Panobinostat in Patients With Relapsed/Refractory Hodgkin's Lymphoma After Autologous Stem-Cell Transplantation: Results of a Phase II Study
Panobinostat in Patients With Relapsed/Refractory Hodgkin's Lymphoma After Autologous Stem-Cell Transplantation: Results of a Phase II Study
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DOI：
10.1200/jco.2011.38.1350
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发表时间：
2012-06-20
影响因子：
45.3
通讯作者：
Engert, Andreas
中科院分区：
文献类型：
--
作者：
Younes, Anas;Sureda, Anna;Engert, Andreas
目的霍奇金淋巴瘤(HL)对自体干细胞移植(ASCT)复发或难治的患者没有标准的治疗方法。这项第二阶段的研究考察了帕诺比坦在该人群中的安全性和活性。患者和方法帕诺比坦40 mg，每周口服三次。主要终点是基于研究人员的放射成像评估的客观反应率(ORR)。次要终点包括独立中心评审的ORR、反应时间(TTR)、反应持续时间(DOR)、无进展生存期(PFS)、总生存期和安全性。结果129名接受治疗的患者(年龄中位数为32岁，年龄范围为18至75岁)在接受系统治疗前平均接受了4次(范围为2至7次)的大量预治疗，41%的患者对紧接在帕诺比妥之前的治疗方案没有反应。96名患者(74%)肿瘤缩小。客观缓解35例(27%)，其中部分缓解30例(23%)，完全缓解5例(4%)。中位TTR为2.3个月，中位DOR为6.9个月，中位PFS为6.1个月。估计1年总存活率为78%。常见的非血液学不良反应(AEs)--腹泻、恶心、呕吐和疲劳--通常为1级和2级。大多数常见的3级和4级血液学不良反应(AEs)--血小板减少、贫血和中性粒细胞减少--是可控的。在获得完全或部分应答的患者中，观察到早期胸腺和激活调节趋化因子的减少。结论在对复发或对ASCT无效的严重预治疗的HL患者进行的最大规模、前瞻性、多中心的国际试验中，Panobinostat单一治疗显示出抗肿瘤活性，导致持久的反应。J Clin Oncol30：2197-2203。(C)2012年美国临床肿瘤学会
PurposeHodgkin's lymphoma (HL) has no standard of care for patients who are relapsed or refractory to autologous stem-cell transplantation (ASCT). This phase II study examined safety and activity of panobinostat in this population.Patients and MethodsPanobinostat 40 mg was administered orally three times per week. The primary end point was objective response rate (ORR) based on investigator assessment of radiologic imaging. Secondary end points included ORR by independent central review, time to response (TTR), duration of response (DOR), progression-free survival (PFS), overall survival, and safety. Exploratory biomarker analyses were performed.ResultsThe 129 treated patients (median age, 32 years; range, 18 to 75 years) were heavily pretreated with a median of four (range, two to seven) prior systemic regimens, and 41% did not respond to the regimen immediately preceding panobinostat. Tumor reductions occurred in 96 patients (74%). Objective response was achieved by 35 patients (27%), including 30 (23%) partial responses and five (4%) complete responses. The median TTR was 2.3 months, median DOR was 6.9 months, and median PFS was 6.1 months. The estimated 1-year overall survival rate was 78%. Common nonhematologic adverse events (AEs)-diarrhea, nausea, vomiting, and fatigue-were generally grade 1 and 2. Most common grade 3 and 4 hematologic AEs-thrombocytopenia, anemia, and neutropenia-were manageable. Early reductions in thymus and activation-regulated chemokine were observed in patients achieving complete or partial response.ConclusionIn the largest, prospective, multicenter, international trial conducted in heavily pretreated patients with HL who relapsed or were refractory to ASCT, panobinostat monotherapy demonstrated antitumor activity, resulting in durable responses. J Clin Oncol 30:2197-2203. (c) 2012 by American Society of Clinical Oncology