Whole Body Diffusion Weighted MRI (WB DWI) for the Management of Multiple Myeloma: High Concordance between MRI Diffuse Pattern and BONE Marrow Plasma CELL Infiltration RATE

Abstract

Background: Diffusion-weighted whole body MRI (WB-DWI) is a new functional imaging technique comprising anatomical and functional sequences with an emerging role in the management of multiple myeloma (MM) patients (pts) since it allows highly sensitive detection of diffuse bone marrow (BM) infiltration pattern and focal lesions, avoiding intravenous injections and radiation exposure. The aims of our study were 1) to test the correlation between plasma cells infiltration (BMPC) rate at BM biopsy and the presence of diffuse infiltration pattern at WB-DWI. 2) to compare response according to IMWG criteria and WB-DWI response and to establish the rate of discordancy (WB-DWI progression with increased focal lesions and at least a partial response according to IMWG criteria) Methods: We reviewed data regarding 45 MM patients (pts) observed in our Centre between September 2018 and July 2019 for whom quantification of serum and urine monoclonal component (MC), free light chains value (FLC), BM biopsy, whole body CT scan and WB-DWI data were available at the same time point. Sequential assessment of WB-DWI and laboratory data was available in 20 pts. Patients performed a WB-DWI (Magnetom Area, 1.5T, Siemens Enlarged Germany) for head to knee. The protocol included anatomical sequences T1 and T2 weighted with fat suppression on the sagittal plane specifically for the spine. Coronal T2 weighted fat suppression sequences are performed for the study of femural bone. Axial Dixon T1 weighted sequences of the whole scan region, in breath-old. The functional part is formed by diffusion weighted sequences in the axial plane. MM diagnosis and response were assessed by IMWG criteria. Response were categorized as follows: responsive patients if ≥PR, progressive disease if <PR. BM infiltration rate was used as a continuous variable. WB-DWI findings at first evaluation were categorized as follows: presence/absence of focal lesions, presence/absence of diffuse pattern of BM infiltration. Radiological re-assessment of both focal lesions and diffuse pattern was categorized as follows: reduced/stable/increased. Discordant pattern of progression was defined as: ≥PR + diffuse pattern stable/reduced + focal lesions increased. Association between two categorical variables was evaluated by Fisher's exact test. Mann-Whitney test was used to compare a quantitative variable among two independent groups of patients. P-values<0.05 were considered significant. Results: Table 1 summarizes the clinical and radiological data of the population on study. Median age was 64 years (range 38-86), median number of previous lines of therapy at time of evaluation was 0 (range 0-)2; 47% pts were at the onset, 31% were in follow-up after treatment completion, 22% had progressive disease. WB-DWI showed a diffuse pattern in 22 pts (49%); in 23 patients without a diffuse pattern, 7 (30%) had PBMC >10%; BMPC infiltration rate was significantly higher in pts with presence of diffuse pattern at WB-DWI (p<0.001; Figure 1). WB-DWI showed focal lesions in 35 pts (78%): 19 of them were at onset of disease. Most of the patients performing sequential assessment of WB-DWI were responsive according to IMWG criteria at time of WB-DWI re-evaluation (17 pts with ≥PR, 85%). Table 2 shows radiological findings according to IMWG response. Focusing on patients with ≥PR, WB-DWI diffuse pattern was reduced in 13 pts (76.5%) and stable in 4 pts (23.5%) with complete concordance between hematological and radiological findings (increased diffuse pattern in no pt with ≥PR); focal lesions were reduced in 76.5% and increased in 23.5%; a discordant pattern of progression was found in 4 patients (20%). Conclusions: Our study findsa significant correlation between presence of WB-DWI diffuse infiltration patter and BMPC rate, highlighting the possible future use of this radiological technique for monitoring BM residual disease. In addition, this study shows the possible not negligible emergence of discordant pattern of progression, probably deriving from the spatial heterogeneity of MM clones and their different sensitivity to therapy. Disclosures Mangiacavalli: celgene: Consultancy; Janssen cilag: Consultancy; Amgen: Consultancy. Varettoni:Gilead: Other: travel expenses; ABBVIE: Other: travel expenses; Roche: Consultancy; Janssen: Consultancy. Arcaini:Celgene: Speakers Bureau; Celgene, Roche, Janssen-Cilag, Gilead: Other: Travel expenses; Gilead Sciences: Research Funding; Bayer, Celgene, Gilead Sciences, Roche, Sandoz, Janssen-Cilag, VERASTEM: Consultancy.

The quantitative parameters based on marrow metabolism derived from synthetic MRI: A pilot study of prognostic value in participants with newly diagnosed multiple myeloma

“…The BMPC percentage is critical for MM diagnosis, assessment of treatment efficacy, and monitoring for recurrence 1 . The BMPC percentage was significantly correlated with tumor burden and prognosis in MM 26–28 . Beta‐2‐microglobulin, a low‐molecular weight protein expressed on the surface of almost all normal nucleated cells and many tumor cells, is a major serum biomarker of tumor burden in MM and a component of R‐ISS staging system 4,7,29,30 .…”

“…1 The BMPC percentage was significantly correlated with tumor burden and prognosis in MM. [26][27][28] Beta-2microglobulin, a low-molecular weight protein expressed on the surface of almost all normal nucleated cells and many tumor cells, is a major serum biomarker of tumor burden in MM and a component of R-ISS staging system. 4,7,29,30 In addition, the serum β 2 -microglobulin level was proved to be an independent predictor of survival in MM.…”

The Current Research Status of Imaging Assessment of Bone Disease in Multiple Myeloma

“…One of the key features of DW-MRI is its high sensitivity in detecting diffuse bone marrow infiltration and focal lesions, which are characteristic of MM. Studies have shown that DW-MRI can detect more focal lesions compared to conventional radiography and has a high concordance with the bone marrow plasma cell infiltration rate [36], [38]. Additionally, changes in ADC values post-treatment have been correlated with response to chemotherapy, with responders showing a significant increase in ADC values, indicating a reduction in cellularity and a positive treatment effect [39], [44].…”

“…The main advantage of DW-MRI is its ability to provide both anatomical and functional information about bone lesions without the need for ionizing radiation or intravenous contrast agents. This makes it particularly useful for patients who are unable to undergo contrast-enhanced studies or who require repeated imaging for monitoring disease progression or response to therapy [38]- [43].…”

Tumor Reduction in Multiple Myeloma: New Concepts for New Therapeutics

“…Other advances are also being implemented in the setting of imaging techniques. Whole-body diffusion-weighted MRI (WB-DWI) maintains the advantages of MRI to identify small lesions in bone marrow at diagnosis, but it also allows the quantification of residual disease through the apparent diffusion coefficient without the need for intravenous contrast and shows a good correlation with bone marrow infiltration, thus being superior to conventional MRI (91,92). Some preliminary studies have confirmed a benefit in PFS linked to the achievement of WB-DWI negativity after ASCT (93,94), additionally being a technique without ionizing radiation, which may overcome some of the limitations of PET-CT (95).…”