1. Yale University School of Medicine
Whole Body Magnetic Resonance Imaging in Newly Diagnosed Multiple Myeloma: Influence on Treatment Decisions
Natalia Neparidze, MD
Assistant Professor
Section of Hematology
Yale Cancer Center
Yale University School of Medicine

2. Introduction Historically metastatic bone survey (MBS)
standard radiographic test in multiple myeloma (MM)
Limitations: lack of sensitivity
Advanced imaging (MRI, or PET) more sensitive
Reserved for select cases:
Asymptomatic MM
Plasmacytoma
Patients with bone pain
Compression fractures
Focal neurologic deficit

3. Advanced Imaging for Evaluation of MM
Meta-analysis
comparison:
MRI
PET-CT CT
Met Bone survey
Up to 80% more lesions were detected by newer imaging techniques: MRI, PET, PET-CT when compared to bone survey
Lesions detected by CT or MBS
Lesions detected by MRI or PET
Regelink Brit J Hematol 2013

4. MRI for Evaluation of Myeloma
MRI detects focal lesions in 52% of pts w negative MBS
Advantages
Discrimination of NL and invaded BM
Detection of extramedullary dz
Evaluation of cord involvement
Better sensitivity for lytic bone lesions
Walker et al 2007

5. MRI Patterns of Marrow Involvement
Five MRI patterns
Focal
Diffuse
Combined diffuse and focal
Normal BM
Variegated or “salt and pepper”
Terpos JCO 2011; Dimopoulos JCO 2015

6. Superiority of Whole Body MRI (WB-MRI)
Paired scans PET and WB-MRI
WB-MRI detects higher burden of MM than PET
Increased ability to detect diffuse BM dz
WB-MRI outperforms PET in the assessment of disease infiltration in iliac bones
MRI should be the investigation of choice for detection of myeloma marrow infiltration
Pawlyn et al ASH 2015; Leukemia 2016
WB-MRI fat fraction change at 8 wks of induction differentiates responders from non-responders
early response and predictive imaging biomarker. Latifoltojar et al ASH 2015

7. MRI in Asymptomatic Multiple Myeloma (AMM)
MRI as a prognostic biomarker
SWOG S010 study- detection of multiple focal lesions on MRI increased risk of progression
Abnormal signal on MRI associated with very high risk of AMM progression
More than one lesion >5 mm –considered symptomatic disease  require therapy
Dhodapkar 2014; Dimopoulos et al, 2015; Kastritis 2013

8. MRI in Asymptomatic Myeloma
IMWG recommends WB-MR for:
All patients w suspected AMM
Solitary bone plasmacytoma
Ideally WB-MRI
MRI of total spine and pelvis when WB-MRI not available
(50% lesions will be missed by imaging spine alone)
Disadvantage of standard protocols of MRI :
Prolonged acquisition time
Difficult to perform in ill pts
Claustrophobic pts
Dimopoulos 2015; Bauerle 2009)

9. WB-MRI at Yale Need to advance newer methodologies / optimal imaging
WB-MRI at YNHH
Acquisition time 40 minutes
Highly experienced musculoskeletal MRI radiologists
Highly skilled in targeted bone biopsies /soft tissue biopsies
Physicians at the Department of Radiology, performing MRI and image-guided biopsies:
Elliott Brown, MD
Andrew Haims, MD
Andrew Lischuk, MD
Jeffrey Weinreb, MD

10. Study Rational
We predict that WB-MRI will outperform standard imaging in initial evaluation of MM and will influence treatment decisions
Baseline MBS and WB-MRI were performed on newly diagnosed MM patients prior to initiation of therapy
Multi-planar, multi-sequence WB-MRI was acquired without IV contrast
The imaging studies were evaluated to determine their respective merits for disease staging and their impact on treatment decisions

11. Study Design New Diagnosis of MM Standard evaluation Bone survey and
WB-MRI
Images reviewed
by musculoskeletal
Radiology group
Impact on staging and
on treatment decisions
was evaluated

12. Results WB-MRI detected MM lesions in 33% of pts (5/15)
MBS detected lesions in only 6% (1/15)
WB-MRI influenced staging in 73% of pts (11/15)
WB-MRI impacted treatment decisions in 46% of pts (7/15)
MBS missed MM lesions in 27% of pts (4/15)
MM bone lesions occurred in the axial skeleton, mostly cervical, thoracic, lumbar spine and pelvis

13. Results
MM Lesion Detection
Test Characteristics
% Patients

14. Conclusion
WB-MRI at diagnosis provides valuable information on the extent and the stage of the disease, significantly influences treatment decisions and is worth to be incorporated in initial diagnostic evaluation of patients with multiple myeloma.

15. Ongoing Efforts Prognostic significance of MRI
Diffuse MRI pattern correlates with:
High risk cytogenetics
Advance ISS stage
Increased angiogenesis
Poorer OS
Despite prognostic significance no treatment has been suggested for pts with high risk MRI pattern

16. Ongoing Efforts Role of MRI in follow-up
Limited data on value of imaging during treatment and follow-up
IMWG recs- no suggested imaging in responding patients
MRI to be included in future
for routine staging, prognosis
and response assessment
(resolution or decrease in focal
lesions)
? Timing, frequency of follow-up
Accuracy, spec/sens of response,
False positive results
Hillengass Hematologica 2012, Bannas Eur Rad 2012
Walker et al JCO 2007

17. Response Criteria

18. Incorporation of MRI in Lesion Response Assessment
Imaging-defined Myeloma Lesion Response Criteria
MRI-defined Complete response: 
Resolution of bone or extramedullary focal MM lesions, normalization of diffuse marrow signal
MRI-defined Partial response: 
Decrease in size and number of bone or extramedullary MM lesions

19. Novel MRI Techniques Dynamic contrast-enhanced MRI
Provides data on microcirculation
Microvascular density in BM
PET/MRI – novel modality
Both potentially valuable before and after treatment
Further studies are needed

20. Summary
WB-MRI is included in initial imaging for MM, especially valuable in asymptomatic stage
WB-MRI superior in assessing BM and overall disease burden
Valuable in staging, prognosis, influences treatment decisions
To be incorporated in future response assessment

21. Thank you
Acknowledgements: Yale Myeloma Team Madhav Dhodapkar, MD Stuart Seropian, MD Terri Parker, MD Noffar Bar, MD Tara Anderson, MD Diane Dirzius, RN
Yale MRI Radiology
Elliott Brown, MD
Andrew Haims, MD
Andrew Lischuk, MD
Jeffrey Weinreb, MD