Circulating tumor cells predict myeloma outcomes in patients treated with daratumumab, bortezomib, lenalidomide, and dexamethasone.

In this study, we analyzed CTC in the phase 3 PERSEUS/EMN017 trial. TE-NDMM patients were randomized (1:1) to D-VRd with daratumumab/lenalidomide maintenance (D-VRd group) or bortezomib/lenalidomide/dexamethasone (VRd) with lenalidomide maintenance (VRd group), both with transplant.

在这项研究中，我们分析了第三阶段PERSEUS/EMN017试验中的CTC。可移植的NDMM患者被随机（1:1）分配到D-VRd组（达雷妥尤单抗/雷那度胺维持治疗）或VRd组（硼替佐米/雷那度胺/地塞米松，随后雷那度胺维持治疗），两组均接受移植。

A subset of 451 of 709 patients from PERSEUS (D-VRd, 231/355; VRd, 220/354) had screening blood samples collected for CTC analysis by flow cytometry.

PERSEUS研究中，709名患者中有451名（D-VRd组，231/355；VRd组，220/354）收集了用于流式细胞术检测循环肿瘤细胞（CTC）的筛查血样。

CTC were detected in 370 patients (82%; median limit of detection, 0.0004%).

在370名患者中检测到CTC（82%；检测下限中位数为0.0004%）。

CTC were prognostic of progression-free survival(PFS), independent of other factors, as a continuous (hazard ratio[HR], 1.36 [95% confidence interval(CI), 1.15-1.60]; P< .001) and categorical variable (≥0.175% CTC-high, optimal threshold).

CTC是无进展生存期（PFS）的预后因素，独立于其他因素，无论是作为连续变量（风险比[HR]，1.36 [95%置信区间（CI），1.15-1.60]；P< .001）还是分类变量（≥0.175% CTC-高，最佳阈值）。

D-VRd improved PFS vs VRd in CTC-low patients (4-year rates: 88% vs 74%; HR, 0.42 [95% CI, 0.25-0.70]; P = .0013).

在CTC低患者中，D-VRd改善了PFS，与VRd相比（4年率：88%对74%；HR，0.42 [95%置信区间（CI），0.25-0.70]；P = .0013）。

Regardless of study treatment, minimal residual disease (MRD)-negativity rates were lower in CTC-high vs CTC-low patients (10-5: 52.2% vs 66.2%; 10-6: 34.8% vs 52.4%).

无论研究治疗如何，CTC高患者与CTC低患者相比，最小残留病灶（MRD）阴性率较低（10^-5：52.2%对66.2%；10^-6：34.8%对52.4%）。

D-VRd significantly increased MRD-negativity rates vs VRd among CTC-high (10-5: 69.4% vs 33.3%; 10-6: 47.2% vs 21.2%; both P< .05) and CTC-low patients (10-5: 74.4% vs 57.8%; 10-6: 65.6% vs 38.5%; both P< .001), with similar observations for sustained MRD-negativity.

D-VRd显著提高了CTC高（10^-5：69.4%对33.3%；10^-6：47.2%对21.2%；两者P< .05）和CTC低患者（10^-5：74.4%对57.8%；10^-6：65.6%对38.5%；两者P< .001）的MRD阴性率，与VRd相比，持续MRD阴性的情况也有类似的观察结果。

CTC levels are an independent prognostic factor in TE-NDMM treated with standard-of-care frontline quadruplet.

CTC水平是接受标准一线四联疗法治疗的TE-NDMM患者的独立预后因素。

D-VRd improved and sustained MRD-negativity rates in CTC-high and CTC-low, and improved PFS for CTC-low with a positive trend in CTC-high patients.

D-VRd改善并维持了CTC高和CTC低患者的MRD阴性率，并提高了CTC低患者的无进展生存期，CTC高患者也显示出积极的趋势。

This trial was registered at www.clinicaltrials.gov as #NCT03710603.

该试验已在www.clinicaltrials.gov上注册，注册号为#NCT03710603。