High-dose busulfan-melphalan vs melphalan and reinforced VRD for newly diagnosed multiple myeloma: a phase 3 GEM trial.

We compared long-term outcomes of BUMEL vs MEL200 in the context of intensified bortezomib, lenalidomide, and dexamethasone (VRD) induction and consolidation therapies.

我们比较了在强化的硼替佐米、雷那度胺和地塞米松（VRD）诱导和巩固治疗背景下，BUMEL与MEL200的长期疗效。

GEM12 was a phase 3 trial for patients with newly diagnosed multiple myeloma (NDMM) eligible for ASCT including 6 reinforced VRD cycles followed by ASCT conditioned with BUMEL or MEL200 and 2 VRD consolidation cycles.

GEM12是一项针对新诊断的多发性骨髓瘤（NDMM）患者的III期临床试验，这些患者有资格接受自体干细胞移植（ASCT）。试验包括6个强化的VRD（硼替佐米、来那度胺、地塞米松）周期，随后是使用BUMEL或MEL200条件下的ASCT，以及2个VRD巩固周期。

The primary end point was PFS.

主要终点是无进展生存期（PFS）。

Subgroup analyses were based on International Staging System (ISS) stages and high-risk genetic abnormalities.

亚组分析基于国际分期系统（ISS）阶段和高风险遗传异常。

Patients were randomized with an open-label 2 × 2 factorial design and 1:1:1:1 allocation ratio to ensure the balance between the GEM12 and the subsequent phase 3 GEM14 trial. Between 2013 and 2015, 458 patients were randomized (BUMEL, n = 230; MEL200, n = 228).

患者采用开放标签的2×2因素设计和1:1:1:1的分配比例进行随机分组，以确保GEM12试验和随后的GEM14第三阶段试验之间的平衡。在2013年至2015年间，共有458名患者被随机分配（BUMEL，n=230；MEL200，n=228）。

The 10⁻⁶ MRD-negative rate was 63%, 68% for BUMEL vs 58% for MEL200 (odds ratio, 1.51; P = .035).

10⁻⁶ MRD阴性率在BUMEL组为68%，而在MEL200组为58%（比值比，1.51；P = .035）。

The median PFS was 89 months for BUMEL and 73.1 for MEL200 (hazard ratio, 0.89 [95% confidence interval, 0.70-1.14]; P = .3).

BUMEL组的中位无进展生存期为89个月，而MEL200组为73.1个月（风险比，0.89 [95% 置信区间，0.70-1.14]；P = .3）。

BUMEL showed benefit for patients with ISS stages II or III, t(14;16), and del(1p).

BUMEL对ISS II期或III期、t(14;16)和del(1p)的患者显示出益处。

For subcohorts ISS stages II or III treated with BUMEL and ISS I treated with MEL200 the median PFS was 96.5 months (95% confidence interval, 76 to not estimable).

对于接受BUMEL治疗的ISS II期或III期亚组和接受MEL200治疗的ISS I期亚组，中位无进展生存期为96.5个月（95%置信区间，76至不可估计）。

No safety concerns were observed.

未观察到任何安全问题。

After a median follow-up of 8.4 years, GEM2012 demonstrated one of the longest PFS values reported in patients with NDMM, with significant differences favoring BUMEL in advanced ISS stages.

中位随访8.4年后，GEM2012在新诊断多发性骨髓瘤（NDMM）患者中显示出报告中较长的无进展生存（PFS）值之一，特别是在高级ISS分期中，BUMEL显示出显著的生存优势。

The trial was registered at www.ClinicalTrials.gov as #NCT01916252 and at European Union Drug Regulating Authorities Clinical Trials as EudraCT 2012-005683-10.

该试验已在www.ClinicalTrials.gov上注册，注册号为#NCT01916252，并在欧洲联盟药品监管机构临床试验中注册，注册号为EudraCT 2012-005683-10。