High Levels of Circulating Tumor Plasma Cells as a Key Hallmark of Aggressive Disease in Transplant-Eligible Patients With Newly Diagnosed Multiple Myeloma
High Levels of Circulating Tumor Plasma Cells as a Key Hallmark of Aggressive Disease in Transplant-Eligible Patients With Newly Diagnosed Multiple Myeloma
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DOI：
10.1200/jco.21.01393
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发表时间：
2022-09-20
影响因子：
45.3
通讯作者：
Gay, Francesca
中科院分区：
文献类型：
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作者：
Bertamini, Luca;Oliva, Stefania;Gay, Francesca
多发性骨髓瘤患者中高水平的循环肿瘤浆细胞（CTC-high）是侵袭性疾病的标志。我们的目的是确认预后的影响，并确定一个可能的临界值的CTC-高预测无进展生存期（PFS）和总生存期（OS），在伴随的风险特征和微小残留疾病（MRD）的情况下。在诊断时使用双管单平台流式细胞术（灵敏度4 x 10（-5））分析入组多中心随机FORTE临床试验（ClinicalTrials.gov标识符：NCT 02203643）的患者的CTC。采用第二代多参数流式细胞术（灵敏度10（-5））评估MRD。我们在一系列关于PFS结局的多变量（MV）考克斯比例风险回归分析中测试了不同的临界值，并选择了使Harrell's C统计量最大化的值。我们在MV分析中分析CTC对PFS和OS的影响，包括基线特征和MRD阴性。结果CTC分析在401例患者中进行，中位随访时间为50个月（四分位距，45-54个月）。CTC百分比与骨髓浆细胞百分比之间存在中度相关性（r = 0.38）。我们确定了0.07%的最佳CTC截止值（约5个细胞/μ L，C指数0.64）。在MV分析中，CTC高患者与CTC低患者相比，PFS（风险比，2.61; 95% CI，1.49至2.97，P <0.001; 4年PFS 38% v69%）和OS（风险比，2.61; 95% CI，1.49至4.56; P <0.001; 4年OS 68% v92%）显著更短。CTC水平，而不是骨髓浆细胞水平，影响结果。降低CTC高的负面影响的唯一因素是MRD阴性的实现（相互作用P = 0.039）。结论在多发性骨髓瘤中，CTC水平高于最佳截止值是一个易于评估的，强大的，独立的高危因素。MRD阴性的实现是调节其负面预后影响的最重要因素。(C)2022年美国临床肿瘤学会
PURPOSE High levels of circulating tumor plasma cells (CTC-high) in patients with multiple myeloma are a marker of aggressive disease. We aimed to confirm the prognostic impact and identify a possible cutoff value of CTC-high for the prediction of progression-free survival (PFS) and overall survival (OS), in the context of concomitant risk features and minimal residual disease (MRD) achievement.METHODS. CTC were analyzed at diagnosis with two-tube single-platform flow cytometry (sensitivity 4 x 10(-5)) in patients enrolled in the multicenter randomized FORTE clinical trial (ClinicalTrials.gov identifier: NCT02203643). MRD was assessed by second-generation multipara meter flow cytometry (sensitivity 10(-5)). We tested different cutoff values in series of multivariate (MV) Cox proportional hazards regression analyses on PFS outcome and selected the value that maximized the Harrell's C-statistic. We analyzed the impact of CTC on PFS and OS in a MV analysis including baseline features and MRD negativity.RESULTS CTC analysis was performed in 401 patients; the median follow-up was 50 months (interquartile range, 45-54 months). There was a modest correlation between the percentage of CTC and bone marrow plasma cells (r = 0.38). We identified an optimal CTC cutoff of 0.07% (approximately 5 cells/mu L, C-index 0.64). In MV analysis, CTC-high versus CTC-low patients had significantly shorter PFS (hazard ratio, 2.61; 95% CI, 1.49 to 2.97, P < .001; 4-year PFS 38% v69%) and OS (hazard ratio, 2.61; 95% CI, 1.49 to 4.56; P < .001; 4-year OS 68% v92%). The CTC levels, but not the bone marrow plasma cell levels, affected the outcome. The only factor that reduced the negative impact of CTC-high was the achievement of MRD negativity (interaction P = .039).CONCLUSION In multiple myeloma, increasing levels of CTC above an optimal cutoff represent an easy-to-assess, robust, and independent high-risk factor. The achievement of MRD negativity is the most important factor that modulates their negative prognostic impact. (C) 2022 by American Society of Clinical Oncology