Safety and activity of sintilimab in patients with relapsed or refractory classical Hodgkin lymphoma (ORIENT-1): a multicentre, single-arm, phase 2 trial
Safety and activity of sintilimab in patients with relapsed or refractory classical Hodgkin lymphoma (ORIENT-1): a multicentre, single-arm, phase 2 trial
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DOI：
10.1016/s2352-3026(18)30192-3
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发表时间：
2019-01-01
影响因子：
24.7
通讯作者：
Liu, Peng
中科院分区：
文献类型：
--
作者：
Shi, Yuankai;Su, Hang;Liu, Peng
背景Sintiliumab（Innovent Biologics，中国苏州）是一种高选择性、完全人源化的单克隆抗体，可阻断PD-1与其配体之间的相互作用。我们的目的是评估信替利单抗在中国复发或难治性经典型霍奇金淋巴瘤患者中的活性和安全性，方法在这项正在进行的单臂2期研究中，我们从中国18家医院招募了经组织病理学诊断的经典型霍奇金淋巴瘤患者，这些患者在接受两种或多种治疗后复发或难治。患者静脉注射sintiliumab（200 mg，每3周一次），直至疾病进展、死亡、不可接受的毒性或撤回知情同意。主要结局是全分析集中（即，经中心病理学实验室证实的典型霍奇金淋巴瘤患者）在最后一例患者入组后24周时由独立放射学审查委员会（IRRC）评估为客观缓解的患者比例。在基线、第6、15和24周、第24 - 48周每12周一次以及第48周后每16周一次通过增强CT扫描或MRI评估肿瘤缓解。在2017年4月19日至2017年11月1日期间，共有96名患者入组并开始治疗。从全分析集中排除了4例患者，其诊断随后未得到中心病理学实验室证实。10名患者停止治疗。中位随访时间为10.5个月。在全分析集（n=92）中，74例患者（80.4%; 95% CI 70.9-88.0）在分析截止日期2018年4月16日之前达到IRRC评估的客观缓解。96例患者中有89例（93%）发生治疗相关不良事件，17例患者（18%）发生3级或4级治疗相关不良事件，最常见的是发热（3例[3%]患者）。14例（15%）患者发生任何原因的严重不良事件。研究期间无患者死亡。解读信替利单抗可能成为中国复发或难治性经典型霍奇金淋巴瘤患者的新治疗选择。版权所有（C）2019 Elsevier Ltd.保留所有权利。
Background Sintilimab (Innovent Biologics, Suzhou, China), a highly selective, fully humanised, monoclonal antibody, blocks the interaction between PD-1 and its ligands. We aimed to assess the activity and safety profile of sintilimab in Chinese patients with relapsed or refractory classical Hodgkin lymphoma.Pviethods In this ongoing, single-arm, phase 2 study, we recruited patients with histopathologically diagnosed classical Hodgkin lymphoma that was relapsed or refractory after two or more lines of therapy from 18 hospitals in China. Patients were given intravenous sintilimab (200 mg, once every 3 weeks) until progression, death, unacceptable toxicity, or withdrawal of consent. The primary outcome was the proportion of patients in the full analysis set (ie, those with classical Hodgkin lymphoma confirmed by the central pathology laboratory) who had an objective response, as assessed by an independent radiological review committee (IRRC), by 24 weeks after enrolment of the last patient. Tumour response was assessed by enhanced CT scan or MRI at baseline, at weeks 6, 15, and 24, every 12 weeks from weeks 24 to 48, and every 16 weeks beyond week 48. Safety was assessed in all treated patients.Findings Between April 19, 2017, and Nov 1, 2017, 96 patients were enrolled and commenced treatment. Four patients, whose diagnosis was not subsequently confirmed by the central pathology laboratory, were excluded from the full analysis set. Ten patients discontinued treatment. Median duration of follow-up was 10.5 months. In the full analysis set (n=92), 74 patients (80.4%; 95% CI 70.9-88.0) had an IRRC-assessed objective response before the analysis cutoff date of April 16, 2018. 89 (93%) of 96 patients had treatment-related adverse events, and 17 patients (18%) had grade 3 or 4 treatment-related adverse events, the most common being pyrexia (three [3%] patients). 14 (15%) patients had serious adverse events of any cause. No patient died during the study.Interpretation Sintilimab could be a new treatment option for patients with relapsed or refractory classical Hodgkin lymphoma in China. Copyright (C) 2019 Elsevier Ltd. All rights reserved.