Determining the Extent of Disease with Magnetic Resonance Imaging of the Bone Marrow (BM-MRI) in Patients with Multiple Myeloma (MM).
Authors: Ailawadhi Sikander , Derby Lyudmyla , Mashtare Terry L. , Miller Kena C. , Wilding Gregory , Padmanabhan Swaminathan , Gottlieb Ronald , Alberico Ronald A. , Klippenstein Donald L. , Abdelhalim Ahmed N. , Chanan-Khan Asher A. 
Published: April 2020

Abstract
Background: MM remains an incurable cancer. Treatment is often initiated with progressive increase in tumor burden and clinical symptoms. Tumor burden assessment is commonly done by disease stage, presence of lytic bone disease and beta-2 microglobulin (B2M). We investigated bone marrow imaging as a novel approach to quantify disease burden. In a separate report, we observed that MRI is more sensitive than BM aspirate/biopsy (BM-Bx) for assessing extent of marrow involvement in MM patients. In this study we validate that extent of marrow disease detected by BM-MRI correlates with the clinical stage, presence of lytic bone lesions, B2M and secretor vs. non-secretor status of MM patients.
Methods: Extent of marrow involvement as evaluated by BM-MRI included sagittal T1 and fast spin echo inversion recovery sequences of the cervical, thoracic and lumbosacral spine and coronal T1 and fast spin echo inversion recovery sequences of the sacrum and pelvic bones. Clinical staging was done as per Durie-Salmon (DS) and the International Staging System (ISS) while lytic bone lesions were assessed by skeletal radiographs. Secretory MM was identified by presence of M-protein in serum or urine by electrophoresis. To study the statistical relationship between pairs of ordinal variables the test corresponding to the Spearman correlation was used and statistical relationship between nominal and ordinal variables was determined by the Wilcoxon or Kruskal-Wallis test. A 0.05 nominal significance level was used in all testing. Following staging system was defined for evaluation of the marrow involvement by BM-MRI: A (0%), B (&lt; 10%), C (10%–25%), D (26%–50%), E (&gt; 50%).
Results: We evaluated 170 consecutive patients (77 females and 93 males). Median age was 61 years (range 35–83). Advance stage disease (&gt; stage 1) based on DS or the ISS criteria was observed in 47.6% (n=81) and 53.3% (n=77) patients, respectively. Lytic lesions were noted in 70.6% (n=120) patients and secretory disease in 85.9% (n=146) patients. Estimated Spearman correlation coefficient between BM-MRI involvement and DS stage was 0.2795 (p = 0.0006; 95% CI 0.1222, 0.4368) demonstrating a significant association between BM-MRI involvement and DS stage. This correlation with clinical stage remained significant using the ISS system (p = 0.0001). The correlation of marrow infiltration on BM-MRI was also significantly associated with the presence of lytic bone disease (p&lt;0.0001) as well as the B2M levels (p&lt;0.0001). There was no significant association between MRI involvement and patient age (p = 0.7921) or the Ig type (p=0.8123). Interestingly, marrow involvement on BM-MRI had a significant association with secretor-status of the patients (p=0.0081).
Conclusions: BM-MRI is novel approach to quantify disease burden in patients with MM. Our investigation in a large cohort of patients demonstrates that the extent of marrow involvement determined by this method correlates accurately with other conventional methods used to assess myeloma disease burden such as clinical stage, lytic bone disease or B2M. We therefore conclude that BM-MRI can be routinely used to determine disease burden in patients with multiple and can be effectively employed in monitoring response to therapy.