本妥昔单抗用于CD30+外周T细胞淋巴瘤患者一线治疗：一项I期研究结果
Brentuximab vedotin in the front-line treatment of patients with CD30+ peripheral T-cell lymphomas: results of a phase I study.
作者信息
Fanale Michelle A, Horwitz Steven M, Forero-Torres Andres, Bartlett Nancy L, Advani Ranjana H, Pro Barbara, Chen Robert W, Davies Andrew, Illidge Tim, Huebner Dirk, Kennedy Dana A, Shustov Andrei R
机构信息
Michelle A. Fanale, The University of Texas MD Anderson Cancer Center, Houston, TX; Steven M. Horwitz, Memorial Sloan-Kettering Cancer Center, New York, NY; Andres Forero-Torres, University of Alabama at Birmingham, Birmingham, AL; Nancy L. Bartlett, Washington University School of Medicine, St Louis, MO; Ranjana H. Advani, Stanford University Medical Center, Palo Alto; Robert W. Chen, City of Hope National Medical Center, Duarte, CA; Barbara Pro, Fox Chase Cancer Center, Philadelphia, PA; Dirk Huebner, Takeda Pharmaceuticals International, Cambridge, MA; Dana A. Kennedy, Seattle Genetics, Bothell; Andrei R. Shustov, University of Washington Medical Center, Seattle, WA; Andrew Davies, University of Southampton School of Medicine, Southampton; Tim Illidge, Institute of Cancer Sciences, University of Manchester, Manchester, United Kingdom.
出版信息
J Clin Oncol. 2014 Oct 1;32(28):3137-43. doi: 10.1200/JCO.2013.54.2456. Epub 2014 Aug 18.
PURPOSE
Front-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 METHODS
Patients 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.
RESULTS
After 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%).
CONCLUSION
Brentuximab 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).
目的
外周T细胞淋巴瘤（PTCL）的一线治疗方案包括环磷酰胺、阿霉素、长春新碱、泼尼松（CHOP）方案，其5年总生存率（OS）低于50%。这项I期开放标签研究评估了在CD30(+) PTCL患者中，一线治疗时，本妥昔单抗与CHOP序贯使用或与CHP（不含长春新碱的CHOP）联合使用的安全性和活性。
患者与方法
患者接受序贯治疗（每３周一次），先使用1.8mg/kg本妥昔单抗（两个周期），随后使用CHOP（六个周期），或使用1.8mg/kg本妥昔单抗加CHP（BV+CHP）六个周期（每３周一次）。缓解者接受单药本妥昔单抗额外治疗8至10个周期（共16个周期）。主要目标是评估安全性；次要终点包括客观缓解率、完全缓解（CR）率、无进展生存率（PFS）和OS。两种治疗方法未进行预先设定的比较。
结果
序贯治疗后，13例患者中有11例（85%）获得客观缓解（CR率为62%；估计1年PFS率为77%）。13例患者中有8例（62%）发生3/4级不良事件。联合治疗结束时，所有患者（n = 26）均获得客观缓解（CR率为88%；估计1年PFS率为71%）。所有7例无间变性大细胞淋巴瘤的患者均达到CR。联合治疗组中发生率≥10%的3/4级不良事件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
本妥昔单抗与CHOP序贯使用或与CHP联合使用时，安全性可控，在新诊断的CD30(+) PTCL患者中显示出显著的抗肿瘤活性。一项随机III期试验正在进行中，比较BV+CHP与CHOP（临床试验编号：NCT01777152）。
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