diagnosed patients with CD30(+) PTCL. A randomized phase III trial is under way, comparing BV + CHP with CHOP (clinical trial No. NCT01777152). (C) 2014 by American Society of Clinical Oncology