Wang Jinjin, Zhao Ailin, Zhou Hui, Zhu Jinbing, Niu Ting
Department of Hematology, Institute of Hematology, West China Hospital, Sichuan University, Chengdu, China.
Front Pharmacol. 2020 Nov 20;11:580622. doi: 10.3389/fphar.2020.580622. eCollection 2020.
Ibrutinib is an oral covalent Bruton's tyrosine kinase inhibitor that has been approved for chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia and some other B-cell malignancies. Some studies have found an increased risk of bleeding with ibrutinib. Some studies, however, found no significant differences in the risk of major bleeding between patients treated with ibrutinib and those with other regimens. So, a systematic review and meta-analysis of randomized controlled trials (RCTs) were performed to estimate the risk of bleeding associated with ibrutinib in patients with B-cell malignancies. A systematic search of PUBMED, EMBASE, Central Register of Controlled Trials, and ClinicalTrials.gov was conducted from January 2000 to February 2020 to identify RCTs by comparing ibrutinib with other agents or placebo in B-cell malignancies. The RevMan software (version 5.3) was used to carry out this analysis, and the analyzed data were represented by risk ratios (RR) and 95% confidence intervals (CI). There were 11 eligible RCTs (4,288 patients). All studies reported major bleeding, and seven studies reported overall bleeding (any-grade bleeding). Ibrutinib was associated with a significantly increased risk of bleeding (overall bleeding and major bleeding) in patients with B-cell malignancies [RR = 2.56, 95% CI 1.68-3.90, < 0.0001 and RR = 2.08, 95% CI 1.36-3.16, = 0.0006, respectively]. The bleeding (overall bleeding and major bleeding) risk in patients with CLL was more obvious [RR = 3.08, 95% CI 2.07-4.58, < 0.00001 and RR = 2.46, 95% CI 1.37-4.41, = 0.003, respectively]. There were no statistically significant differences for risk of bleeding between the subgroups based on dose and treatment setting. Ibrutinib was associated with a significantly higher risk of bleeding (both overall bleeding and major bleeding) in patients with B-cell malignancies, especially in CLL.
伊布替尼是一种口服共价布鲁顿酪氨酸激酶抑制剂，已被批准用于治疗慢性淋巴细胞白血病（CLL）/小淋巴细胞白血病以及其他一些B细胞恶性肿瘤。一些研究发现使用伊布替尼会增加出血风险。然而，另一些研究发现接受伊布替尼治疗的患者与接受其他治疗方案的患者相比，大出血风险并无显著差异。因此，进行了一项随机对照试验（RCT）的系统评价和荟萃分析，以评估B细胞恶性肿瘤患者使用伊布替尼相关的出血风险。2000年1月至2020年2月期间，对PUBMED、EMBASE、对照试验中央注册库和ClinicalTrials.gov进行了系统检索，以确定在B细胞恶性肿瘤中将伊布替尼与其他药物或安慰剂进行比较的随机对照试验。使用RevMan软件（5.3版）进行该分析，分析数据以风险比（RR）和95%置信区间（CI）表示。有11项符合条件的随机对照试验（4288例患者）。所有研究均报告了大出血情况，7项研究报告了总体出血情况（任何级别的出血）。伊布替尼与B细胞恶性肿瘤患者出血风险显著增加相关（总体出血和大出血）[RR = 2.56，95%CI 1.68 - 3.90，<0.0001；RR = 2.08，95%CI 1.36 - 3.16，= 0.0006]。CLL患者的出血（总体出血和大出血）风险更为明显[RR = 3.08，95%CI 2.07 - 4.58，<0.00001；RR = 2.46，95%CI 1.37 - 4.41，= 0.003]。基于剂量和治疗背景的亚组之间出血风险无统计学显著差异。伊布替尼与B细胞恶性肿瘤患者出血风险显著更高相关（总体出血和大出血均如此），尤其是在CLL患者中。
