Prognostic Significance Of Parameters Of Dynamic Contrast-Enhanced MRI Detecting Increased Bone Marrow Microcirculation In Monoclonal Plasma Cell Disorders
Authors: Hillengass Jens , Ritsch Judith , Merz Maximilian , Goldschmidt Hartmut , Kunz Christina , Wagner-Gund Barbara , Ho Anthony , Moehler Thomas M. , Delorme Stefan 
Published: October 2019

Abstract

Introduction
Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) is a non-invasive imaging technique allowing the detection of changes in local microcirculation reflecting increased angiogenesis. DCE-MRI parameters Amplitude A (reflecting blood volume) and exchange rate constant kep (reflecting vascular permeability) are increased in bone marrow exams of patients with active multiple myeloma (MM) compared to healthy controls. In the current prospective study we analyzed the prognostic significance of the DCE-MRI parameters in 289 patients with monoclonal plasma cell disorders and 33 healthy controls.

Methods
The patient group consisted of 68 individuals with monoclonal gammopathy of undetermined significance (MGUS), 90 patients with smoldering MM (sMM) and 131 patients with symptomatic MM according to IMWG criteria. All patients and controls underwent standardized DCE-MRI with high temporal resolution (T1w-turboFLASH) of the lumbar spine (symptomatic patients before start of therapy). Regions of interest were drawn manually on T1-weighted images encompassing the bone marrow of each of the 5 lumbar vertebrae sparing the vertebral vessel. Values of the DCE-MRI parameters of the 5 lumbar vertebrae were summarized per patient in median values. Log transformation was used for median kep values.

Results
Significant differences in Amplitude A were found between sMM and controls (P=0.004), sMM and MGUS (P=0.01), and MM and all other groups (P<0.001 respectively). For exchange rate constant kep differences were significant between sMM and controls (P=0.01), sMM and MGUS (P=0.01) and MM and all other groups (P<0.001 respectively). P-values were adjusted for multiple testing by Holm's method. Comparison of DCE-MRI- and clinical parameters revealed a significant positive correlation of Amplitude A with beta2-microglobulin (P<0.001), high risk cytogenetics (P=0.009), immunoparesis (P<0.001) and a negative correlation with albumin, hemoglobin and age (P<0.001, respectively). For exchange rate constant kep the following significant correlation were found: positive correlation with beta2-microglobulin (P<0.001), LDH (P=0.03), immunoparesis (P<0.001) and negative correlation with albumin (P=0.03), hemoglobin (P<0.001) and age (P=0.03). Application of univariate and multivariate Cox models revealed a significant prognostic impact for median of DCE-MRI parameter Amplitude A for progression free survival of patients with MGUS (univariate P=0.02), sMM (univariate P=0.002; multivariate P=0.03) and for overall survival of MM patients (multivariate P=0.05). Log transformed arameter kep showed prognostic significance for PFS of MM patients (univariate P=0.04). The multivariate Cox model was adjusted for the following additional factors: plasma cells in bone marrow, M-Protein, IgG-subtype, presence of immunoparesis and age. M-protein (P=0.004), age (P=0.03) and a non-IgG-type (P=0.006) also were revealed as significant prognostic factors.

Conclusion
DCE-MRI is a non-invasive imaging tool delivering parameters on bone marrow microcirculation which are correlated to clinical markers of disease activity as well stage of disease. In all groups of patients especially DCE-MRI parameter Amplitude A is of significant prognostic value for progression free and in symptomatic patients also for overall survival.

Disclosures:
No relevant conflicts of interest to declare.