来那度胺治疗难治复发慢性淋巴细胞白血病疗效及不良反应的meta分析

Efficacy and adverse effect of lenalidomide in relapsed/refractory chronic lymphocytic leukemia patient: a meta-analysis

目的:评价来那度胺(L)±CD20单抗治疗难治复发慢性淋巴细胞白血病(CLL)的疗效和不良反应。方法:计算机检索Pub Med/Medline,Embase,中国期刊网数据库(CNKI)、万方数据库(VIP)、维普网,中国生物医学文献数据库(CBM),以及Clinical Trials.gov、美国食品药品监督管理局(FDA)和欧洲药品管理局(EMA)网站,对纳入的文献进行治疗评价并提取相关数据。采用R软件对提取数据进行meta分析,计算有效率、不良反应发生率、相对风险率(RRR)和95%置信区间(95%CI)。结果:共纳入17个队列研究进行后续分析。结果显示,来那度胺治疗的总有效率(完全缓解+部分缓解)为42.10%(95%CI:32.41%~52.43%,I2=79.1%),采用L+CD20单抗治疗方案的有效率为60.01%(95%CI:53.88%~65.86%),而采用L单药治疗方案的有效率为24.31%(95%CI:16.34%~34.67%)。3~4级中性粒细胞减少为来那度胺最常见的不良反应,发生率为61.98%(95%CI:54.01%~69.35%)。3~4级血小板减少和血红蛋白降低的发生率分别为21.33%(95%CI:14.15%~30.84%)和11.32%(95%CI:8.46%~14.98%)。3~4级感染事件的发生率为33.52%(95%CI:28.99%~38.38%)。其他报道较多的不良反应包括"燃瘤作用",静脉血栓和疲劳等。结论:在难治复发CLL的治疗中,对于欧美外无法获得新药国家的患者及对此类新药耐药的患者,含有来那度胺的方案也许是有效的治疗手段。

Objective： Efficacy and adverse effect of lenalidomide monotherapy or in combination with anti-CD20 monoclonal antibody （mAbs） in relapsed/refractory chronic lymphocytic leukemia was evaluated. Methods： We conducted a literature search using the PubMed/Medline and Embase database, as well as Chinese language databases, including the Chinese Biomedical Literature Database, and Wanfang. We also searched the Cochrane Library for any recent systematic review on the subject, the ClinicalTrials.gov database, the websites of European Medicines Agency （EMA） and US Food and Drug Administration （FDA）. R software and was used for all statistical analyses. Results： 17 cohort studies were included in the final analyses. Pooled estimates of cumulative prevalence of total ORR was 42.10% （95%CI：32.41%-52.43%）. The pooled ORR in regimen with lenalidomide plus anti-CD20 antibody and lenalidomide mono-therapy are 60.01% （95% CI ：53.86%-65.86%） and 24.31%（95% CI：16.34%-34.67%） respectively.Cumulative prevalence of neutropenia was 61.98%（95% CI, 54.01%-69.35%）. For thrombocytopenia and anemia, cumulative prevalence were 21.33%（95% CI：14.15%-30.84%）and 11.32%（95% CI：8.46%-14.98%） respectively. Moreover, cumulative prevalence of infection rate was33.52% （95% CI：28.99%-38.38%）. Other adverse effect included tumor flare, deep vein thrombosis and fatigue.Conclusion： Lenalidomide is a considerable regimen for relapsed/refractory CLL patient.