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Simple Summary: Smoldering multiple myeloma is a heterogenous precursor state of multiple myeloma—both the time until progression and the cause of progression vary within this subgroup. While the number of focal lesions in whole-body MRI (magnetic resonance imaging) is known to be of prognostic value, we investigated whether additional parameters like the size or growth dynamics of focal lesions or precisely quantified diffuse infiltration are connected to risk and cause of progression. We found that both the size and dynamics of focal lesions correlate with progression to multiple myeloma and with existence/appearance of corresponding osteolytic lesions in near-term computed tomography (CT) scans. Furthermore, a score combining intensity and extent of diffuse infiltration showed connections with risk of progression and decrease in hemoglobin. We conclude that these parameters from whole-body MRI can help to predict the clinical course of disease in smoldering multiple myeloma (SMM) patients, with implications for diagnostic follow-up and possibly more specified therapeutic approaches in the future. The purpose of this study was to analyze size and growth dynamics of focal lesions (FL) as well as to quantify diffuse infiltration (DI) in untreated smoldering multiple myeloma (SMM) patients and correlate those MRI features with timepoint and cause of progression. We investigated 199 whole-body magnetic resonance imaging (wb-MRI) scans originating from longitudinal imaging of 60 SMM patients and 39 computed tomography (CT) scans for corresponding osteolytic lesions (OL) in 17 patients. All FLs >5 mm were manually segmented to quantify volume and growth dynamics, and DI was scored, rating four compartments separately in T1- and fat-saturated T2-weighted images. The majority of patients with at least two FLs showed substantial spatial heterogeneity in growth dynamics. The volume of the largest FL (p = 0.001, c-index 0.72), the speed of growth of the fastest growing FL (p = 0.003, c-index 0.75), the DI score (DIS, p = 0.014, c-index 0.67), and its dynamic over time (DIS dynamic, p < 0.001, c-index 0.67) all significantly correlated with the time to progression. Size and growth dynamics of FLs correlated significantly with presence/appearance of OL in CT within 2 years after the respective MRI assessment (p = 0.016 and p = 0.022). DIS correlated with decrease of hemoglobin (p < 0.001). In conclusion, size and growth dynamics of FLs correlate with prognosis and local bone destruction. Connections between MRI findings and progression patterns (fast growing FL—OL; DIS—hemoglobin decrease) might enable more precise diagnostic and therapeutic approaches for SMM patients in the future. [ABSTRACT FROM AUTHOR]

Simple Summary: According to the current SLiM-CRAB-criteria, asymptomatic multiple myeloma patients who show >1 focal lesion in MRI are now upstaged to multiple myeloma with treatment indication. While the anatomic coverage of MRI protocols differs from spine over spine plus pelvis to whole-body between different institutions, the cutoff for the number of focal lesions which is currently used for the staging decision is not adapted according to the protocol. We found that usage of different MRI protocols leads to markedly different staging decisions according to current SLiM-CRAB-criteria. Adapting the cutoff for the number of focal lesions according to the MRI protocol enables to select comparable risk groups when using different MRI protocols. The combination of >3FL in spine and pelvis or >4FLs in the whole body came closest to select patients with an 80% probability to develop CRAB-criteria within 2 years, which was the original goal of the IMWG. The purpose of this study was to assess how different MRI protocols (spinal vs. spinal plus pelvic vs. whole-body (wb)-MRI) affect staging in patients with smoldering multiple myeloma (SMM), according to the SLiM-CRAB-criterion '>1 focal lesion (FL) in MRI'. In this retrospective study, a baseline cohort of 147 SMM patients with wb-MRI at initial diagnosis was investigated, including prognostic data regarding development of CRAB-criteria. Fifty-two patients formed a follow-up cohort with a median of three wb-MRIs. The locations of all FLs were determined and it was calculated how staging decisions regarding the criterion '>1 FL in MRI' would have been made if only a limited anatomic area (spine vs. spine plus pelvis) would have been covered by the MRI protocol. Furthermore, subgroups of patients selected by different cutoff-protocol-combinations were compared regarding their prognosis for development of CRAB-criteria. With an MRI protocol limited to spine/spine plus pelvis, only 28%/64% of patients who actually had >1 FL in wb-MRI would have been rated correctly as having '>1 FL in MRI'. Fifty-four percent/36% of patients with exactly 1 FL in spine/spine plus pelvis revealed >1 FL when the entire wb-MRI was analyzed. During follow-up, four more patients developed >1 FL in wb-MRI; both limited MRI protocols would have detected only one of these four patients as having >1 FL at the correct timepoint. Having >1 FL in spine/in spine plus pelvis/in the whole body was associated with a 43%/57%/49% probability of developing CRAB-criteria within 2 years. Patients with >3 FL in spine plus pelvis and patients with >4 FL in the whole body had an 80% probability to develop CRAB-criteria within 2 years. MRI protocols limited to the spine or to spine plus pelvis lead to substantial underdiagnoses of patients who actually have >1 FL in wb-MRI at baseline and during follow-up, which influences staging and treatment decisions according to the current SLiM-CRAB criteria. However, given the spatial distribution of FLs and the analysis on clinical course of patients indicates that the cutoff for the number of FLs should be adopted according to the MRI protocol when using MRI for staging in SMM. [ABSTRACT FROM AUTHOR]