Personalized Medicine and Imaging Dynamic Contrast-EnhancedMagnetic Resonance Imaging for Assessment of Antiangiogenic Treatment Effects in Multiple Myeloma

Purpose: To noninvasively assess bone marrow microcirculation before and after therapy in patients with newly diagnosed multiple myeloma with dynamic contrast-enhanced MRI (DCE-MRI). Experimental Design: Ninety-six patients received DCE-MRI before and after primary treatment for newly diagnosed multiple myeloma. For the 91 evaluable patients, treatment consisted of high-dose therapy (HDT) with autologous stem cell transplantation (ASCT) in 82 patients and chemotherapy without ASCT in 9 patients. In addition, 33 healthy volunteers were imaged as the control group. Analysis of DCE-MRI was performed according to the two-compartment model by Brix to quantify amplitude A (associated with blood volume) and exchange rate constant kep (reflecting vessel permeability and perfusion). Results: Nonresponders showed significantly higher A-values before the start of therapy compared with responders (P 1⁄4 0.02). In both responders and nonresponders to therapy, A-values dropped significantly (P 1⁄4 0.004 and <0.001, respectively) after primary therapy, whereas lower values for kep were found only in responders (P < 0.001). Depth of remission was significantly correlated to decreased bone marrow microcirculation: Patients in near complete response (nCR) or complete remission (CR) after treatment showed significantly lower values for A compared with patients not achieving nCRþCR. The application of HDT or novel agents had no significant effect on DCE-MRI parameters after therapy, although patients treated with novel agents more often achieved nCRþCR (42%/12.5%; P < 0.002). Higher kep -values at secondMRI were positively correlated to shorter overall survival (HR 3.53; 95% confidence intervals, 1.21–10.33; P 1⁄4 0.02). Conclusion: Parameters from DCE-MRI are correlated to remission after primary therapy and outcome in newly diagnosed multiple myeloma. Clin Cancer Res; 1–7. 2014 AACR.