不同酪氨酸激酶抑制剂治疗慢性髓系白血病有效性和安全性的网状Meta分析

Efficacy and safety of flumatinib for chronic myelocytic leukemia:a network meta-analysis

目的系统评价不同酪氨酸激酶抑制剂(TKIs)治疗慢性髓系白血病(CML)的有效性和安全性。方法计算机检索PubMed、EMbase、The Cochrane Library、CNKI、WanFang Data和CBM数据库,搜集氟马替尼、尼洛替尼、达沙替尼和伊马替尼治疗CML的随机对照试验(RCT),检索时限均从建库至2020年8月。由2名研究者独立筛选文献、提取资料并评价纳入研究的偏倚风险后,采用Stata 15.0软件和R 3.4.0软件进行网状Meta分析。结果最终纳入8个RCT,包括2775例患者。与其他TKIs相比,氟马替尼3个月早期分子学反应(EMR)和1年无进展生存期(PFS)更高,严重不良反应发生率更低。其主要分子学反应(MMR)和完全细胞遗传学反应(CCyR)明显优于伊马替尼,与其他二代TKIs具有同等或近似效果。结论当前证据显示,氟马替尼治疗CML优于伊马替尼,与其他二代TKIs具有同等或近似效果。受纳入研究数量和质量的限制,上述结论尚待更多高质量研究予以验证。

Objective To systematically review the efficacy and safety of different tyrosine kinase inhibitors(TKIs)in the treatment of chronic myelocytic leukemia(CML).Methods PubMed,EMbase,The Cochrane Library,CBM,WanFang Data and CNKI databases were electronically searched to collect randomized controlled trials(RCTs)of nilotinib,dasatinib,flumatinib and imatinib for CML from inception to August,2020.Two reviewers independently screened literature,extracted data and assessed the risk of bias of included studies;network meta-analysis was then performed using Stata 15.0 software and R 3.4.0 software.Results A total of 8 RCTs involving 2775 patients were included.Compared with other TKIs,flumatinib had higher 3-month early molecular response and 1-year progression free survival,and the incidence of serious side effects was relatively low.Major molecular response and complete cytogenetic response were significantly superior to imatinib,and had the same or similar effects to other secondgeneration TKIs.Conclusions Current evidence shows that flumartinib in the treatment of CML is obviously superior to imatinib,has the same or similar effect with other second generation TKIs.Due to limited quality and quantity of the included studies,more high quality studies are needed to verify above conclusions.