PDF(Pubmed)
Abstract：
UNASSIGNED: Limited data are available on the concordance between multiparameter flow cytometry (MFC) and next-generation sequencing (NGS) for minimal residual disease (MRD) detection in a large trial for multiple myeloma (MM) patients.
UNASSIGNED: MRD was explored in the FORTE trial for transplant-eligible MM patients randomised to three carfilzomib-based induction-intensification-consolidation treatments and carfilzomib-lenalidomide (KR) vs R maintenance. MRD was assessed by 8-colour 2nd-generation flow cytometry in patients with ≥very good partial response before maintenance. NGS was performed in case of suspected complete response (CR) in a correlative subanalysis. Biological/prognostic concordance between MFC and NGS, conversion to MRD negativity during maintenance, and 1-year/2-year sustained MRD negativity were explored.
UNASSIGNED: Between September 28, 2015 and December 22, 2021, 2020 samples were available for MFC and 728 for the simultaneous MFC/NGS correlation in the \"suspected CR population\". Median follow-up was 62 months. Biological agreement was 87% at the 10-5 and 83% at the 10-6 cut-offs. A remarkable prognostic concordance was observed: hazard ratios in MFC-MRD and NGS-MRD-negative vs -positive patients were 0.29 and 0.27 for progression-free survival (PFS) and 0.35 and 0.31 for overall survival, respectively (p < 0.05). During maintenance, 4-year PFS was 91% and 97% in 1-year sustained MFC-MRD-negative and NGS-MRD-negative patients (10-5), respectively, and 99% and 97% in 2-year sustained MFC-MRD-negative and NGS-MRD-negative patients, regardless of treatment received. The conversion rate from pre-maintenance MRD positivity to negativity during maintenance was significantly higher with KR vs R both by MFC (46% vs 30%, p = 0.046) and NGS (56% vs 30%, p = 0.046).
UNASSIGNED: The significant biological/clinical concordance between MFC and NGS at the same sensitivity suggests their possible use in the evaluation of one of the currently strongest predictors of outcome.
UNASSIGNED: Amgen, Celgene/Bristol Myers Squibb, Multiple Myeloma Research Foundation.
UNASSIGNED: MRD was explored in the FORTE trial for transplant-eligible MM patients randomised to three carfilzomib-based induction-intensification-consolidation treatments and carfilzomib-lenalidomide (KR) vs R maintenance. MRD was assessed by 8-colour 2nd-generation flow cytometry in patients with ≥very good partial response before maintenance. NGS was performed in case of suspected complete response (CR) in a correlative subanalysis. Biological/prognostic concordance between MFC and NGS, conversion to MRD negativity during maintenance, and 1-year/2-year sustained MRD negativity were explored.
UNASSIGNED: Between September 28, 2015 and December 22, 2021, 2020 samples were available for MFC and 728 for the simultaneous MFC/NGS correlation in the \"suspected CR population\". Median follow-up was 62 months. Biological agreement was 87% at the 10-5 and 83% at the 10-6 cut-offs. A remarkable prognostic concordance was observed: hazard ratios in MFC-MRD and NGS-MRD-negative vs -positive patients were 0.29 and 0.27 for progression-free survival (PFS) and 0.35 and 0.31 for overall survival, respectively (p < 0.05). During maintenance, 4-year PFS was 91% and 97% in 1-year sustained MFC-MRD-negative and NGS-MRD-negative patients (10-5), respectively, and 99% and 97% in 2-year sustained MFC-MRD-negative and NGS-MRD-negative patients, regardless of treatment received. The conversion rate from pre-maintenance MRD positivity to negativity during maintenance was significantly higher with KR vs R both by MFC (46% vs 30%, p = 0.046) and NGS (56% vs 30%, p = 0.046).
UNASSIGNED: The significant biological/clinical concordance between MFC and NGS at the same sensitivity suggests their possible use in the evaluation of one of the currently strongest predictors of outcome.
UNASSIGNED: Amgen, Celgene/Bristol Myers Squibb, Multiple Myeloma Research Foundation.
摘要：
■在一项针对多发性骨髓瘤（MM）患者的大型试验中，用于微小残留病（MRD）检测的多参数流式细胞术（MFC）和下一代测序（NGS）之间的一致性数据有限。
■在FORTE试验中对符合移植资格的MM患者进行了探索，这些患者随机接受了三种基于卡非佐米的诱导-强化-巩固治疗以及卡非佐米-来那度胺（KR）与R维持治疗。在维持治疗前部分反应≥非常好的患者中，通过8色第二代流式细胞术评估MRD。在相关亚分析中，在怀疑完全缓解（CR）的情况下进行NGS。MFC和NGS之间的生物学/预后一致性，在维护期间转换为MRD负性，并探讨了1年/2年持续MRD阴性。
■在2015年9月28日至2021年12月22日之间，MFC和728个样本可用于“可疑CR人群”中的同时MFC/NGS相关性。中位随访时间为62个月。生物学一致性在10-5时为87％，在10-6截止时为83％。观察到显著的预后一致性：MFC-MRD和NGS-MRD阴性与阳性患者的无进展生存期（PFS）风险比分别为0.29和0.27，总生存期为0.35和0.31。分别为(p<0.05)。在维护期间,1年持续MFC-MRD阴性和NGS-MRD阴性患者的4年PFS分别为91％和97％（10-5），分别,99%和97%的2年持续MFC-MRD阴性和NGS-MRD阴性患者，无论接受何种治疗。通过MFC，KR与R两者从维护前MRD阳性到维护期间阴性的转化率均显着较高（46％vs30％，p=0.046)和NGS(56%vs30%，p=0.046)。
■MFC和NGS在相同敏感性下的显着生物学/临床一致性表明它们可能用于评估目前最强的结果预测因子之一。
■安进，Celgene/百时美施贵宝,多发性骨髓瘤研究基金会。
■在FORTE试验中对符合移植资格的MM患者进行了探索，这些患者随机接受了三种基于卡非佐米的诱导-强化-巩固治疗以及卡非佐米-来那度胺（KR）与R维持治疗。在维持治疗前部分反应≥非常好的患者中，通过8色第二代流式细胞术评估MRD。在相关亚分析中，在怀疑完全缓解（CR）的情况下进行NGS。MFC和NGS之间的生物学/预后一致性，在维护期间转换为MRD负性，并探讨了1年/2年持续MRD阴性。
■在2015年9月28日至2021年12月22日之间，MFC和728个样本可用于“可疑CR人群”中的同时MFC/NGS相关性。中位随访时间为62个月。生物学一致性在10-5时为87％，在10-6截止时为83％。观察到显著的预后一致性：MFC-MRD和NGS-MRD阴性与阳性患者的无进展生存期（PFS）风险比分别为0.29和0.27，总生存期为0.35和0.31。分别为(p<0.05)。在维护期间,1年持续MFC-MRD阴性和NGS-MRD阴性患者的4年PFS分别为91％和97％（10-5），分别,99%和97%的2年持续MFC-MRD阴性和NGS-MRD阴性患者，无论接受何种治疗。通过MFC，KR与R两者从维护前MRD阳性到维护期间阴性的转化率均显着较高（46％vs30％，p=0.046)和NGS(56%vs30%，p=0.046)。
■MFC和NGS在相同敏感性下的显着生物学/临床一致性表明它们可能用于评估目前最强的结果预测因子之一。
■安进，Celgene/百时美施贵宝,多发性骨髓瘤研究基金会。
