Abstract
The International Myeloma Working Group (IMWG) recently introduced the evaluation of minimal residual disease (MRD) within the multiple myeloma (MM) response criteria, and MRD negativity assessed inside and outside the bone marrow is currently considered the most powerful predictor of favorable long-term outcomes. However, MRD evaluation has thus far relied on flow-cytometry or molecular-based methods, despite the limitations associated with the patchy infiltration of bone marrow (BM) plasma cells and the presence of extra-medullary (EMD). On the contrary, imaging-based sensitive response assessment through the use of functional rather than morphological whole-body (WB) imaging techniques, such as positron emission tomography with computed tomography (PET/CT) and magnetic resonance imaging (MRI), likely is a promising strategy to overcome these limitations in evaluating response to therapy and in the assessment of the MRD status in MM patients. However, despite the significant advances in the development and availability of novel functional imaging techniques for MRD evaluation, a worldwide standardization of imaging criteria for acquisition, interpretation, and reporting is yet to be determined and will be object of future investigations.
Highlights
The International Myeloma Working Group (IMWG) recently introduced the evaluation of minimal residual disease (MRD) within the multiple myeloma (MM) response criteria, and MRD negativity assessed inside and outside the bone marrow is currently considered the most powerful predictor of favorable long-term outcomes
Besides the patchy infiltration of BMPCs and the presence of EMD, recent prospective studies monitoring patients with serial functional imaging and focal lesion (FL) biopsies have demonstrated that MM implies a great spatial heterogeneity which is proportional to the size of a focal lesions (FLs), and different disease clones with different genomic profiles may coexist in bone marrow (BM) and FLs [7,8]
Morphological whole-body (WB) imaging techniques should be replaced by functional evaluations, such as positron emission tomography with computed tomography (PET/CT) and magnetic resonance imaging (MRI), both providing a global representation of the tumor burden beyond osteolytic lesions and showing further prognostic markers such as EMD [10]
Summary
MRI examines the water and fat content within tissue and is the most sensitive tool to detect the infiltration of BM in MM, with no radiation exposure [32,33]. An MM typical MRI pattern is the following: hypo-intensity in T1-weighted, hyper-intensity in T2-weighted with fat suppression in opposed phase imaging, and increased contrast-enhancement in T1-weighted sequences. The minimal FOV in MM is the axial skeleton (spine and pelvis), but more and more space is nowadays given to the whole-body protocol (WB-MRI). This technique is based on T1, T1 non-fat-saturated, and STIR sequences, usually not requiring contrast infusion; the total scan time for a whole-body image is generally less than 20 min. Contrast agents are not always necessary, thanks to the high resolution of non-enhanced MRI for the BM, they are usually based on gadolinium, which is relatively inert, except in case of renal failure, where it can cause a nephrogenic systemic fibrosis. The process of acquisition, interpretation, and reporting of WB-MRI is very important, allowing the use of this technique to assess response to therapy; an attempt in this regard has very recently been proposed [35]
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