Monitoring multiple myeloma in the peripheral blood based on cell-free DNA and circulating plasma cells.
Monitoring multiple myeloma in the peripheral blood based on cell-free DNA and circulating plasma cells.
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DOI：
10.1007/s00277-022-04771-5
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发表时间：
2022-04
影响因子：
3.5
通讯作者：
Hoffmann J
中科院分区：
文献类型：
--
作者：
Mack EKM;Hartmann S;Ross P;Wollmer E;Mann C;Neubauer A;Brendel C;Hoffmann J
随着新型高效的多发性骨髓瘤（MM）治疗方法的出现，传统的血清学监测似乎不足以评估疗效和预测复发。此外，治疗性抗体的干扰阻碍了MM的血清学研究。通过下一代测序（NGS）或多参数流式细胞术（MFC）检测恶性浆细胞克隆克服了这些困难，并且可以通过靶向循环无细胞DNA （cfDNA）或循环浆细胞（cpc）在外周血（pB）中进行，从而也避免了侵入性取样过程。在这里，我们应用了cfDNA中VJ轻链（LC）重排的NGS和磁性富集cd138阳性cpc （me-MFC）的MFC来研究未选择的MM患者的疾病负担。114/130（87.7%）份cfDNA样本测序成功，196/205（95.6%）份cfDNA样本me-MFC结果可分析。在初次诊断或复发（ID/RD）时采集的样本中，38.9%可检测到MM克隆，但在完全缓解（CR）期间采集的样本中，仅11.8%可检测到MM克隆。83.3%的ID/RD样本和9.9%的CR样本中存在循环MM浆细胞。在非常好的部分缓解或CR期间采集的样本中，NGS或me-MFC残留疾病评估的一致性为80%。值得注意的是，4/4 （NGS）和5/8 （me-MFC）阳性CR样本来自寡分泌或非分泌性骨髓瘤患者。如果脑脊液中有残留骨髓瘤的证据，则进展时间较短。总之，我们的研究结果表明，我们的两种新的分析方法可以准确地指示MM的病程，对于监测血清学上无法追踪的疾病患者可能特别有价值。在线版本包含补充材料，可在10.1007/s00277-022-04771-5获得。
With the advent of novel, highly effective therapies for multiple myeloma (MM), classical serologic monitoring appears insufficient for response assessment and prediction of relapse. Moreover, serologic studies in MM are hampered by interference of therapeutic antibodies. The detection of malignant plasma cell clones by next generation sequencing (NGS) or multiparameter flow cytometry (MFC) circumvents these difficulties and can be performed in the peripheral blood (pB) by targeting circulating cell-free DNA (cfDNA) or circulating plasma cells (CPCs), thus also avoiding an invasive sampling procedure. Here, we applied NGS of VJ light chain (LC) rearrangements in cfDNA and MFC of magnetically-enriched CD138-positive CPCs (me-MFC) to investigate disease burden in unselected MM patients. Sequencing was successful for 114/130 (87.7%) cfDNA samples and me-MFC results were analyzable for 196/205 (95.6%) samples. MM clones were detectable in 38.9% of samples taken at initial diagnosis or relapse (ID/RD), but only in 11.8% of samples taken during complete remission (CR). Circulating MM plasma cells were present in 83.3% of ID/RD samples and 9.9% of CR samples. Residual disease assessment by NGS or me-MFC in samples taken during very good partial remission or CR was 80% concordant. Notably, 4/4 (NGS) and 5/8 (me-MFC) positive CR samples were from patients with oligo- or non-secretory myeloma. The time to progression was shorter if there was evidence of residual myeloma in the pB. Together, our findings indicate that our two novel analytical approaches accurately indicate the course of MM and may be particularly valuable for monitoring patients with serologically non-trackable disease. The online version contains supplementary material available at 10.1007/s00277-022-04771-5.
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影响因子：
16.6
作者：
Kis O;Kaedbey R;Chow S;Danesh A;Dowar M;Li T;Li Z;Liu J;Mansour M;Masih-Khan E;Zhang T;Bratman SV;Oza AM;Kamel-Reid S;Trudel S;Pugh TJ
通讯作者：
Pugh TJ
VS38C和CD38-MultiePitope抗体可为多发性骨髓瘤患者提供高度可比的最小残留疾病数据。
影响因子：
3.5
作者：
Broijl A;de Jong ACM;van Duin M;Sonneveld P;Kühnau J;van der Velden VHJ
通讯作者：
van der Velden VHJ
影响因子：
7.5
作者：
Mazzotti, Celine;Buisson, Laure;Corre, Jill
通讯作者：
Corre, Jill
影响因子：
12.8
作者：
Medina A;Puig N;Flores-Montero J;Jimenez C;Sarasquete ME;Garcia-Alvarez M;Prieto-Conde I;Chillon C;Alcoceba M;Gutierrez NC;Oriol A;Rosinol L;Bladè J;Gironella M;Hernandez MT;Gonzalez-Calle V;Cedena MT;Paiva B;San-Miguel JF;Lahuerta JJ;Mateos MV;Martinez-Lopez J;Orfao A;Gonzalez M;Garcia-Sanz R
通讯作者：
Garcia-Sanz R
影响因子：
4.1
作者：
Biancon, Giulia;Gimondi, Silvia;Corradini, Paolo
通讯作者：
Corradini, Paolo