OAB-060: Prospective comparison of contemporary whole body MRI and FDG PET/CT for disease detection and correlation with markers of disease burden in myeloma: results of the iTIMM trial

Abstract

<h3>Background</h3> Sensitive detection of bone marrow disease and stratified patient management according to clinical risk can confer survival advantages in multiple myeloma (MM). Recent international guidelines include whole body MRI (WB MRI) and Fluorodeoxyglucose (FDG) PET/CT for bone marrow disease imaging in patients with a suspected diagnosis of MM. However, prospective studies comparing detection of MM by contemporary WB MRI as per MY-RADS consensus against FDG PET/CT are few. We report here on protocol-defined endpoints of the iTIMM (NCT02403102) study, which compared WB MRI and PET/CT, their relationship with serum and bone marrow estimates of disease burden, as well as molecular tumor characteristics. <h3>Methods</h3> The iTIMM study enrolled patients with newly diagnosed MM or at first relapse, planned to receive autologous stem cell transplantation. Matched baseline diffusion weighted and Dixon 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. 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. <h3>Results</h3> Sixty patients (35 male; mean age 60 years) were enrolled between May 2015 and March 2018 and underwent paired baseline WB MRI as per MY-RADS 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, including Holm's correction for multiplicity) for long bones, lumbar spine and pelvis. Four patients in our study showed two or more focal lesions ≥5 mm only on WB MRI but not FDG PET/CT. All lesions detected by WB MRI but not PET/CT were resolving in follow-up scans after treatment, excluding false positives. In 49/60 (81.7%) patients, WB MRI detected diffuse disease, compared to 10/60 (16.7%) by FDG PET-CT; WB MRI was more sensitive across all anatomical areas (P<0.05 (Holm's)). All patients without focal disease presented diffuse disease on WB MRI (n=10). Bone marrow plasma cell infiltration and serum paraprotein levels were significantly higher for patients with diffuse disease on WB MRI, but not PET/CT. All genetically high-risk tumors, defined by t(4;14), t(14;16), del(1p), gain(1q) or del(17p), showed diffuse infiltration on WB MRI. <h3>Conclusions</h3> Contemporary WB MRI is more sensitive regarding detection of focal and diffuse disease compared with FDG PET/CT; together with its capability to assess response proposing it as a standard for tumor imaging in MM. In addition, measurability of diffuse disease and its association with higher disease burden and high-risk molecular profiles supports WB MRI radiomic biomarker development.