Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
J Clin Oncol. 2021 Nov 10;39(32):3613-3622. doi: 10.1200/JCO.21.01045. Epub 2021 Sep 14.
To address the role of consolidation treatment for newly diagnosed, transplant eligible patients with multiple myeloma in a controlled clinical trial.
The EMN02/HOVON95 trial compared consolidation treatment with two cycles of bortezomib, lenalidomide, and dexamethasone (VRD) or no consolidation after induction and intensification therapy, followed by continuous lenalidomide maintenance. Primary study end point was progression-free survival (PFS).
Eight hundred seventy-eight eligible patients were randomly assigned to receive VRD consolidation (451 patients) or no consolidation (427 patients). At a median follow-up of 74.8 months, median PFS with adjustment for pretreatment was prolonged in patients randomly assigned to VRD consolidation (59.3 42.9 months, hazard ratio [HR] = 0.81; 95% CI, 0.68 to 0.96; = .016). The PFS benefit was observed across most predefined subgroups, including revised International Staging System (ISS) stage, cytogenetics, and prior treatment. Revised ISS3 stage (HR, 2.00; 95% CI, 1.41 to 2.86) and ampl1q (HR, 1.67; 95% CI, 1.37 to 2.04) were significant adverse prognostic factors. The median duration of maintenance was 33 months (interquartile range 13-86 months). Response ≥ complete response (CR) after consolidation versus no consolidation before start of maintenance was 34% versus 18%, respectively ( < .001). Response ≥ CR on protocol including maintenance was 59% with consolidation and 46% without ( < .001). Minimal residual disease analysis by flow cytometry in a subgroup of 226 patients with CR or stringent complete response or very good partial response before start of maintenance demonstrated a 74% minimal residual disease-negativity rate in VRD-treated patients. Toxicity from VRD was acceptable and manageable.
Consolidation treatment with VRD followed by lenalidomide maintenance improves PFS and depth of response in newly diagnosed patients with multiple myeloma as compared to maintenance alone.
在一项对照临床试验中探讨初诊、适合移植的多发性骨髓瘤患者巩固治疗的作用。
EMN02/HOVON95 试验比较了巩固治疗与两周期硼替佐米、来那度胺和地塞米松（VRD），或诱导和强化治疗后不进行巩固治疗，然后连续来那度胺维持治疗。主要研究终点是无进展生存期（PFS）。
878 例符合条件的患者被随机分配接受 VRD 巩固治疗（451 例）或不进行巩固治疗（427 例）。中位随访 74.8 个月，经预处理调整后，随机分配至 VRD 巩固治疗组的患者中位 PFS 延长（59.3 42.9 个月，风险比 [HR] = 0.81；95%CI，0.68 至 0.96； =.016）。该 PFS 获益见于大多数预先设定的亚组，包括修订后的国际分期系统（ISS）分期、细胞遗传学和既往治疗。修订后的 ISS3 期（HR，2.00；95%CI，1.41 至 2.86）和扩增 1q（HR，1.67；95%CI，1.37 至 2.04）是显著的不良预后因素。维持治疗的中位持续时间为 33 个月（四分位间距 13-86 个月）。巩固治疗后与不进行巩固治疗相比，在开始维持治疗前，缓解率≥完全缓解（CR）分别为 34%和 18%（ <.001）。巩固治疗后包括维持治疗的方案缓解率≥CR 为 59%，而不进行巩固治疗为 46%（ <.001）。在开始维持治疗前有 226 例 CR 或严格意义上的完全缓解或非常好的部分缓解的患者亚组中，采用流式细胞术进行微小残留病分析显示，VRD 治疗患者微小残留病阴性率为 74%。VRD 的毒性是可接受和可管理的。
与单纯维持治疗相比，初诊多发性骨髓瘤患者采用 VRD 巩固治疗加来那度胺维持治疗可改善 PFS 和缓解深度。
