Triplet Therapy, Transplantation, and Maintenance until Progression in Myeloma.
Triplet Therapy, Transplantation, and Maintenance until Progression in Myeloma.
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DOI：
10.1056/nejmoa2204925
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发表时间：
2022-07-14
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在新诊断的多发性骨髓瘤患者中，在三联疗法（来那度胺、硼替佐米和地塞米松[RVD]）基础上增加自体干细胞移植（ASCT），随后进行来那度胺维持治疗直至疾病进展的影响尚不清楚。在这项III期试验中，患有症状性骨髓瘤的成人（18至65岁）接受了一个周期的RVD治疗。我们将这些患者以1：1的比例随机分配，接受两个额外的RVD周期加干细胞动员，然后是五个额外的RVD周期（RVD单独组）或高剂量美法仑加ASCT，然后是两个额外的RVD周期（移植组）。两组均接受来那度胺治疗，直至出现疾病进展、不可接受的副作用或两者兼而有之。主要终点是无进展生存期。在中位随访76.0个月时，RVD单独组357例患者和移植组365例患者中，发生了328起疾病进展或死亡事件; RVD单独组的风险比移植组高53%（风险比，1.53; 95%置信区间[CI]，1.23 - 1.91; P<0.001）;中位无进展生存期分别为46.2个月和67.5个月。部分缓解或更好的患者比例在RVD组为95.0%，在移植组为97.5%（P = 0.55）;完全缓解或更好的患者比例分别为42.0%和46.8%（P = 0.99）。3级或以上的治疗相关不良事件发生率分别为78.2%和94.2%; 5年生存率分别为79.2%和80.7%（死亡风险比为1.10; 95%CI为0.73 - 1.65）。在多发性骨髓瘤成人患者中，RVD联合ASCT与RVD单药治疗相比，无进展生存期更长。未观察到总体生存获益。（由国家心肺血液研究所和其他机构资助; DETERMINATION ClinicalTrials.gov编号，NCT 01208662。
In patients with newly diagnosed multiple myeloma, the effect of adding autologous stem-cell transplantation (ASCT) to triplet therapy (lenalidomide, bortezomib, and dexamethasone [RVD]), followed by lenalidomide maintenance therapy until disease progression, is unknown. In this phase 3 trial, adults (18 to 65 years of age) with symptomatic myeloma received one cycle of RVD. We randomly assigned these patients, in a 1:1 ratio, to receive two additional RVD cycles plus stem-cell mobilization, followed by either five additional RVD cycles (the RVD-alone group) or high-dose melphalan plus ASCT followed by two additional RVD cycles (the transplantation group). Both groups received lenalidomide until disease progression, unacceptable side effects, or both. The primary end point was progression-free survival. Among 357 patients in the RVD-alone group and 365 in the transplantation group, at a median follow-up of 76.0 months, 328 events of disease progression or death occurred; the risk was 53% higher in the RVD-alone group than in the transplantation group (hazard ratio, 1.53; 95% confidence interval [CI], 1.23 to 1.91; P<0.001); median progression-free survival was 46.2 months and 67.5 months. The percentage of patients with a partial response or better was 95.0% in the RVD-alone group and 97.5% in the transplantation group (P = 0.55); 42.0% and 46.8%, respectively, had a complete response or better (P = 0.99). Treatment-related adverse events of grade 3 or higher occurred in 78.2% and 94.2%, respectively; 5-year survival was 79.2% and 80.7% (hazard ratio for death, 1.10; 95% CI, 0.73 to 1.65). Among adults with multiple myeloma, RVD plus ASCT was associated with longer progression-free survival than RVD alone. No overall survival benefit was observed. (Funded by the National Heart, Lung, and Blood Institute and others; DETERMINATION ClinicalTrials.gov number, NCT01208662.)