达雷妥尤单抗-硼替佐米-沙利度胺-地塞米松用于新诊断骨髓瘤：CASSIOPEIA微小残留病结果

Daratumumab-Bortezomib-Thalidomide-Dexamethasone for Newly Diagnosed Myeloma: CASSIOPEIA Minimal Residual Disease Results.

作者信息

Corre Jill, Vincent Laure, Moreau Philippe, Hebraud Benjamin, Hulin Cyrille, Béné Marie-Christine, Broijl Annemiek, Caillot Denis, Delforge Michel, Dejoie Thomas, Facon Thierry, Lambert Jerome, Leleu Xavier, Macro Margaret, Perrot Aurore, Zweegman Sonja, Filleron Thomas, Cabarrou Bastien, van de Donk Niels W C J, Mahéo Sabrina, Hua Winnie, Wang Jianping, Krevvata Maria, Vanquickelberghe Véronique, de Boer Carla, Tuozzo Alba, Borgsten Fredrik, Rowe Melissa, Carson Robin, Wuilleme Soraya, Sonneveld Pieter

机构信息

Unité de Genomique du Myélome, IUC- T Oncopole, TOULOUSE, United States.

CHU Montpellier, Montpellier, France.

出版信息

Blood. 2025 Mar 24. doi: 10.1182/blood.2024027620.

DOI:10.1182/blood.2024027620

PMID:40127397

Abstract

Previous results from CASSIOPEIA (NCT02541383) demonstrated superior progression-free survival (PFS) and minimal residual disease (MRD) negativity with the addition of daratumumab to bortezomib, thalidomide, and dexamethasone (VTd) induction/consolidation and with daratumumab maintenance versus observation in transplant-eligible newly diagnosed multiple myeloma (NDMM). Here, we present long-term MRD status and PFS outcomes after an 80.1-month median follow-up. Patients were randomly assigned (1:1) to daratumumab plus VTd (D-VTd) or VTd induction/consolidation; patients remaining on study were re-randomized to daratumumab maintenance or observation for £2 years. MRD status was assessed at pre-defined timepoints during each study phase. D-VTd improved overall MRD-negativity rates (10-5) post-induction (34.6% vs 23.1%; P<0.0001) and post-consolidation (63.7% vs 43.7%; P<0.0001) and provided PFS benefit, regardless of post-induction MRD status, versus VTd alone. Daratumumab maintenance improved overall MRD-negativity rates over observation, regardless of induction/consolidation treatment (D-VTd/daratumumab vs D-VTd/observation: 10-5, 77.3% vs 70.7% [P=0.0417]; 10-6, 60.7% vs 52.0% [P=0.0365]; VTd/daratumumab vs VTd/observation: 10-5, 70.9% vs 51.2% [P<0.0001]; 10-6, 48.4% vs 30.7% [P<0.0001]), and improved MRD-negativity rates, regardless of risk status, as defined by cytogenetic abnormalities or revised International Staging System score. Further, daratumumab maintenance provided PFS benefit versus observation, regardless of induction/consolidation treatment and post-consolidation MRD status. D-VTd followed by daratumumab maintenance consistently produced the highest landmark, accumulative, and sustained MRD-negativity rates (10-5 and 10-6), translating to superior long-term PFS outcomes. These results demonstrate that daratumumab-based induction/consolidation followed by daratumumab maintenance resulted in the deepest and most durable MRD negativity, leading to superior PFS outcomes.

摘要

CASSIOPEIA（NCT02541383）先前的研究结果表明，在适合移植的新诊断多发性骨髓瘤（NDMM）患者中，在硼替佐米、沙利度胺和地塞米松（VTd）诱导/巩固治疗中添加达雷妥尤单抗以及采用达雷妥尤单抗维持治疗，相较于观察等待，无进展生存期（PFS）更优，微小残留病（MRD）阴性率更高。在此，我们报告了中位随访80.1个月后的长期MRD状态和PFS结果。患者被随机分配（1:1）接受达雷妥尤单抗联合VTd（D-VTd）或VTd诱导/巩固治疗；继续参与研究的患者被再次随机分配接受达雷妥尤单抗维持治疗或观察等待2年。在每个研究阶段的预定义时间点评估MRD状态。D-VTd方案改善了诱导后（34.6%对23.1%；P<0.0001）和巩固后（63.7%对43.7%；P<0.0001）的总体MRD阴性率，并且无论诱导后MRD状态如何，与单独使用VTd相比，均能提供PFS获益。无论诱导/巩固治疗如何，达雷妥尤单抗维持治疗相较于观察等待均提高了总体MRD阴性率（D-VTd/达雷妥尤单抗对D-VTd/观察等待：10-5，77.3%对70.7%[P=0.0417]；10-6，60.7%对52.0%[P=0.0365]；VTd/达雷妥尤单抗对VTd/观察等待：10-5，70.9%对51.2%[P<0.0001]；10-6，48.4%对30.7%[P<0.0001]），并且无论根据细胞遗传学异常或修订的国际分期系统评分定义的风险状态如何，均提高了MRD阴性率。此外，无论诱导/巩固治疗和巩固后MRD状态如何，达雷妥尤单抗维持治疗相较于观察等待均能提供PFS获益。D-VTd方案序贯达雷妥尤单抗维持治疗始终产生最高的标志性、累积性和持续性MRD阴性率（10-5和10-6），转化为更优的长期PFS结果。这些结果表明，基于达雷妥尤单抗的诱导/巩固治疗序贯达雷妥尤单抗维持治疗可导致最深且最持久的MRD阴性，从而带来更优的PFS结果。