Safety of venetoclax in treatment of patients with relapsed/refractory chronic lymphoblastic leukemia: a meta-analysis
10.3760/cma.j.cn114015-20210209-00171
- VernacularTitle:维奈克拉治疗复发/难治性慢性淋巴细胞白血病安全性的meta分析
- Author:
Liang LIANG
1
;
Ting WANG
;
Ru FENG
;
Di CHEN
;
Pengfei JIN
Author Information
1. 北京医院药学部/国家老年医学中心/中国医学科学院老年医学研究院/药物临床风险与个体化应用评价北京市重点实验室，北京 100730
- Publication Type:Journal Article
- Keywords:
Genes, bcl-2;
Leukemia, lymphocytic, chronic, B-Cell;
Drug-related side effects and adverse reactions;
Meta-analysis;
Venetoclax
- From:
Adverse Drug Reactions Journal
2021;23(10):523-534
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the safety of venetoclax alone or combined with CD20 monoclonal 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 infection [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 treated with venetoclax alone (57.00% vs. 41.69%, RRR=1.36,95 %CI: 1.12-1.66; 38.18% vs. 14.97%, RRR=2.55, 95 %CI: 1.48-4.39). Conclusions:The adverse events in venetoclax treated R/R CLL were mainly hematological adverse events and the risk of grade 3-4 neutropenia was more than 40%. After the combination with CD20 mAb, the risks of the other adverse events did not increase except for those of grade 3-4 neutropenia and dose reduction of venetoclax due to adverse events.
