摘要
目的评价维奈克拉单药或联合CD20单克隆抗体(单抗)治疗复发/难治性慢性淋巴细胞白血病(R/R CLL)的安全性。方法检索PubMed、Embase、中国知网、万方医学、维普网、中国生物医学文献数据库以及ClinicalTrials.gov、美国食品药品监理局和欧洲药品管理局等网站,收集结局指标包含安全性的维奈克拉单药或联合CD20单抗治疗R/R CLL的临床研究,提取安全性相关数据,采用R软件进行meta分析,效应量为相对风险比(RRR)及其95%置信区间(CI)。结果共纳入9项研究,全部为单臂临床研究(前瞻性研究8项,回顾性研究1项),共纳入819例患者,其中单药组719例,联合用药组100例。维奈克拉单药或联合CD20单抗最常见的不良事件为血液系统不良事件,3~4级中性粒细胞缺乏、血小板减少和贫血发生的风险分别为46.96%(95%CI:40.27%~53.76%)、20.46%(95%CI:14.79%~27.59%)和15.31%(95%CI:10.30%~22.15%)。其他3~4级不良事件主要包括感染[17.79%(95%CI:15.15%~20.77%)]、肿瘤溶解综合征[3.00%(95%CI:1.75%~5.09%)]、高血糖[5.98%(95%CI:3.80%~9.29%)]和低钾血症[4.27%(95%CI:2.54%~7.08%)]。因为不良事件,28.82%(95%CI:16.56%~45.24%)的患者中断维奈克拉治疗≥1次,17.19%(95%CI:10.96%~25.94%)的患者降低维奈克拉剂量,9.56%(95%CI:7.64%~11.89%)的患者永久停用维奈克拉,1.90%(95%CI:0.86%~4.17%)的患者死亡。接受维奈克拉联合CD20单抗治疗的患者3~4级中性粒细胞减少发生风险和维奈克拉减量风险明显高于单用维奈克拉患者(57.00%比41.69%,RRR=1.36,95%CI:1.12~1.66;38.18%比14.97%,RRR=2.55,95%CI:1.48~4.39)。结论维奈克拉治疗R/R CLL的不良事件主要为血液系统不良事件,3~4级中性粒细胞减少发生风险超过40%。联用CD20单抗后,除3~4级中性粒细胞减少和因不良事件导致维奈克拉减量的风险明显增加外,其他不良事件发生风险并未增加。
Objective To evaluate the safety of venetoclax alone or combined with CD20 mono‑clonal antibody(mAb)in treatment of patients with relapsed/refractory chronic lymphoblastic leukemia(R/R CLL).Methods Databases of PubMed,Embase,CNKI,Wanfang Med Online,VIP,and SinoMed and websites such as ClinicalTrials.gov,the U.S.Food and Drug Administration(FDA),and the European Drug Administration(EMA)were searched.The clinical studies with safety indicators of venetoclax alone or in combination with CD20 mAb in treatment of patients with R/R CLL were collected.Safety‑relevant data were extracted and the meta‑analysis was performed using R software.The effect values were the ratio of relative risk(RRR)and 95%confidence interval(CI).Results A total of 9 studies were enrolled in the analysis,all of which were single arm studies(8 prospective studies and 1 retrospective study).Eight hundred and nineteen patients were involved in the 9 studies,719 of which were in the monotherapy group and 100 in the 2‑drug combination group.The most common adverse events in venetoclax monotherapy or combined with CD20 mAb were hematologic adverse events.The risk of developing grade 3‑4 neutrophilia,thrombocytopenia,and anemia was 46.96%(95%CI:40.27%‑53.76%),20.46%(95%CI:14.79%‑27.59%),and 15.31%(95%CI:10.30%‑22.15%),respectively.Other grade 3‑4 adverse events mainly included infec‑tion[17.79%(95%CI:15.15%‑20.77%)],tumor lysis syndrome[3.00%(95%CI:1.75%‑5.09%)],increased blood glucose[5.98%(95%CI:3.80%‑9.29%)],and hypokalemia[4.27%(95%CI:2.54%‑7.08%)].Due to the adverse events,28.82%(95%CI:16.56%‑45.24%)of patients interrupted venetoclax treatment for at least one dose,17.19%(95%CI:10.96%‑25.94%)of patients reduced the venetoclax dose,9.56%(95%CI:7.64%‑11.89%)of patients permanently discontinued venetoclax,and 1.90%(95%CI:0.86%‑4.17%)of patients died.Risks of grade 3‑4 neutropenia and dose reduction of venetoclax were significantly higher in patients treated with venetoclax combined with CD20 mAb than in those tr
作者
梁良
王婷
冯茹
陈頔
金鹏飞
Liang Liang;Wang Ting;Feng Ru;Chen Di;Jin Pengfei(Department of Pharmacy,Beijing Hospital,National Center of Gerontology,Institute of Geriatric Medicine,Chinese Academy of Medical Science,Beijing Key Laboratory of Assessment for Clinical Risk and Individual Application of Drugs,Beijing 100730,China;Department of Hematology,Beijing Hospital,National Center of Gerontology,Institute of Geriatric Medicine,Chinese Academy of Medical Science,Beijing 100730,China)
出处
《药物不良反应杂志》
CSCD
2021年第10期523-534,共12页
Adverse Drug Reactions Journal
