Combination of flow cytometry and functional imaging for monitoring of residual disease in myeloma

Combination of flow cytometry and functional imaging for monitoring of residual disease in myeloma
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DOI:
10.1038/s41375-018-0329-0
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发表时间:
2019-07-01
期刊:
影响因子:
11.4
通讯作者:
Weinhold, N.
Weinhold, N.
中科院分区:
医学1区
文献类型:
--
作者:
Rasche, L.;Alapat, D.;Weinhold, N.

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髂骨是多发性骨髓瘤(MM)微小残留病(MRD)监测的取样部位。然而,疾病的分布往往是不同的,成像可以用来补充单一地点的MRD检测。我们调查了在一线或抢救治疗期间完全缓解(CR)的患者,在CR开始时进行了MRD流式细胞术和正电子发射断层扫描(PET)和弥散加权磁共振成像(DW-MRI)两种成像方式。残留灶性病变(FLS)在24%的一线患者中可检测到,与短期无进展生存(PFS)相关,DW-MRI在更多的患者中发现疾病。在一些患者中,FLS仅为PET阳性,表明这两种方法具有互补性。结合MRD和成像可以更好地预测结果,双阴性和双阳性特征分别定义了PFS良好和糟糕的组。在一线MRD阴性CR患者中,FLS是一种罕见的事件(12%)。相反,在抢救治疗期间获得MRD阴性CR的患者经常发生FLS(50%)。MRD阴性患者的多区域测序和成像显示空间分离的克隆持续存在。总之,我们认为DW-MRI是一种有前景的监测残留病变的工具,可以作为PET的补充,应该与MRD相结合。
The iliac crest is the sampling site for minimal residual disease (MRD) monitoring in multiple myeloma (MM). However, the disease distribution is often heterogeneous, and imaging can be used to complement MRD detection at a single site. We have investigated patients in complete remission (CR) during first-line or salvage therapy for whom MRD flow cytometry and the two imaging modalities positron emission tomography (PET) and diffusion-weighted magnetic resonance imaging (DW-MRI) were performed at the onset of CR. Residual focal lesions (FLs), detectable in 24% of first-line patients, were associated with short progression-free survival (PFS), with DW-MRI detecting disease in more patients. In some patients, FLs were only PET positive, indicating that the two approaches are complementary. Combining MRD and imaging improved prediction of outcome, with double-negative and double-positive features defining groups with excellent and dismal PFS, respectively. FLs were a rare event (12%) in first-line MRD-negative CR patients. In contrast, patients achieving an MRD-negative CR during salvage therapy frequently had FLs (50%). Multi-region sequencing and imaging in an MRD-negative patient showed persistence of spatially separated clones. In conclusion, we show that DW-MRI is a promising tool for monitoring residual disease that complements PET and should be combined with MRD.