尼洛替尼/达沙替尼对比伊马替尼治疗初诊慢性期慢性髓系白血病的Meta分析

Nilotinib/dasatinib compared with imatinib in treatment of newly diagnosed chronic-phase chronic myeloid leukemia: a meta-analysis

目的系统评价尼洛替尼/达沙替尼对比伊马替尼治疗初诊慢性期慢性髓系白血病(CML)的疗效和血液学安全性。方法计算机检索Cochrane图书馆、Pub Med、中国期刊全文数据库、万方数据库等,纳入尼罗尼替/达沙替尼(试验组)对比伊马替尼(对照组)治疗慢性期CML的随机对照试验(RCT)。提取资料并交叉核对,对纳入的研究进行质量评价,采用Rev Man 5.2统计学软件进行Meta分析。结果共纳入8项RCT,合计1 375例患者。Meta分析结果显示,与对照组相比,试验组3年累计主要分子学反应(MMR)增高[RR=1.31,95%CI(1.20,1.44),P<0.000 01]、3年累计MR4增高[RR=2.27,95%CI(1.78,2.90),P<0.000 01],3年累计MR4.5增高[RR=2.0,95%CI(1.58,2.53),P<0.000 01];2年、1年、9个月、6个月、3个月累计MMR,2年累计MR4.5,2年和1年累计完全细胞遗传学反应(CCy R)均增高。而3年总体生存(OS)率[RR=1.01,95%CI(0.99,1.04),P=0.18]、3年无进展生存(PFS)率[RR=1.35,95%CI(0.89,2.04),P=0.16]组间比较无显著差异。试验组3~4级血小板减少发生率高于对照组[RR=1.59,95%CI(1.20,2.12),P=0.001],但不良反应相关的治疗终止发生率[RR=1.23,95%CI(0.88,1.70),P=0.22]不增加。结论尼洛替尼/达沙替尼作为慢性期CML治疗的首选可能获益更多,但还需要更多高质量RCT、更长期的随访进一步验证。

comparing with so as to provide AIM To systematically evaluate the efficacy and hematological safety of nilotinib/dasatinib, imatinib in the treatment of newly diagnosed chronic-phase chronic myeloid leukemia （CML）, evidence for clinical treatment. METHODS The random controlled trials （RCT） of comparing imatinib （control group） with nilotinib/dasatinib （experimental group） in treating chronicphase CML were retrieved from Cochrane library, PubMed, Chinese Journal Full-text Database （CJFD）, Wanfang data and so on by computer. After data extraction and cross-reference, the quality of included studies were evaluated, and meta-analysis of included studies were performed by Rev Man 5.2 software. RESULTS A total of eight RCT, including 1 375 patients, were included. The results of meta-analysis indicated that, compared with the control group, three-years accumulated major molecular response （MMR, RR = 1.31, 95%CI （1.20, 1.44）, P 〈 0.000 01） of the experimental group increased; three-years accumulated MR4 （RR = 2.27, 95%CI （1.78, 2.90）, P 〈 0.000 01） and three-years accumulated MR45 （RR = 2.0, 95%CI （1.58, 2.53）, P 〈 0.000 01） of the experimental group also increased. Besides, accumulated MMR of two years, one year, nine months, six months and three months all increased; accumulated MR45 of two years and accumulated complete cytogenetic response （CCyR） of two years and one year increased, too. While three-years overall survival （OS, RR = 1.01, 95%CI （0.99, 1.04）, P= 0.18） and progress free survival （PFS, RR = 1.35, 95%CI （0.89, 2.04）, P =0.16） showed no significant difference between two groups. The incidence of grade 3 to grade 4 thrombocytopenia （RR = 1.59, 95%CI （1.20, 2.12）, P = 0.001） was significantly increased in the experimental group compared with that in the control group. However, there were no significant differences in the incidence of~ adverse reactions related discontinued treatment （RR = 1.23, 95%CI （0.88, 1.70）, P = 0.22）. CONCLUSION Nilotinib/dasatinib as the first line therapeutics for the treatment of chronicphase CML might be advantageous over the first-generation tyrosine kinase inhibitors, but more high quality RCT with prolonged follow-up period are required for further validation of the conclusion.