Background/Objectives: Minimal residual disease (MRD) persists in most multiple myeloma (MM) patients, causing relapse despite deep remissions. Repeatability of MRD detection in MM bone marrow (BM) samples is limited, underscoring the need for blood-based monitoring approaches that can allow more thorough disease surveillance.Methods: This study compares tumor detection rates in BM-derived DNA with different blood-derived DNA sources, using next-generation sequencing of the immunoglobulin locus (NGS-IG). CD138-targeted immunomagnetic enrichment of circulating tumor cells (CTCs) followed by vacuum evaporation to concentrate DNA was used to optimize the tumor detection rate.Results: Tumor DNA was detected in 76%, 88% and 100% of cell-free DNA, peripheral blood-derived mononuclear cells, DNA and enriched CTC-DNA samples of patients with active myeloma, respectively. These data indicate that enriched CTC samples were the most informative for evaluation of disease detection with NGS-IG in patients with active myeloma. MRD detection was performed in paired BM and enriched CTC-DNA samples from 37 patients in remission. MRD positivity was found in the BM of 24 patients, with half of them (12/24) also showing the presence of MRD when enriched CTC-DNA was used. Interestingly, time to progression (TTP) of enriched CTC MRD-negative/BM MRD-positive patients was comparable to that of double MRD-negative (BM and CTC) patients. Moreover, double positive patients showed a trend to earlier relapses.Conclusions: Our data suggest that NGS-IG analysis with enriched CTC-DNA may offer improved predictive abilities for relapse in multiple myeloma compared to the currently used BM-DNA-based tumor detection method.
背景/目的：微小残留病（MRD）在大多数多发性骨髓瘤（MM）患者中持续存在，导致即使达到深度缓解后仍会复发。MM骨髓（BM）样本中MRD检测的可重复性有限，这凸显了需要基于血液的监测方法以实现更全面的疾病监测。方法：本研究采用免疫球蛋白基因座的新一代测序（NGS-IG），比较了BM来源DNA与不同血液来源DNA的肿瘤检出率。通过CD138靶向免疫磁珠富集循环肿瘤细胞（CTCs），并采用真空蒸发浓缩DNA，以优化肿瘤检出率。结果：在活动性骨髓瘤患者中，游离DNA、外周血来源单核细胞DNA以及富集CTC-DNA样本中肿瘤DNA的检出率分别为76%、88%和100%。这些数据表明，富集CTC样本对于活动性骨髓瘤患者使用NGS-IG进行疾病检测评估最具信息价值。对37名缓解期患者的配对BM和富集CTC-DNA样本进行了MRD检测。24名患者的BM中检测到MRD阳性，其中一半（12/24）在使用富集CTC-DNA时也显示存在MRD。有趣的是，富集CTC MRD阴性/BM MRD阳性患者的疾病进展时间（TTP）与双MRD阴性（BM和CTC）患者相当。此外，双阳性患者显示出更早复发的趋势。结论：我们的数据表明，与目前使用的基于BM-DNA的肿瘤检测方法相比，采用富集CTC-DNA的NGS-IG分析可能为多发性骨髓瘤的复发提供更优的预测能力。
肿瘤(癌症)患者之家