博纳吐单抗治疗复发/难治性B细胞急性淋巴细胞白血病患儿的疗效和安全性：一项系统评价和荟萃分析

Efficacy and safety of blinatumomab in children with relapsed/refractory B cell acute lymphoblastic leukemia: A systematic review and meta-analysis.

作者信息

Chen Bin, Zou Zhuan, Zhang Qian, Chen Kexing, Zhang Xiaoyan, Xiao Dongqiong, Li Xihong

机构信息

Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China.

Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Chengdu, China.

出版信息

Front Pharmacol. 2023 Jan 10;13:1032664. doi: 10.3389/fphar.2022.1032664. eCollection 2022.

DOI:10.3389/fphar.2022.1032664

PMID:36703737

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9871389/

Abstract

Several clinical trials have been conducted to evaluate the effects of blinatumomab in childhood B cell acute lymphoblastic leukemia (B-ALL). We conducted this meta-analysis to validate the efficacy and safety of blinatumomab in pediatric patients with relapsed/refractory B-ALL (R/R B-ALL). We searched and investigated all relevant studies in the PubMed, Web of Science, Embase, and Cochrane Library databases. The primary outcomes were complete response (CR), overall survival (OS), event free survival (EFS), minimal residual disease (MRD) response, allogeneic hematopoietic stem cell transplantation (allo-HSCT) and were calculated separately for randomized controlled trials (RCTs) and single-arm studies. The secondary end points were adverse effects (AEs) and the relapse rate. The Cochrane, bias assessment tool, was used to assess the risk of bias in RCTs. The methodological quality of single-arm studies was assessed using the methodological index for non-randomized studies (MINORS) tool. The meta-analysis included two RCTs and 10 single-arm studies, including 652 patients in total. Our study showed that in the single-arm studies, the combined CR rate was 0.56 (95% confidence interval (CI): 0.45 -0.68), the odds ratios (ORs) of OS was 0.43 (95% CI 0.32 -0.54), the EFS rate was 0.30 (95% CI: 0.20 -0.40), the MRD response was 0.51 (95% CI: 0.34 -0.68), allo-HSCT rate was 0.62 (95% CI: 0.50 -.74), the AE rate was 0.65 (95% CI: 0.54 -0.76) and the relapse rate was 0.32 (95% CI: 0.27 -0.38). In the RCTs, the blinatumomab-treated group compared with the chemotherapy group had a combined OS rate of 0.12 (95% CI: 0.05 -0.19) and an EFS rate of 2.16 (95% CI: 1.54 -3.03). The pooled MRD response rate was 4.71 (95% CI:2.84 -7.81), allo-HSCT was 3.24 (95% CI: 1.96 -5.35), the AE rate was 0.31 (95% CI: 0.16 -0.60), and the relapse rate was 0 .69 (95% CI: 0.43 -1.09). According to this meta-analysis, blinatumomab shows potent therapeutic efficacy and limited AEs in children with R/R B- ALL. https://www.crd.york.ac.uk/prospero/, identifier CRD42022361914.

摘要

已经开展了多项临床试验来评估博纳吐单抗治疗儿童B细胞急性淋巴细胞白血病（B-ALL）的效果。我们进行了这项荟萃分析，以验证博纳吐单抗在复发/难治性B-ALL（R/R B-ALL）儿科患者中的疗效和安全性。我们检索并研究了PubMed、科学网、Embase和考克兰图书馆数据库中的所有相关研究。主要结局为完全缓解（CR）、总生存期（OS）、无事件生存期（EFS）、微小残留病（MRD）缓解情况、异基因造血干细胞移植（allo-HSCT），并分别针对随机对照试验（RCT）和单臂研究进行计算。次要终点为不良反应（AE）和复发率。采用考克兰偏倚评估工具来评估RCT中的偏倚风险。使用非随机研究方法学指数（MINORS）工具评估单臂研究的方法学质量。该荟萃分析纳入了2项RCT和10项单臂研究，共652例患者。我们的研究表明，在单臂研究中，合并CR率为0.56（95%置信区间（CI）：0.45 -0.68），OS的优势比（OR）为0.43（95%CI 0.32 -0.54），EFS率为0.30（95%CI：0.20 -0.40），MRD缓解率为0.51（95%CI：0.34 -0.68），allo-HSCT率为0.62（95%CI：0.50 -.74），AE率为0.65（95%CI：0.54 -0.76），复发率为0.32（95%CI：0.27 -0.38）。在RCT中，与化疗组相比，博纳吐单抗治疗组的合并OS率为0.12（95%CI：0.05 -0.19），EFS率为2.16（95%CI：1.54 -3.03）。汇总的MRD缓解率为4.71（95%CI：2.84 -7.81），allo-HSCT为3.24（95%CI：1.96 -5.35），AE率为0.31（95%CI：0.16 -0.60），复发率为0.69（95%CI：0.43 -1.09）。根据这项荟萃分析，博纳吐单抗在R/R B-ALL儿童患者中显示出强大的治疗效果且不良反应有限。https://www.crd.york.ac.uk/prospero/，标识符CRD42022361914