免疫调节药物治疗多发性骨髓瘤发生深静脉血栓风险的系统评价和Meta分析

目的:系统评价免疫调节药物(IMiDs)治疗多发性骨髓瘤(MM)发生深静脉血栓(DVT)的风险,为临床安全用药提供参考。方法:计算机检索自建库起至2018年12月31日PubMed、Web of Science、Cochrane图书馆、中国期刊全文数据库、万方数据、中文科技期刊数据库、www.ClinicalTrials.gov中有关IMiDs治疗MM患者发生DVT风险的随机对照试验(RCT)。使用Stata 12.0统计软件对DVT发生率和相对危险度(RR)进行Meta分析,使用GRADE系统对所得证据进行评估分级。结果:共纳入11项RCT,合计3 365例患者(其涉及3种药)。Meta分析结果显示,使用IMiDs治疗MM时DVT的发生率为7.3%[95%CI(4.5%,10.2%)]。与常规化疗相比,IMiDs治疗MM发生DVT的风险更高[RR=3.57,95%CI(2.42,5.27),P<0.01]。不同治疗阶段的亚组分析显示,IMiDs治疗诱导阶段MM患者后,DVT发生的风险较常规化疗方案增加386%[RR=4.86,95%CI(2.85,8.30),P<0.01],该证据级别为中等;与常规化疗方案相比,IMiDs在维持阶段[RR=2.40,95%CI(0.70,8.27),P=0.16]和复发阶段[RR=2.01,95%CI(0.74,5.46),P=0.17]治疗MM患者DVT发生风险无显著性差异。沙利度胺、来那度胺致DVT发生率分别为11%[95%CI(9%,13%)]、3%[95%CI(2%,4%)]。结论:现有证据表明,IMiDs在MM治疗发生DVT的风险较高,临床用药需关注。

Risk of Immunomodulatory Drugs in the Treatment of Deep Venous Thrombosis in Multiple Myeloma:Systematic Evaluation and Meta-analysis

OBJECTIVE:To evaluate immunomodulatory drugs(IMiDs)in the treatment of deep venous thrombosis(DVT)in patients with multiple myeloma(MM)systematically,and to provide reference for safe drug use in clinic. METHODS:Retrieved and collected randomized controlled trials(RCTs)about the risk of DVT in MM patients treated with IMiDs from PubMed,Web of Science,Cochrane library,CJFD,Wanfang database,VIP,www.Clinical Trials.gov during database and Dec. 31,2018. Metaanalysis was conducted for the incidence and relative risk of DVT(RR) by using Stata 12.0 statistical software. Evidence was evaluated and graded by using GRADE system. RESULTS:A total of 11 RCTs were included,involving 3 365 patients(including3 drugs). Results of Meta-analysis showed that the incidence of DVT was 7.3%[95%CI(4.5%,10.2%)] during IMi Ds in the treatment of MM. Compared with conventional chemotherapy,IMi Ds had a higher risk of DVT in MM patients [RR=3.57,95%CI(2.42,5.27),P<0.01]. Subgroup analysis in different treatment stage showed that after IMi Ds treatment for MM patients at induction stage,the risk of DVT increased by 386% compared with conventional chemotherapy plan [RR=4.86,95% CI(2.85,8.30),P<0.01],which evidence was moderate. Compared with conventional chemotherapy plan,there was no significant difference in the risk of DVT among MM patients treated with IMi Ds at maintenance stage [RR=2.40,95%CI(0.70,8.27),P=0.16] and relapse stage [RR=2.01,95% CI(0.74,5.46),P=0.17]. The incidence of severe DVT caused by thalidomide and lenalidomide were 11%[95% CI(9%,13%)] and 3%[95% CI(2%,4%)]. CONCLUSIONS:The current evidence suggests that patients with MM treated with IMiDs are at a high risk of serious DVT,and clinical medication should be cautious.