Circulating tumor cells as a biomarker for response to therapy in multiple myeloma patients treated within the GMMG-MM5 trial.
Circulating tumor cells as a biomarker for response to therapy in multiple myeloma patients treated within the GMMG-MM5 trial.
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DOI：
10.1038/bmt.2017.91
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发表时间：
2017-08
影响因子：
4.8
通讯作者：
Goldschmidt H
中科院分区：
文献类型：
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作者：
Huhn S;Weinhold N;Nickel J;Pritsch M;Hielscher T;Hummel M;Bertsch U;Huegle-Doerr B;Vogel M;Angermund R;Hänel M;Salwender HJ;Weisel K;Dürig J;Görner M;Kirchner H;Peter N;Graeven U;Lordick F;Hoffmann M;Reimer P;Blau IW;Jauch A;Dembowsky K;Möhler T;Wuchter P;Goldschmidt H
在过去的15年中，由于新型药物的治疗，多发性骨髓瘤（MM）患者的结局得到了显著改善。1根据IMWG标准，高达75-90%的健康患者达到CR或非常好的部分缓解。2然而，大多数患者复发，表明存在微小残留病（MRD）。2事实上，用于检测MRD的高灵敏度方法，例如流式细胞术（MFC），等位基因特异性寡核苷酸PCR（ASO-PCR）和基于下一代测序（NGS）的测定，即使在达到临床CR的患者中也可以检测残留肿瘤细胞。3-5这些患者中存在MRD与PFS和总生存期较差相关。2-5最近，IMWG在MM缓解评估的新共识标准中承认了这些结果，该标准现在包括当患者达到CR时的MRD诊断和MRD阴性作为最深缓解。2沿着新的共识标准，IMWG指出，循环肿瘤细胞（CTC）应研究其作为反应和预后生物标志物的价值，因为CTC在诊断时已在大多数患者的PB中发现，并且其水平被确定为独立的预后因素。2在这项研究中，我们使用高灵敏度的ASO-PCR（Δ 10− 6）对接受新型药物和自体干细胞移植（ASCT）治疗的MM患者骨髓（BM）中的CTC和恶性浆细胞进行了纵向定量分析。我们的目的是检查CTC是否可以用作一种微创生物标志物，用于治疗MRD诊断以外的治疗反应，通常在患者达到CR时进行。样本采集自在德语骨髓瘤多中心组（GMMG，EudraCT编号2010-019173-16）6新诊断MM患者的开放标签、随机化、多中心III期临床试验MM 5中接受治疗的患者，以及在2014年春季之前达到CR或疑似CR的患者（表1; N= 41; 104 PB; 29 BM）。在诊断时和CR或疑似CR（CR N= 18/29）时采集BM样本，在诊断时和诱导治疗（IT：PAd或VCD）、ASCT和巩固治疗（Cons.）后采集PB样本。(CR N= 33/104;表1）。在HOVON-65/GMMG中接受治疗的11例患者的额外20份PB样本（诊断时和/或IT后，8对）-
During the last 15 years, the outcome of patients with multiple myeloma (MM) has improved significantly as a result of therapy with novel drugs. 1 Up to 75–90% of fit patients reach CR or very good partial response according to the IMWG criteria. 2 Nevertheless, most of the patients suffer from relapse, indicating the presence of minimal residual disease (MRD). 2 Indeed, highly sensitive methods for detection of MRD, such as multicolor flow cytometry (MFC), allele-specific oligonucleotide PCR (ASO-PCR) and next-generation sequencing (NGS)-based assays, enable detection of residual tumor cells even in patients achieving clinical CR. 3–5 Presence of MRD in these patients is associated with a worse PFS and overall survival. 2–5 Recently, the IMWG has acknowledged these results in the new consensus criteria for response assessment in MM, which now includes MRD diagnostics when patients have reached CR and MRD negativity as the deepest response. 2 Along with the new consensus criteria, the IMWG pointed out that circulating tumor cells (CTCs) should be investigated for their value as a biomarker for response and prognosis since CTCs have been found in the PB of most patients at the time of diagnosis, and their level was identified as an independent prognostic factor. 2 In this study, we performed a longitudinal quantitative analysis of CTCs and malignant plasma cells in the bone marrow (BM) in MM patients treated with novel agents and autologous stem cell transplantation (ASCT) using a highly sensitive ASO-PCR (⩽ 10− 6). We aimed to examine if CTCs could be used as a minimal invasive biomarker for response to therapy beyond MRD diagnostics that are usually performed when patients reach CR. Samples were collected from patients who were treated within the open-label, randomized, multicenter phase III clinical trial MM5 for newly diagnosed MM patients of the German-speaking Myeloma Multicenter Group (GMMG, EudraCT no. 2010-019173-16), 6 and who reached CR or suspected CR until spring 2014 (Table 1; N= 41; 104 PB; 29 BM). BM samples were collected at diagnosis and at the time of CR or suspected CR (CR N= 18/29), and PB samples were collected at diagnosis and after the induction therapy (IT: PAd or VCD), ASCT and consolidation therapy (Cons.)(CR N= 33/104; Table 1). Additional 20 PB samples (at diagnoses and/or after IT, eight pairs) of 11 patients treated within the HOVON-65/GMMG-
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DOI：
10.1038/nrclinonc.2014.239
发表时间：
2015-05
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
Mailankody S;Korde N;Lesokhin AM;Lendvai N;Hassoun H;Stetler-Stevenson M;Landgren O
通讯作者：
Landgren O
影响因子：
45.3
作者：
Sonneveld, Pieter;Schmidt-Wolf, Ingo G. H.;Goldschmidt, Hartmut M.
通讯作者：
Goldschmidt, Hartmut M.
影响因子：
45.3
作者：
Greipp, PR;San Miguel, J;Westin, J
通讯作者：
Westin, J
影响因子：
20.3
作者：
Neben, Kai;Lokhorst, Henk M.;Goldschmidt, Hartmut
通讯作者：
Goldschmidt, Hartmut
DOI：
10.3324/haematol.2009.016436
发表时间：
2010-07-01
期刊：
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
影响因子：
--
作者：
Neben, Kai;Jauch, Anna;Goldschmidt, Hartmut
通讯作者：
Goldschmidt, Hartmut