沙利度胺在多发性骨髓瘤维持治疗中的Meta分析

Maintenance therapy with thalidomide in multiple myeloma:a Meta-analysis

目的：综合评价沙利度胺（Thal）对多发性骨髓瘤（MM）患者维持治疗的预后和安全性影响。方法系统检索 Pubmed、EMbase、Cochrane Library、中国生物医学文献数据库（CBM）、CNKI、维普和万方数据库截至2016年6月发表的关于 Thal 在 MM 维持治疗的随机对照研究（RCT），采用 RevMan 5.2软件行 Meta 分析。结果最终纳入11个 RCT，共4694例患者。Meta 分析结果显示，在 MM 患者维持治疗中，含 Thal 与不含 Thal 组无进展生存期（PFS）差异有统计学意义（HR=0.66，95% CI：0.61～0.72，P＜0.00001），但在总生存期（OS）方面无统计学差异（HR=0.95，95% CI：0.86～1.05，P=0.33）。亚组分析显示无论是否进行自体造血干细胞移植（ASCT），含 Thal组均可延长 PFS 而不能使 MM 患者在 OS 方面获益。在安全性方面，含 Thal 组的血栓栓塞、乏力、神经病变、水肿、便秘的发生率显著增加（P 均＜0.05）。而高血糖、疼痛、肺炎、失眠、感染的发生率相当，差异无统计学意义（P 均＞0.05）。结论在 MM 维持治疗中，无论是否行 ASCT，Thal能明显延长患者 PFS，但增加了血栓栓塞、乏力、神经病变、水肿、便秘不良反应的发生率。

Objective To evaluate the prognosis and safety of the maintenance therapy in multiple myeloma (MM) patients with thalidomide (Thal). Methods We systematically searched Pubmed, EMbase, Cochrane Library, CBM, CNKI, VIP and Wanfang database for the literature relating RCT on the maintenance therapy of MM with Thal up to June 2016, followed by a Meta-analysis with the software RevMan 5.2. Results 11 RCTs were included in the analysis involving 4 694 patients. The results of Meta-analysis showed that, compared with non-Thal group, Thal group could significantly increase progression-free survival (PFS; HR=0.66, 95% CI: 0.61-0.72, P<0.000 01), but failed to prolong overall survival (OS; HR=0.95, 95% CI: 0.86-1.05, P=0.33). Subgroup analyses showed that Thal group had longer PFS but not OS, no matter whether had autologous hematopoietic stem cell transplantation (ASCT) or not. About adverse events, Thal treatment significantly increased the incidence of thrombosis, fatigue, neuropathy, edema, constipation (P<0.05). However there was no difference of the incidence of the high blood sugar, pain, pneumonia, insomnia, infection in two group (P>0.05). Conclusion Thal maintenance therapy improves PFS but not OS in MM patients, and increases risks of adverse events, including thrombosis, fatigue, neuropathy, edema, constipation.