Bortezomib Induction and Maintenance Treatment in Patients With Newly Diagnosed Multiple Myeloma: Results of the Randomized Phase III HOVON-65/GMMG-HD4 Trial
Bortezomib Induction and Maintenance Treatment in Patients With Newly Diagnosed Multiple Myeloma: Results of the Randomized Phase III HOVON-65/GMMG-HD4 Trial
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DOI：
10.1200/jco.2011.39.6820
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发表时间：
2012-08-20
影响因子：
45.3
通讯作者：
Goldschmidt, Hartmut M.
中科院分区：
文献类型：
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作者：
Sonneveld, Pieter;Schmidt-Wolf, Ingo G. H.;Goldschmidt, Hartmut M.
PurposeWe调查硼替佐米在诱导和维持治疗期间是否能提高新诊断多发性骨髓瘤（MM）的生存率。患者和方法共有827例符合条件的新诊断症状性MM患者被随机分配接受长春新碱、多柔比星和地塞米松（VAD）或硼替佐米、多柔比星和地塞米松（PAD）诱导治疗，随后接受大剂量美法仑和自体干细胞移植。维持治疗包括沙利度胺50 mg（VAD）每天一次或硼替佐米1.3 mg/m（2）（PAD）每2周一次，持续2年。主要分析是无进展生存期（PFS）调整国际分期系统（ISS）stage.ResultsComplete反应（CR），包括近CR，是优于PAD诱导后（15%v31%; P <0.001）和硼替佐米维护（34%v49%; P <0.001）。中位随访41个月后，PAD组的PFS上级（中位28个月vs 35个月;风险比[ HR]，0.75; 95% CI，0.62 - 0.90; P = 0.002）。在多变量分析中，PAD组的总生存期（OS）更好（HR，0.77; 95% CI，0.60 - 1.00; P = 0.049）。在肌酐升高超过2 mg/dL的高危患者中，硼替佐米显著改善了PFS，中位PFS从13个月延长至30个月（HR，0.45; 95% CI，0.26 - 0.78; P = 0.004），OS中位数为21个月至54个月（HR，0.33; 95% CI，0.16 - 0.65; P <0.001）。在17 p13缺失的患者中也观察到了益处（中位PFS，12 vs 22个月; HR，0.47; 95% CI，0.26至0.86; P = 0.01;中位OS，24个月vs 54个月时未达到; HR，0.36; 95% CI，0.18至0.74;结论硼替佐米在诱导期和维持期可改善CR，并获得较好的上级PFS和OS。
PurposeWe investigated whether bortezomib during induction and maintenance improves survival in newly diagnosed multiple myeloma (MM).Patients and MethodsIn all, 827 eligible patients with newly diagnosed symptomatic MM were randomly assigned to receive induction therapy with vincristine, doxorubicin, and dexamethasone (VAD) or bortezomib, doxorubicin, and dexamethasone (PAD) followed by high-dose melphalan and autologous stem-cell transplantation. Maintenance consisted of thalidomide 50 mg (VAD) once per day or bortezomib 1.3 mg/m(2) (PAD) once every 2 weeks for 2 years. The primary analysis was progression-free survival (PFS) adjusted for International Staging System (ISS) stage.ResultsComplete response (CR), including near CR, was superior after PAD induction (15% v 31%; P < .001) and bortezomib maintenance (34% v 49%; P < .001). After a median follow-up of 41 months, PFS was superior in the PAD arm (median of 28 months v 35 months; hazard ratio [ HR], 0.75; 95% CI, 0.62 to 0.90; P = .002). In multivariate analysis, overall survival (OS) was better in the PAD arm (HR, 0.77; 95% CI, 0.60 to 1.00; P = .049). In high-risk patients presenting with increased creatinine more than 2 mg/dL, bortezomib significantly improved PFS from a median of 13 months to 30 months (HR, 0.45; 95% CI, 0.26 to 0.78; P = .004) and OS from a median of 21 months to 54 months (HR, 0.33; 95% CI, 0.16 to 0.65; P < .001). A benefit was also observed in patients with deletion 17p13 (median PFS, 12 v 22 months; HR, 0.47; 95% CI, 0.26 to 0.86; P = .01; median OS, 24 months v not reached at 54 months; HR, 0.36; 95% CI, 0.18 to 0.74; P = .003).ConclusionBortezomib during induction and maintenance improves CR and achieves superior PFS and OS.