Hospital Universitario 12 de Octubre, Madrid, Spain;
Sequenta, Inc., San Francisco, CA;
Blood. 2014 May 15;123(20):3073-9. doi: 10.1182/blood-2014-01-550020. Epub 2014 Mar 19.
We assessed the prognostic value of minimal residual disease (MRD) detection in multiple myeloma (MM) patients using a sequencing-based platform in bone marrow samples from 133 MM patients in at least very good partial response (VGPR) after front-line therapy. Deep sequencing was carried out in patients in whom a high-frequency myeloma clone was identified and MRD was assessed using the IGH-VDJH, IGH-DJH, and IGK assays. The results were contrasted with those of multiparametric flow cytometry (MFC) and allele-specific oligonucleotide polymerase chain reaction (ASO-PCR). The applicability of deep sequencing was 91%. Concordance between sequencing and MFC and ASO-PCR was 83% and 85%, respectively. Patients who were MRD(-) by sequencing had a significantly longer time to tumor progression (TTP) (median 80 vs 31 months; P < .0001) and overall survival (median not reached vs 81 months; P = .02), compared with patients who were MRD(+). When stratifying patients by different levels of MRD, the respective TTP medians were: MRD ≥10(-3) 27 months, MRD 10(-3) to 10(-5) 48 months, and MRD <10(-5) 80 months (P = .003 to .0001). Ninety-two percent of VGPR patients were MRD(+). In complete response patients, the TTP remained significantly longer for MRD(-) compared with MRD(+) patients (131 vs 35 months; P = .0009).
我们评估了 133 例至少达到非常好的部分缓解（VGPR）的一线治疗后多发性骨髓瘤（MM）患者的骨髓样本中基于测序的平台检测微小残留病（MRD）的预后价值。对识别出高频骨髓瘤克隆的患者进行深度测序，并使用IGH-VDJH、IGH-DJH 和 IGK 检测评估 MRD。结果与多参数流式细胞术（MFC）和等位基因特异性寡核苷酸聚合酶链反应（ASO-PCR）进行对比。深度测序的适用性为 91%。测序与 MFC 和 ASO-PCR 的一致性分别为 83%和 85%。通过测序检测为 MRD(-)的患者肿瘤进展时间（TTP）（中位数 80 对 31 个月；P<.0001）和总生存期（中位数未达到对 81 个月；P=.02）明显更长，与 MRD(+)的患者相比。当按不同水平的 MRD 对患者进行分层时，相应的 TTP 中位数分别为：MRD≥10(-3)为 27 个月，MRD 为 10(-3)至 10(-5)为 48 个月，MRD<10(-5)为 80 个月（P=.003 至<.0001）。92%的 VGPR 患者为 MRD(+)。在完全缓解患者中，MRD(-)的 TTP 仍明显长于 MRD(+)患者（131 对 35 个月；P=.0009）。
