Prognostic implications of comprehensive imaging with PET-CT, MRI, and X-rays and their biological and molecular correlates in multiple myeloma (MM) treated with total therapy 3 (TT3)

Abstract

8532 Background: PET and MRI can reveal intramedullary focal lesions (FL) before osteolysis is detected on metastatic bone survey (MBS). Diagnostic merits, biological/molecular correlates, and outcome implications of the imaging techniques were prospectively and serially evaluated in 269 of 303 newly-diagnosed patients receiving TT3. Methods: Examined were FL number identified by PET (FDG-FL), CT portion of PET (CT-FL), MRI (MRI-FL), and MBS (MBS-FL); additionally, max-SUV of FL (SUV-FL), diffusely-involved bone marrow (SUV-DI), and extramedullary disease (EMD) on PET-CT. Results were compared, laboratory correlates examined (eg: gene expression profiling [GEP]-derived risk, molecular subgroups), and outcome implications determined. Results: Comparing anatomic sites, PET detected the highest mean FL followed by MRI and MBS (p<0.0001). Univariately significant implications on overall and event-free survival (OS, EFS) of FDG-FL, MBS-FL, and EMD may be explained by their link to other prognostic variables. Applying tertile frequency distributions of all imaging parameters, significant associations were seen for B2M with MBS-FL, FDG-FL, SUV-DI; CRP with MRI-FL, FDG-FL, CT-FL; GEP-defined high-risk with MRI-FL, FDG-FL, MBS-FL, SUV-FL; GEP low bone (LB) disease with MRI-FL, FDG-FL, SUV-FL; GEP Proliferation (PR) subgroup with MRI-FL, FDG-FL, MBS-FL, CT-FL. Yet on multivariate analysis, OS was independently adversely affected by both SUV-FL (>11) (p=0.001) and MRI >23 (p=0.043) in addition to cytogenetic abnormalities (CA) (p=0.005), B2M (>5.5mg/L) (p=0.005), and LDH ((ULN) (p=0.017). Even with GEP-defined high-risk (p=0.008), SUV-FL (>11) (p=0.009) retained independent significance in addition to CA (P<0.001) and CRP (>8mg/L) (p=0.020). Conclusions: This first prospective comprehensive imaging approach to MM showed that high SUV-FL had significant survival implications even after adjusting for powerful prognostic variables, especially GEP-defined risk. Multifaceted correlations of imaging variables also with molecular features of MM underscore the key role of bone (“soil”) for MM (“seed”) development and progression. [Table: see text]