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

AbstractBone imaging has been intimately associated with the diagnosis and staging of multiple myeloma (MM) for more than 5 decades, as the presence of bone lesions indicates advanced disease and dictates treatment initiation. The methods used have been evolving, and the historical radiographic skeletal survey has been replaced by whole body CT, whole body MRI (WB-MRI) and [18F]FDG-PET/CT for the detection of bone marrow lesions and less frequent extramedullary plasmacytomas.Beyond diagnosis, imaging methods are expected to provide the clinician with evaluation of the response to treatment. Imaging techniques are consistently challenged as treatments become more and more efficient, inducing profound response, with more subtle residual disease. WB-MRI and FDG-PET/CT are the methods of choice to address these challenges, being able to assess disease progression or response and to detect “minimal” residual disease, providing key prognostic information and guiding necessary change of treatment.This paper provides an up-to-date overview of the WB-MRI and PET/CT techniques, their observations in responsive and progressive disease and their role and limitations in capturing minimal residual disease. It reviews trials assessing these techniques for response evaluation, points out the limited comparisons between both methods and highlights their complementarity with most recent molecular methods (next-generation flow cytometry, next-generation sequencing) to detect minimal residual disease. It underlines the important role of PET/MRI technology as a research tool to compare the effectiveness and complementarity of both methods to address the key clinical questions.

Download Full-text

Comparison of the diagnostic performance and impact on management of 18F-FDG PET/CT and whole-body MRI in multiple myeloma

European Journal of Nuclear Medicine and Molecular Imaging ◽

10.1007/s00259-020-05182-2 ◽

2021 ◽

Author(s):

Olwen Westerland ◽

◽

Ashik Amlani ◽

Christian Kelly-Morland ◽

Michal Fraczek ◽

...

Keyword(s):

Multiple Myeloma ◽

Clinical Data ◽

Bone Disease ◽

Fdg Pet ◽

Diagnostic Performance ◽

Whole Body ◽

Bone Lesions ◽

Pet Ct ◽

18F Fdg ◽

Fdg Pet Ct

Abstract Purpose Comparative data on the impact of imaging on management is lacking for multiple myeloma. This study compared the diagnostic performance and impact on management of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and whole-body magnetic resonance imaging (WBMRI) in treatment-naive myeloma. Methods Forty-six patients undergoing 18F-FDG PET/CT and WBMRI were reviewed by a nuclear medicine physician and radiologist, respectively, for the presence of myeloma bone disease. Blinded clinical and imaging data were reviewed by two haematologists in consensus and management recorded following clinical data ± 18F-FDG PET/CT or WBMRI. Bone disease was defined using International Myeloma Working Group (IMWG) criteria and a clinical reference standard. Per-patient sensitivity for lesion detection was established. McNemar test compared management based on clinical assessment ± 18F-FDG PET/CT or WBMRI. Results Sensitivity for bone lesions was 69.6% (32/46) for 18F-FDG PET/CT (54.3% (25/46) for PET component alone) and 91.3% (42/46) for WBMRI. 27/46 (58.7%) of cases were concordant. In 19/46 patients (41.3%) WBMRI detected more focal bone lesions than 18F-FDG PET/CT. Based on clinical data alone, 32/46 (69.6%) patients would have been treated. Addition of 18F-FDG PET/CT to clinical data increased this to 40/46 (87.0%) patients (p = 0.02); and WBMRI to clinical data to 43/46 (93.5%) patients (p = 0.002). The difference in treatment decisions was not statistically significant between 18F-FDG PET/CT and WBMRI (p = 0.08). Conclusion Compared to 18F-FDG PET/CT, WBMRI had a higher per patient sensitivity for bone disease. However, treatment decisions were not statistically different and either modality would be appropriate in initial staging, depending on local availability and expertise.

Download Full-text

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

International Journal of Molecular Sciences ◽

10.3390/ijms21155406 ◽

2020 ◽

Vol 21 (15) ◽

pp. 5406 ◽

Cited By ~ 1

Author(s):

Bastien Jamet ◽

Elena Zamagni ◽

Cristina Nanni ◽

Clément Bailly ◽

Thomas Carlier ◽

...

Keyword(s):

Multiple Myeloma ◽

Fdg Pet ◽

Metabolic Response ◽

Residual Disease ◽

Complete Response ◽

Therapeutic Assessment ◽

Complete Metabolic Response ◽

Pet Ct ◽

Fdg Pet Ct ◽

Minimal Residual

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.

Download Full-text

Imaging of Monoclonal Gammapathy of Undetermined Significance and Smoldering Multiple Myeloma

Cancers ◽

10.3390/cancers12020486 ◽

2020 ◽

Vol 12 (2) ◽

pp. 486 ◽

Cited By ~ 2

Author(s):

Bastien Jamet ◽

Clément Bailly ◽

Thomas Carlier ◽

Cyrille Touzeau ◽

Anne-Victoire Michaud ◽

...

Keyword(s):

Computed Tomography ◽

Multiple Myeloma ◽

Fdg Pet ◽

Whole Body ◽

Bone Lesions ◽

Rapid Progression ◽

Smoldering Multiple Myeloma ◽

Pet Ct ◽

Fdg Pet Ct ◽

Undetermined Significance

Multiple myeloma (MM) is always preceded by an initial monoclonal gammopathy of undetermined significance (MGUS) that then develops into asymptomatic or smoldering multiple myeloma (SMM), which constitutes an intermediate clinical stage between MGUS and MM. According to a recent study, risk factors for faster MGUS to MM progression include an M protein of 1.5 g/dL or more and an abnormal free light chain ratio in patients with non-IgM MGUS. Therefore, the International Myeloma Working Group (IMWG) decided to recommend whole-body computed tomography (WBCT) for patients with high-risk MGUS in order to exclude early bone destruction. Studies evaluating magnetic resonance imaging (MRI) in SMM found an optimal cutoff of two or more focal lesions to be of prognostic significance for fast progression into symptomatic disease and considered this biomarker as a myeloma-defining event (MDE) needing to start therapy with the aim to avoid progression to harmful bone lesions. Moreover, studies assessing positron emission tomography (PET) with computed tomography (CT) using 18F-deoxyglucose (FDG) (FDG-PET/CT) in SMM showed that presence of focal bone lesion without underlying osteolysis is associated with a rapid progression to symptomatic MM. Latest IMWG guidelines recommended to perform WBCT (either CT alone or as part of an FDG-PET/CT protocol) as the first imaging technique at suspected SMM and, if these images are negative or inconclusive, to perform whole-body MRI. The goal of this paper is to clarify the role of different imaging modalities in MGUS and SMM workups.

Download Full-text

A prospective study comparing whole-body skeletal X-ray survey with 18F-FDG-PET/CT, 18F-NaF-PET/CT and whole-body MRI in the detection of bone lesions in multiple myeloma patients

Acta Radiologica Open ◽

10.1177/2058460117738809 ◽

2017 ◽

Vol 6 (10) ◽

pp. 205846011773880 ◽

Cited By ~ 5

Author(s):

Eva Dyrberg ◽

Helle W. Hendel ◽

Gina Al-Farra ◽

Lone Balding ◽

Vibeke B. Løgager ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Disease ◽

Fdg Pet ◽

Imaging Techniques ◽

Whole Body ◽

Bone Lesions ◽

X Ray ◽

Body Regions ◽

Pet Ct ◽

Fdg Pet Ct

Background For decades, the most widely used imaging technique for myeloma bone lesions has been a whole-body skeletal X-ray survey (WBXR), but newer promising imaging techniques are evolving. Purpose To compare WBXR with the advanced imaging techniques 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT), 18F-sodium fluoride (NaF) PET/CT and whole-body magnetic resonance imaging (WB-MRI) in the detection of myeloma bone lesions. Material and Methods Fourteen patients with newly diagnosed multiple myeloma were prospectively enrolled. In addition to WBXR, all patients underwent FDG-PET/CT, NaF-PET/CT, and WB-MRI. Experienced specialists performed blinded readings based on predefined anatomical regions and diagnostic criteria. Results In a region-based analysis, a two-sided ANOVA test showed that the extent of detected skeletal disease depends on the scanning technique ( P < 0.0001). Tukey’s multiple comparison test revealed that WB-MRI on average detects significantly more affected regions than WBXR ( P < 0.005), FDG-PET/CT ( P < 0.0001), and NaF-PET/CT ( P < 0.05). In a patient-based analysis, a Cochran’s Q test showed that there are no significant differences in the proportion of patients with bone disease detected by the different scanning techniques ( P = 0.23). Determination of intrareader variability resulted in Kappa coefficients corresponding to moderate (FDG-PET/CT) and substantial agreement (WB-MRI, WBXR, NaF-PET/CT). Conclusion WB-MRI detects on average significantly more body regions indicative of myeloma bone disease compared to WBXR, FDG-PET/CT, and NaF-PET/CT. The lack of significance in the patient-based analysis is most likely due to the small number of study participants.

Download Full-text

P-011: 18F-FDG PET/MRI for imaging minimal residual disease evaluation in Multiple Myeloma

Clinical Lymphoma Myeloma & Leukemia ◽

10.1016/s2152-2650(21)02145-5 ◽

2021 ◽

Vol 21 ◽

pp. S45

Author(s):

Gregorio Barilà ◽

Filippo Crimi’ ◽

Susanna Vedovato ◽

Massimiliano Arangio Febbo ◽

Antonio Maroccia ◽

...

Keyword(s):

Multiple Myeloma ◽

Minimal Residual Disease ◽

Fdg Pet ◽

Residual Disease ◽

18F Fdg ◽

Minimal Residual

Download Full-text

Minimal residual disease in multiple myeloma: an important tool in clinical trials

Reviews on Recent Clinical Trials ◽

10.2174/1574887116666211123092915 ◽

2021 ◽

Vol 16 ◽

Author(s):

Alessandro Gozzetti ◽

Monica Bocchia

Keyword(s):

Multiple Myeloma ◽

Clinical Trials ◽

Minimal Residual Disease ◽

Residual Disease ◽

New Drugs ◽

Next Generation ◽

Depth Of Response ◽

Next Generation Sequencing Ngs ◽

Future Therapy ◽

Minimal Residual

: Minimal residual disease (MRD) detection represents a great advancement in multiple myeloma. New drugs are now available that increase depth of response. The International Myeloma Working Group recommends the use of next-generation flow cytometry (NGF) or next-generation sequencing (NGS) to search for MRD in clinical trials. Best sensitivity thresholds have to be confirmed, as well as timing to detect it. MRD has proven as the best prognosticator in many trials and promises to enter also in clinical practice to guide future therapy.

Download Full-text