Magnetic Resonance Imaging (MRI) as part of Staging Work-Up for Newly-Diagnosed Multiple Myeloma (MM): Five (5) or More Focal Lesions and LDH Elevation Identify Inferior Survival in 402 Patients Receiving Total Therapy II (TT II)
Ronald Walker, Bart Barlogie, Rajesh Sethi, Edgardo Angtuaco, Elias Anaissie, Athanasios Fassas, Choo-Kee Lee, Raymond Thertulien, Frits van Rhee, Maurizio Zangari, Ernest Ferris, Guido Tricot

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MM frequently presents with plasmacytoma lesions superimposed on diffuse infiltration of the marrow which can be recognized on MRI (T1-weighted and STIR images). These MRI-focal lesions have previously been shown to contain malignant plasma cells morphologically, by flow cytometry, and by cytogenetics or FISH. These lesions are also underlying osteolytic lesions (OL), recognized on standard X-rays and also identify sites of future OL when treatment is ineffective. Toward achieving durable disease control with TT II (consisting of intensive remission induction, tandem autotransplants with melphalan 200 mg/m², consolidation chemotherapy for 1 year and interferon maintenance, up-front randomization to +/- thalidomide), MRI of the axial bone marrow was performed in 402 patients at baseline and at distinct phases of follow-up in order to determine, in this prospective study, whether previous pilot results can be confirmed, i.e. superior outcome with MRI-CT in addition to conventional diagnosis of CR (immunofixation negative and normal bone marrow aspirate and biopsy). This study reports on the first 402 of currently 470 patients enrolled with an accrual target of 660 patients. MRI data were categorized as to revealing hyper-, iso- or hypo-intense background; homogeneous versus heterogeneous; as well as the number of focal lesions present. The only statistically significant difference of pre-treatment MRI for predicting outcome was the number of focal lesions in the spine and pelvis, revealing significantly superior event-free survival (EFS) and overall survival (OS) with < 5 focal lesions, with 2 year estimates of EFS of 82% (75, 88) for < 5 focal lesions and 68% (59, 76) for 5 or more focal lesions (p = 0.004); similarly, 2 yr OS was 89% (84, 94) with < 5 focal lesions compared to 79% (72, 86) with 5 or more focal lesions (p = 0.007). Examination of potential associations with standard prognostic factors (SPF) such as β₂M, CRP, and the Durie-Salmon stage revealed significant associations of 5 or more focal lesions with Stage III (OR 3.1 [2.0, 5.0], p<0.001) and CRP 4 or more mg/L (OR 2.1 [1.1, 4.0], p = 0.02). Importantly, joint consideration of 12 SPF revealed that 5 or more focal lesions, present in 44% of patients, to retain independent significance for both EFS (HR 1.8 [1.2, 2.8], p = 0.008] and OS (HR 1.9 [1.1, 3.2], p = 0.02), together with LDH of 190 or more U/L (present in 27% of patients) (EFS, HR 1.9, p = 0.006; OS HR 2.9, p<0.001). We conclude that MRI defined focal lesions, present in approximately 50%, often without associated OL, identify a MM entity with distinct biological and clinical implications. Currently available gene expression profiling data are being examined to determine the genotypic equivalent of plasmacytoma-like growth patterns, as we had previously demonstrated unique genes that differentiated OL from non-OL using standard X-rays.
Keywords: Myeloma, MRI, Prognosis

• Introduction
• Aims of Study
• Methods
• Results
• Conclusions
• Future Directions

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