Venetoclax plus obinutuzumab versus chlorambucil plus obinutuzumab for previously untreated chronic lymphocytic leukaemia (CLL14): follow-up results from a multicentre, open-label, randomised, phase 3 trial
Venetoclax plus obinutuzumab versus chlorambucil plus obinutuzumab for previously untreated chronic lymphocytic leukaemia (CLL14): follow-up results from a multicentre, open-label, randomised, phase 3 trial
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DOI：
10.1016/s1470-2045(20)30443-5
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发表时间：
2020-09-01
期刊：
影响因子：
51.1
通讯作者：
Fischer, Kirsten
中科院分区：
文献类型：
--
作者：
Al-Sawaf, Othman;Zhang, Can;Fischer, Kirsten
背景：万乃克拉司联合奥比诺单抗已被确定为慢性淋巴细胞白血病患者的固定疗程治疗方案。我们比较了未经治疗的慢性淋巴细胞性白血病患者停用万乃馨联合obinutuzumab治疗后的长期疗效。方法CLL14是一项多中心、随机、开放的3期试验，在21个国家和地区的196个地点进行。符合条件的患者年龄为18岁或以上，有未经治疗的慢性淋巴细胞白血病，以及合并疾病的累积病情分级大于6，肌酐清除量30-69毫升/分钟，或两者兼有。患者通过网络和语音信箱系统随机分配(1：1)，分配隐藏，基于计算机生成的随机时间表，区组大小为6，并按比奈分期和地理区域分层。患者在第1周期的第22天[28天周期]开始服用文奈德+奥比诺单抗，5周剂量递增[20 mg，50 mg，100 mg，200 mg，然后每天400 mg，持续1周]，此后继续每天400 mg，直到第12周期结束；联合用药：第1天100 mg，第2天900 mg，第1天1000 mg，第1周期第15天1000 mg，第2~6周期第1天1000 mg，第2~6周期第1天1000 mg；主要终点是研究者评估的意向治疗人群中的无进展存活率。对所有接受了至少一剂研究治疗的患者进行了安全性评估。患者登记完成，这项研究已在ClinicalTrails.gov，NCT02242942注册。2015年8月7日至2016年8月4日，432名患者登记并随机分配接受ventoclax加obinutuzumab(n=216)或氯氨丁尼+obinutuzumab(n=216)。在数据收集时，所有患者都已停止治疗至少24个月。在39.6个月的中位随访期(IQR 36.8-43.0)中，接受文奈德联合obinutuzumab的患者的无进展生存期显著长于接受氯氨丁苯联合obinutuzumab的患者(HR 0.31，95%CI 0.22-0.44；p
Background Venetoclax plus obinutuzumab has been established as a fixed-duration treatment regimen for patients with chronic lymphocytic leukaemia. We compared the long-term efficacy after treatment cessation of the combination of venetoclax plus obinutuzumab with chlorambucil plus obinutuzumab in patients with previously untreated chronic lymphocytic leukaemia.Methods CLL14 is a multicentre, randomised, open-label, phase 3 trial done at 196 sites in 21 countries. Eligible patients were aged 18 years or older, had untreated chronic lymphocytic leukaemia, and coexisting conditions with a cumulative illness rating scale greater than 6, a creatinine clearance of 30-69 mL/min, or both. Patients were randomly assigned (1:1) via a web and voicemail system with allocation concealment and based on a computer generated randomisation schedule with a block size of six and stratified by Binet stage and geographical region. Patients received either venetoclax plus obinutuzumab (oral venetoclax initiated on day 22 of cycle 1 [28-day cycles], with a 5-week dose ramp-up [20 mg, 50 mg, 100 mg, and 200 mg, then 400 mg daily for 1 week], thereafter continuing at 400 mg daily until completion of cycle 12; combined with intravenous obinutuzumab for six cycles starting with 100 mg on day 1 and 900 mg on day 2 [or 1000 mg on day 1], 1000 mg on days 8 and day 15 of cycle 1, and subsequently 1000 mg on day 1 of cycles 2 through 6) or chlorambucil plus obinutuzumab (oral chlorambucil at 0.5 mg/kg bodyweight on days 1 and 15 of each cycle for 12 cycles combined with the same obinutuzumab regimen). The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. Patient enrolment is complete, and the study is registered with ClinicalTrails.gov, NCT02242942.Findings Between Aug 7, 2015, and Aug 4, 2016, 432 patients were enrolled and randomly assigned to receive either venetoclax plus obinutuzumab (n=216) or chlorambucil plus obinutuzumab (n=216). All patients had been off treatment for at least 24 months at data collection. At a median follow-up of 39.6 months (IQR 36.8-43.0), patients given venetoclax plus obinutuzumab had a significantly longer progression-free survival than did patients given chlorambucil plus obinutuzumab (HR 0.31, 95% CI 0.22-0.44; p