Multiple Myeloma and Smoldering Myeloma: Prospective Evaluation of 3 T Whole Body MRI and 18F-FDG PET/CT and Their Impact on Clinical Management
Authors: Cerchione Claudio , Bezzi Davide , Nappi Davide , Marchesini Matteo , Prochowski Iamurri Andrea , Caroli Paola , Cattabriga Arrigo , Cangini Delia , Feliciani Giacomo , Loi Emiliano , Matteucci Federica , Barone Domenico , Ronconi Sonia , Ceccolini Michela , Musuraca Gerardo , Normanno Nicola , Martinelli Giovanni , Rossi Alice 
Published: December 2024

Background: 18F-fluorodeoxyglucose (FDG) PET with CT (FDG-PET/TC) and magnetic resonance imaging (MRI) are both imaging diagnostic tools adopted in diagnosis and/or response assessment in multiple myeloma (MM). As 2016 IMWG criteria state that detection of bone lesions is essential for diagnosis of MM (especially when CT is negative) and/or for ruling out them in patients with high risk smoldering MM and a PET/TC is one of the techniques essential for detecting the presence of bone disease in the diagnosis of MM. MR is the major diagnostic tool for identifying extra- or para-skeletal manifestations and complications, namely pathological fractures and spinal cord compression. Both techniques can be useful in newly diagnosed MM as well in relapsed setting.

Aims: To evaluate diagnostic accuracy of Whole body-MRI (WB-MRI) and fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT (PET/CT) in the detection of bone focal lesions (FLs) and of bone marrow infiltration (BMI) in Multiple Myeloma and high-risk Smoldering Myeloma (HR-SMM); to evaluate their clinical relevance in the patient management.

Methods: From January 2021 to January 2024, we enrolled into an observational prospective trial 98 consecutive patients affected by Multiple Myeloma (54Male; mean age, 67 years ± 10 [SD]) divided into 3 groups of patients; 37 had a newly diagnosed MM according to the IMWG (group 1); 37 were in follow-up after autologous stem cell transplantation with clinical or laboratorist data suspicious for relapse or progression (group 2)and 24 were affected by relapsed/refractory MM during treatment (group 3). In addition we enrolled 39 patients newly diagnosed high risk SMM, according to IMWG (19 Male, mean age 59 years+-10 [SD]). Clinico-laboratoristic data, WB-MRI (According to Myeloma Response Assessment and Diagnosis System, My-RADS criteria) and PET/CT (According to Italian Myeloma criteria for Pet Use: IMPeTUs) were performed in combination within 1 month from each other; 2 double- blinded specialist readers evaluated bone lesions (per-patients, per-pattern of FLs and BMI infiltration basis) in each imaging method. Diagnosis was performed by International Myeloma Working Group (IMWG) criteria as reference standard.

Results: on a per-patien basis, 89/98 patients (90%) had concordant PET/CT and WB-MRI scans, while 9/89 (10%) had discordant scans in terms of positivity/negativity. Among concordant studies, 30/89 (34%) patients were negative with both imaging methods while 59/89 (66%) were positive at both (including FLs and/or BMI). Among discordant studies, 8/9 patients had a positive WB-MRI scan and a negative PET-CT scan (6 cases with BMI or micronodular involvement alone), whereas 1/9 had a positive PET-CT and a negative WB-MRI. PET/CT detected FLs pattern in 55/98 patients, WB-MRI alone identified FLs pattern in 3 patients (58/98). PET-CT led to a change of treatment approach in 51/98 patients (52%), WB-MRI in 59/98 patients (60%), the combination of the two methods led to a change of management in 61/98 (62%), highlighted in the case of suspected post-transplant relapse ( 13 change of treatment with both methods, 11 with PET-CT and 10 with WB-MRI). Furthemore, WB-MRI led to a change of management for incidental findings in additional 5 patients (4 suspected malignancies and 1 spinal cord compression). Interim analysis in HR- SMM showed discordance between the results of the two imaging modalities in 8/35 (23%). WB-MRI detected BMI pattern without any overt focal lesion in 5 patients (only 1 correlated with PET/CT) and FLs pattern in 5 patients (2 confirmed also in PET/CT), while PET/CT detected an additional FLs pattern in 1 patient, without bone lytic lesion evidence at the CT images. Both methods led to 3 changes of management, whereas MRI alone led to a change of tratment approach in 4 patients (10%), 3 diagnoses and 1 accessory finding of suspected cholangiocarcinoma.

Summary/Conclusions: Our preliminary data underlines the fundamental role of functional imaging in the evaluation of FLs and BMI in MM with a superior detection rate of WB-MRI related to the ability to identify diffuse and micronodular pattern. A potential complementary role of the two methods in che clinical management could be suggested in suspicion of relapsed or progressing MM. Furthemore our prospective trial supports the utmost role of WB-MRI (performed according to MY-RADS) in the assessment of patients affected by high risk Smoldering Myeloma.