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.

Abstract

8012 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.

Impact of minimal residual disease standardised assessment by FDG-PET/CT in transplant-eligible patients with newly diagnosed multiple myeloma enrolled in the imaging sub-study of the FORTE trial

“… 31 However, it has not yet been possible to draw definitive conclusions on their use due to limited availability, the heterogeneity of specific tumour targets among the various patients, and the lack of prognostic data and standard reporting. Alternatively, other imaging techniques can be used, such as DWI-MRI, which has demonstrated high sensitivity, especially in detecting diffuse BM infiltration, showing significant changes in patients in remission after therapy, both early and at the end of the treatment 32 ; however, specificity problems are still unresolved. Recently, a group of expert radiologists, physicists and haematologists provided guidelines for the acquisition, interpretation, and reporting of DWI-MRI (MY-RADS imaging recommendations), to promote its standardisation and reduce the variability of interpretation between several studies.…”

“… 25 Validation of the MY-RADS criteria in prospective studies is on-going. 32 To date, homogeneous and prospective data on the comparison between DWI-MRI and FDG-PET/CT in the evaluation of response to therapy are lacking.…”

Development of machine learning support for reading whole body diffusion-weighted MRI (WB-MRI) in myeloma for the detection and quantification of the extent of disease before and after treatment (MALIMAR): protocol for a cross-sectional diagnostic test accuracy study

“…The scan population will comprise of; HV WB-MRI scans acquired from participants prospectively recruited from the sponsor site only (RMH), with the option of the Imperial Site providing previously acquired HV scans; WB-MRI scans acquired as part of clinical care from patients being managed at RMH and ICHT and WB-MRI scans previously acquired for a prospective research study in WB-MRI (iTIMM study) 9 19. All scans acquired for the study will be done, so using clinical standard of care trust protocols.…”

“…Scan and site-level data from these scans will be captured on case report forms (CRFs) for all cases in phases 1 and 2 and used as ‘ground truth’ in the classification of study output. Reference standard for phase 3 will be obtained from the source (iTIMM study) 19…”

“…Reference standard for phase 3 will be obtained from the source (iTIMM study). 19 Objectives Primary research objectives Phase 1: to develop a myeloma-specific ML algorithm to detect the presence of active disease on WB-MRI+ML (with machine learning '+ML') with sufficient sensitivity.…”