Department of Hematology and Rheumatology, The First Affiliated Hospital of Fujian Medical University, Chating, Fuzhou, 350005, China.
Ann Hematol. 2013 Jul;92(7):935-43. doi: 10.1007/s00277-013-1711-7. Epub 2013 Mar 2.
Multiple myeloma (MM) is an incurable disease with a poor survival, which has not been affected even by high-dose chemotherapy. This systematic review was performed to assess the efficacy and safety of the novel agent bortezomib for patients with previously untreated MM. We systematically searched biomedical literature databases and identified randomized controlled trials (RCTs) comparing bortezomib with placebo, no bortezomib, or other active agents for patients with previously untreated MM. Overall survival (OS), reported as hazard ratio (HR) with 95% confidence interval (CI), was the primary outcome measure. The secondary outcomes included time to progression (TTP), progression-free survival (PFS), and response rates. Five RCTs involving 2,728 patients were included. Three trials compared bortezomib with no bortezomib, and two compared bortezomib with other active agents (vincristine ± adriamycin-based chemotherapy). All included RCTs had methodological shortcomings, including no or unclear allocation concealment and blinding. Compared with no bortezomib or vincristine-based chemotherapy, the bortezomib-based regimen significantly improved the OS of patients with previously untreated MM. HR was 0.71 (95% CI 0.55-0.93) and 0.77 (95% CI 0.60-0.99), respectively. However, when compared with the vincristine + adriamycin-based regimen, the OS was similar (HR = 0.87, 95% CI 0.57-1.33). TTP, PFS, and response rates were also improved in patients receiving bortezomib-based regimen. However, the risk of peripheral neuropathy was found to be significantly higher. In summary, bortezomib appears to improve survival and response rates of patients with previously untreated MM in spite of higher risk of peripheral neuropathy.
多发性骨髓瘤（MM）是一种无法治愈的疾病，患者生存状况较差，即使接受大剂量化疗也无济于事。本系统评价旨在评估新型药物硼替佐米治疗未经治疗的多发性骨髓瘤患者的疗效和安全性。我们系统地检索了生物医学文献数据库，并确定了比较硼替佐米与安慰剂、无硼替佐米或其他活性药物治疗未经治疗的多发性骨髓瘤患者的随机对照试验（RCT）。总生存期（OS），以风险比（HR）和 95%置信区间（CI）表示，是主要的观察终点。次要终点包括无进展生存期（TTP）、无进展生存期（PFS）和反应率。共纳入 5 项涉及 2728 名患者的 RCT。3 项试验比较了硼替佐米与无硼替佐米，2 项试验比较了硼替佐米与其他活性药物（长春新碱+阿霉素化疗）。所有纳入的 RCT 都存在方法学上的缺陷，包括无或不明确的分配隐藏和盲法。与无硼替佐米或长春新碱+阿霉素化疗相比，硼替佐米方案显著改善了未经治疗的多发性骨髓瘤患者的 OS。HR 分别为 0.71（95%CI 0.55-0.93）和 0.77（95%CI 0.60-0.99）。然而，与长春新碱+阿霉素化疗方案相比，OS 相似（HR=0.87，95%CI 0.57-1.33）。TTP、PFS 和反应率在接受硼替佐米方案治疗的患者中也得到了改善。然而，外周神经病变的风险显著增加。总之，尽管存在外周神经病变风险较高的情况，但硼替佐米似乎可以提高未经治疗的多发性骨髓瘤患者的生存率和反应率。
