Glucose Metabolism in Brain and Liver as a Marker of Multiple Myeloma Progression

Overview

This study evaluated the brain-to-liver glucose uptake ratio (B2LR) using 18F-FDG PET/CT imaging in multiple myeloma patients. Findings suggest that B2LR varies with disease activity and may have prognostic implications, particularly in patients undergoing CAR-T therapy.

Background

18F-FDG PET/CT is a vital imaging modality for staging and monitoring multiple myeloma, assessing disease burden, extramedullary disease, and metabolic response to therapy. Tumors exhibit increased glucose uptake due to the Warburg effect, potentially competing with the brain for glucose. The brain normally shows high glucose metabolism, while the liver maintains relatively constant uptake, making the brain-to-liver ratio a useful comparative metric. This study hypothesized that B2LR differs between active disease and remission states in multiple myeloma.

Data Highlights

A total of 297 PET/CT image sets from 56 patients were analyzed for brain and liver glucose uptake. Subsequently, 134 patients undergoing CAR-T therapy had their B2LR assessed from PET/CT scans performed 7-10 days before lymphodepletion chemotherapy. Regions of interest (ROI) included five cerebral cortex areas and five liver areas per scan. Statistical analyses included Student’s t test, Mann-Whitney test, Pearson correlation, and Kaplan-Meier survival analysis.

Key Findings

• The brain-to-liver ratio (B2LR) was calculated from standardized uptake values (SUV) in cerebral cortex and liver ROIs.
• B2LR differed significantly between patients with active multiple myeloma and those in remission or partial response.
• Patients with extramedullary disease (EMD) showed distinct B2LR patterns correlating with poorer prognosis.
• In the CAR-T therapy cohort, pre-treatment B2LR was associated with progression-free survival (PFS) and overall survival (OS).
• Brain glucose uptake decreased relative to liver uptake in patients with high tumor metabolic activity, supporting the hypothesis of tumor-brain glucose competition.

Clinical Implications

B2LR derived from routine 18F-FDG PET/CT imaging may serve as a non-invasive biomarker to assess disease activity and prognosis in multiple myeloma. Monitoring B2LR could help identify patients at higher risk of relapse or progression, especially prior to CAR-T therapy. This metric may complement existing imaging assessments to guide therapeutic decision-making.

Conclusion

The brain-to-liver glucose uptake ratio on PET/CT imaging reflects metabolic competition between tumor and brain tissue in multiple myeloma and correlates with disease status and outcomes. B2LR holds promise as a prognostic imaging biomarker in this patient population.

References

1. International Myeloma Working Group (IMWG) -- Response Criteria and Risk Classification
2. Mayo Clinic IRB Approvals 2023-2025 -- Study Protocols