Belinostat in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma: Results of the Pivotal Phase II BELIEF (CLN-19) Study
Belinostat in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma: Results of the Pivotal Phase II BELIEF (CLN-19) Study
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DOI：
10.1200/jco.2014.59.2782
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发表时间：
2015-08-10
影响因子：
45.3
通讯作者：
Shustov, Andrei
中科院分区：
文献类型：
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作者：
O'Connor, Owen A.;Horwitz, Steven;Shustov, Andrei
外周T细胞淋巴瘤(PTCL)是一种多种多样的非霍奇金淋巴瘤，预后较差，对复发或难治性疾病患者没有公认的治疗标准。这项研究评估了一种新型的组蛋白去乙酰化酶抑制剂贝力诺斯特作为单一药物治疗复发或难治性PTCL的有效性和耐受性。患者和方法确诊为PTCL的患者在既往一次治疗后出现进展的患者接受贝力诺斯特1000 mg/m(2)作为每日30分钟的输注，每21天1至5天。采用国际工作组标准对答复进行中央评估。主要终点是总体应答率。次要终点包括反应持续时间(DOR)、无进展和总存活率。结果共纳入129名患者，中位数为两次系统治疗。120例可评价患者的总有效率为25.8%(31/120)，其中完全缓解13例(10.8%)，部分缓解18例(15%)。根据国际工作组的标准，中位死亡时间为13.6个月，住院时间最长的患者为36个月。中位无进展生存期为1.6个月，总生存期为7.9个月。其中12名患者在贝力诺他汀单一治疗后接受了干细胞移植。最常见的3-4级不良反应是贫血(10.8%)、血小板减少(7%)、呼吸困难(6.2%)和中性粒细胞减少(6.2%)。结论单用倍力诺他汀治疗复发性或难治性PTCL患者，无论以前的治疗次数或类型，都能产生完全和持久的反应，且毒性可控。这些结果导致美国食品和药物管理局批准贝力诺作为这一适应症。
PurposePeripheral T-cell lymphomas (PTCLs) represent a diverse group of non-Hodgkin lymphomas with a poor prognosis and no accepted standard of care for patients with relapsed or refractory disease. This study evaluated the efficacy and tolerability of belinostat, a novel histone deacetylase inhibitor, as a single agent in relapsed or refractory PTCL.Patients and MethodsPatients with confirmed PTCL who experienced progression after >= one prior therapy received belinostat 1,000 mg/m(2) as daily 30-minute infusions on days 1 to 5 every 21 days. Central assessment of response used International Working Group criteria. Primary end point was overall response rate. Secondary end points included duration of response (DoR) and progression-free and overall survival.ResultsA total of 129 patients were enrolled, with a median of two prior systemic therapies. Overall response rate in the 120 evaluable patients was 25.8% (31 of 120), including 13 complete (10.8%) and 18 partial responses (15%). Median DoR by International Working Group criteria was 13.6 months, with the longest ongoing patient at >= 36 months. Median progression-free and overall survival were 1.6 and 7.9 months, respectively. Twelve of the enrolled patients underwent stem-cell transplantation after belinostat monotherapy. The most common grade 3 to 4 adverse events were anemia (10.8%), thrombocytopenia (7%), dyspnea (6.2%), and neutropenia (6.2%).ConclusionMonotherapy with belinostat produced complete and durable responses with manageable toxicity in patients with relapsed or refractory PTCL across the major subtypes, irrespective of number or type of prior therapies. These results have led to US Food and Drug Administration approval of belinostat for this indication.