UMHS-PUHSC JOINT INSTITUTE

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1 Imaging Biomarkers for Staging and Assessing Response to Therapy in Multiple Myeloma Qian Dong, MD. Radiology University of Michigan Wei Guo, MD. Orthopedic Oncology Peking University Second Hospital

2 Team Peking University Second Hospital Wei Guo, MD. Xiaodong Tang MD. Yi Yang MD. Tingting Ren PhD. University of Michigan Qian Dong, MD. Chuan Zhou, PhD. Daniel Couriel, MD. Craig Cole, MD.

3 Executive Summary Multiple myeloma (MM) is the 2nd most common hematologic malignancy affecting terminally differentiated plasma cells. Conventional radiological skeletal survey has been the imaging reference standard for decades, despite significant limitation. To optimize therapy for individual patients and improve the prognosis of patients with MM, there is a critical need to develop non-invasive imaging biomarkers.

4 Primary Aim: Specific Aims To investigate the ability of 3D dynamic intensity energy transformation (DIET) enhanced MRI and diffusionweighted MRI (DW-MRI) for assessing treatment response in multiple myeloma that correlates with clinical outcome, and compare it to conventional MRI. Secondary Aim: Establish to what extent DIET enhanced and diffusion MRI predict treatment response and survival in patients with multiple myeloma.

5 Long-term goal: Background To develop clinically-translatable MRI metrics to serve as prognostic and predictive biomarkers of treatment response in MM. We propose to evaluate the comparative effectiveness of a novel quantitative imaging measure versus standard of care imaging as prognostic biomarkers for treatment response in a prospective longitudinal bi-institutional cohort of patients. We will refine quantitative metrics to enhance conventional and functional MRI (DW-MRI).

6 Research Strategy & Methodology A total of 100 patients, 50 patients at each site will be enrolled Patients with newly diagnosed symptomatic multiple myeloma Baseline before treatment Induction treatment Computerized image analysis for response assessment Pre- and post-treatment spine MRI Lab test 2 or 3 months after treatment (Midpoint of induction treatment) T1, STIR, pre-and post- contrast sequences ADC calculation for DW-MRI 4 or 6 months after treatment (endpoint of induction treatment, pre- BMT) Feature extraction & selection Classifier & statistical analysis 7 or 9 months after treatment (3 months after BMT) Performance evaluation & comparison

7 Research Strategy & Methodology Time and Events Table Informed Consent T0: Baseline (pre-tx) X T1: 2 or 3 months after TX (midpoint of induction TX) T2: 4 or 6 months after TX (endpoint of induction TX, pre- BMT) T3: 7 or 9 months after TX (3 months after BMT) MRI X X X X Lab test X X X X Bone biopsy X X

8 Update and progress Protocol Review Committee (PRC) and IRB process After 2 presentations and 2 review cycles, the protocol was revised and approved from the Hematologic Malignancies-Bone Marrow Transplant program at University of Michigan The protocol was submitted to PRC, and is in the process of evaluation at University of Michigan Cancer Center Data collection and validation Optimize the total spine MRI protocol, obtained IRB approval for 10 normal volunteers 3 normal-volunteer scans. T1 and T2 weighted and diffusion MRI sequences have been finalized, and promising images are collected

9 Update and progress normal volunteer T1 T2 Diffusion -weighted

10 Update and progress Data collection and validation Retrospective data set: Increase from 29 patients to 64 patients: The agreement between DIET and clinical outcome reached: with a kappa value of Publications and presentations True Positive Fraction False Positive Fraction 1. Zhou C, Chan H-P, Dong Q, et al. Automated identification of spinal cord and vertebras on sagittal MRI. Proc SPIE, Medical Imaging: Computer-Aided Diagnosis. 2014;9035: Zhou C, Dong Q, Chan H-P, et al. Quantitative analysis of MRI for treatment response assessment of multiple myeloma (MM): stratification of MM infiltration pattern in bone marrow using dynamic intensity entropy transformation (DIET) method. 100th scientific assembly and annual meeting of Radiological Society of North America (RSNA). Chicago, IL: RSNA, 2014

11 Future directions & research plans Pending approval of PRC and IRB reviews Soon will start recruiting myeloma patients after PRC and IRB approval We believe that data from this research will lay the foundation for a larger scale clinical trial to definitively test the hypothesis, which will enable quantitative staging, treatment response monitoring, and prognosis prediction.

12 Thank You!