沙利度胺一线治疗策略对骨髓瘤患者复发后生存率影响的Meta分析

Effect of Thalidomide as First-line Therapy on Postrelapse Survival Rate of Multiple Myeloma:A Meta-analysis

目的系统评价一线应用沙利度胺对骨髓瘤患者复发后生存率的影响。方法计算机检索Pub Med、EMbase、The Cochrane Library(2007年第1期)和Web of Science数据库,搜集沙利度胺一线治疗多发性骨髓瘤的相关随机对照试验(RCT),检索时限从2006年至2011年。由2位评价员独立筛选文献、提取资料并评价纳入研究的偏倚风险后,采用Rev Man 5.1软件进行Meta分析。结果共纳入16个RCT,包括6 097例患者。Meta分析结果显示:早期应用沙利度胺组患者复发后1年生存率明显低于常规化疗组,且差异有统计学意义[HR=1.25,95%CI(1.09,1.42),P=0.001]。进一步的亚组分析结果显示:与常规化疗组相比,移植后应用沙利度胺维持治疗对复发后生存率无影响[HR=0.90,95%CI(0.57,1.41),P=0.64],移植前应用沙利度胺诱导治疗[HR=1.21,95%CI(1.01,1.45),P=0.04]及移植前诱导治疗+移植后维持治疗[HR=1.41,95%CI(1.13,1.76),P=0.002]会降低患者复发后生存率,且差异有统计学意义。结论目前临床证据表明,移植后应用沙利度胺维持治疗策略为一种较佳的治疗方案,患者复发后生存率未见明显降低,无病生存率及总生存率明显提高。受纳入研究数量和质量的限制,上述结论尚需开展更多高质量研究予以验证。

Objective To systematically review the effect of thalidomide as first-line therapy on postrelapse survival rate of patients with multiple myeloma （MM）. Methods Databases including PubMed, EMbase, The Cochrane Library （Issue 1, 2007） and Web of Science were searched to collect randomized controlled trials （RCTs） about thalidomide as first-line therapy for MM from 2006 to 2011. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed by using RevMan 5.1 software. Results A total of 16 RCTs involving 6 097 patients were included. The results of meta-analysis showed that, compared with the chemotherapy alone group, early application of thalidomide could significantly decrease the postrelapse survival rate （HR=1.23, 95%CI 1.05 to 1.45, P=0.002）. Subgroup analysis showed that, compared with the chemotherapy alone group, thalidomide maintenance therapy after autologous stem cell transplantation （ASCT） couldn＇t decrease the postrelapse survival rate （HR=0.90, 95%CI 0.57 to 1.41, P=0.64）, but thalidomide induction therapy before ASCT （HR=1.21, 95%CI 1.01 to 1.45, P=0.04） and thalidomide induction therapy before ASCT combined maintenance therapy after ASCT （HR=1.41, 95%CI 1.13 tol.76, P=0.002） could significantly decrease the postrelapse survival rate. Conclusion Current evidence shows that, thalidomide maintenance therapy after ASCT for MM is a better therapy regimen. It couldn＇t decrease the survival rate after recurrence, but could increase the disease-free survival （DFS） and overall survival （OS） of patients with MM. Due to the limited quality of included studies, the above conclusion still needs to be verified by more high quality studies.