Prospective comparison of whole body MRI and FDG PET/CT for detection of multiple myeloma and correlation with markers of disease burden: Results of the iTIMM trial.
Authors: Kaiser Martin F. , Porta Nuria , Sharma Bhupinder , Levine Daniel , Koh Dow-Mu , Boyd Kevin , Pawlyn Charlotte , Riddell Angela M. , Downey Kate , Bonner Alison , Morgan Veronica A , Stern Simon , Jones Lydia , Cheung Betty , Kyriakou Charalampia , Kaczmarek Pawel , Winfield Jessica Mary , Blackledge Matthew D. , Oyen Wim J.G. , Messiou Christina 
Published: June 2021

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Background: Early and sensitive detection of bone marrow disease and stratified patient management according to clinical risk can confer survival advantages in multiple myeloma (MM). Whole body MRI (WB MRI) and Fluorodeoxyglucose (FDG) PET/CT are included in international guidelines for imaging in patients with a suspected diagnosis of MM. However prospective studies comparing detection of MM by contemporary WB MRI as per recent MY-RADS consensus against FDG PET/CT are lacking. We report here protocol-defined endpoints from the prospective iTIMM (NCT02403102) study, comparing WB MRI and PET/CT, their relationship with serum and bone marrow estimates of disease burden, as well as molecular tumor characteristics. Methods: Patients with newly diagnosed MM or at first relapse planned to receive chemotherapy and autologous stem cell transplantation were enrolled in iTIMM. Matched baseline WB MRI and FDG PET/CT were performed and baseline clinical data including tumor genetics collected. Scans were double reported for presence of focal and diffuse disease by expert MRI and PET/CT radiologists, blinded to each other’s assessment. Paired methods were used to compare burden and patterns of disease on WB MRI compared to FDG PET/CT at baseline. Primary and secondary trial endpoints include relationship between post-treatment WB MRI response and progression-free survival, for which follow-up is ongoing. Exploratory endpoints include comparison of baseline WB MRI and PET/CT and their correlation with laboratory parameters, for which data is complete and reported here. Results: From May 2015 to March 2018, sixty patients (35 male; mean age 60 years) underwent baseline WB MRI as per MY-RADS consensus and FDG PET/CT. At least one focal lesion was detected in 50/60 patients (83.3%) by WB MRI and in 36/60 patients (60%) by PET/CT. WB MRI was more sensitive ( P< 0.05) across anatomical regions except for ribs and cervical spine. Four patients in our study showed two or more focal lesions ≥5 mm only on WB MRI but not PET/CT. All lesions detected by WB MRI but not PET/CT resolved in follow-up scans after treatment, excluding false positives. In 49/60 (81.7%) patients, diffuse disease was detected by WB MRI, compared to 10/60 (16.7%) by PET-CT; WB MRI was more sensitive across all anatomical areas ( P< 0.05). Plasma cell infiltration and paraprotein levels were significantly higher for patients with diffuse disease on WB MRI, but not on PET/CT. All genetically high-risk tumours, defined by t(4;14), t(14;16), del(1p), gain(1q) or del(17p), showed diffuse infiltration on WB MRI. Conclusions: WB MRI increases detection of focal and diffuse disease compared with FDG PET/CT, including improved detection of focal lesions meeting criteria for active disease as per International Myeloma Working Group diagnostic criteria, proposing it as a gold standard for tumor imaging in MM. Clinical trial information: NCT02403102.