Nivolumab in Patients With Relapsed or Refractory Hematologic Malignancy: Preliminary Results of a Phase Ib Study
Nivolumab in Patients With Relapsed or Refractory Hematologic Malignancy: Preliminary Results of a Phase Ib Study
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DOI：
10.1200/jco.2015.65.9789
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发表时间：
2016-08-10
影响因子：
45.3
通讯作者：
Timmerman, John
中科院分区：
文献类型：
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作者：
Lesokhin, Alexander M.;Ansell, Stephen M.;Timmerman, John
目的：癌细胞可以通过调节t淋巴细胞活性，利用程序性死亡-1 （PD-1）免疫检查点途径来逃避免疫监视。在某种程度上，这可能是通过肿瘤微环境中PD-1和PD-1途径配体（PD-L1和PD-L2）的过表达而发生的。PD-1阻断剂在实体肿瘤中产生了显著的抗肿瘤活性，在血液系统恶性肿瘤中也出现了类似的证据。方法在这项开放标签、剂量递增、队列扩展的I期研究中，复发或难治性b细胞淋巴瘤、t细胞淋巴瘤和多发性骨髓瘤患者接受抗pd -1单克隆抗体nivolumab治疗，剂量为每2周1或3mg /kg。本研究旨在评估nivolumab的安全性和有效性，并评估PD-L1/PD-L2基因座完整性和蛋白表达。结果共治疗81例患者（滤泡性淋巴瘤10例，弥漫性大b细胞淋巴瘤11例，其他b细胞淋巴瘤10例，蕈样真菌病13例，外周t细胞淋巴瘤5例，其他t细胞淋巴瘤5例，多发性骨髓瘤27例）。患者之前接受过3次（范围1到12次）的系统治疗。51例（63%）患者发生药物相关不良事件，大多数为1级或2级。滤泡性淋巴瘤、弥漫性大b细胞淋巴瘤、蕈样真菌病和周围t细胞淋巴瘤患者的客观有效率分别为40%、36%、15%和40%。中位随访时间为66.6周（1.6 ~ 132.0+周）。个别患者的反应持续时间为6.0至81.6+周。结论nivolumab在广泛预处理的复发或难治性b细胞和t细胞淋巴瘤患者中具有良好的耐受性和抗肿瘤活性。纳武单抗在这些疾病中的其他研究正在进行中。(C) 2016年由美国临床肿瘤学会出版
PurposeCancer cells can exploit the programmed death-1 (PD-1) immune checkpoint pathway to avoid immune surveillance by modulating T-lymphocyte activity. In part, this may occur through overexpression of PD-1 and PD-1 pathway ligands (PD-L1 and PD-L2) in the tumor microenvironment. PD-1 blockade has produced significant antitumor activity in solid tumors, and similar evidence has emerged in hematologic malignancies.MethodsIn this phase I, open-label, dose-escalation, cohort-expansion study, patients with relapsed or refractory B-cell lymphoma, T-cell lymphoma, and multiple myeloma received the anti-PD-1 monoclonal antibody nivolumab at doses of 1 or 3 mg/kg every 2 weeks. This study aimed to evaluate the safety and efficacy of nivolumab and to assess PD-L1/PD-L2 locus integrity and protein expression.ResultsEighty-one patients were treated (follicular lymphoma, n = 10; diffuse large B-cell lymphoma, n = 11; other B-cell lymphomas, n = 10; mycosis fungoides, n = 13; peripheral T-cell lymphoma, n = 5; other T-cell lymphomas, n = 5; multiple myeloma, n = 27). Patients had received a median of three (range, one to 12) prior systemic treatments. Drug-related adverse events occurred in 51 (63%) patients, and most were grade 1 or 2. Objective response rates were 40%, 36%, 15%, and 40% among patients with follicular lymphoma, diffuse large B-cell lymphoma, mycosis fungoides, and peripheral T-cell lymphoma, respectively. Median time of follow-up observation was 66.6 weeks (range, 1.6 to 132.0+ weeks). Durations of response in individual patients ranged from 6.0 to 81.6+ weeks.ConclusionNivolumab was well tolerated and exhibited antitumor activity in extensively pretreated patients with relapsed or refractory B-and T-cell lymphomas. Additional studies of nivolumab in these diseases are ongoing. (C) 2016 by American Society of Clinical Oncology