Functional Imaging for Therapeutic Assessment and Minimal Residual Disease Detection in Multiple Myeloma

Abstract

Serum markers and bone marrow examination are commonly used for monitoring therapy response in multiple myeloma (MM), but this fails to identify minimal residual disease (MRD), which frequently persists after therapy even in complete response patients, and extra-medullary disease escape. Positron emission tomography with computed tomography using 18F-deoxyglucose (FDG-PET/CT) is the reference imaging technique for therapeutic assessment and MRD detection in MM. To date, all large prospective cohort studies of transplant-eligible newly diagnosed MM patients have shown a strong and independent pejorative prognostic impact of not obtaining complete metabolic response by FDG-PET/CT after therapy, especially before maintenance. The FDG-PET/CT and MRD (evaluated by flow cytometry or next-generation sequencing at 10−5 and 10−6 levels, respectively) results are complementary for MRD detection outside and inside the bone marrow. For patients with at least a complete response, to reach double negativity (FDG-PET/CT and MRD) is a predictive surrogate for patient outcome. Homogenization of FDG-PET/CT interpretation after therapy, especially clarification of complete metabolic response definition, is currently underway. FDG-PET/CT does not allow MRD to be evaluated when it is negative at initial workup of symptomatic MM. New PET tracers such as CXCR4 ligands have shown high diagnostic value and could replace FDG in this setting. New sensitive functional magnetic resonance imaging (MRI) techniques such as diffusion-weighted MRI appear to be complementary to FDG-PET/CT for imaging MRD detection. The goal of this review is to examine the feasibility of functional imaging, especially FDG-PET/CT, for therapeutic assessment and MRD detection in MM.

Imaging of treatment response and minimal residual disease in multiple myeloma: state of the art WB-MRI and PET/CT

“…The same trial demonstrated the complementarity between imaging (both FDG-PET/CT and WB-MRI/DWI) and molecular techniques (flow cytometry) in defining the prognosis of patients [28]. Hence, for patients with CR, reaching double imaging and molecular MRD negativity is considered a predictive surrogate for patient outcome [127]. The prognostic value and therapeutic implications of positive imaging findings in patients with MRD bone marrow negativity deserve further evaluation.…”

Molecular Imaging in Multiple Myeloma—Novel PET Radiotracers Improve Patient Management and Guide Therapy

“…For instance, as recently demonstrated in a prospective setting, MRI and positron emission tomography/computed tomography with 2-deoxy-2-[ 18 F]fluoro-Dglucose (FDG PET/CT) were comparable for assessing bone lesions (6). Relative to PET, however, MRI identifies more diffuse bone lesions, whereas the tracer-based imaging technique is better suited to assess treatment response (6)(7)(8). Thus, as it can assess both bone marrow infiltration and extramedullary disease sites, the IMWG recommends FDG PET/CT, not only for suspected disease, but also in relapse or refractory scenarios (9).…”

Minimal Residual Disease in Multiple Myeloma: Something Old, Something New

“…However, in terms of response assessment, MRI has shown high-false positive rates, revealing FL that are not necessarily active. New functional MRI techniques have been developed in order to improve MRI results [124]. Diffusion-weighted magnetic resonance imaging (DW-MRI) examines the water movement at a cellular level within tissues.…”