MRI lesion burden as a predictor of progression and survival in smoldering multiple myeloma.

e19578 Background: The presence of multiple MRI focal lesions is a key diagnostic criterion for multiple myeloma (MM). Some patients with smoldering multiple myeloma (SMM) may progress to MM. This study aims to evaluate the role of MRI lesions in predicting progression from SMM to MM and to characterize their clinical significance in both the overall SMM cohort and in the subset of patients who progressed to MM. Methods: We conducted a large retrospective study of patients diagnosed with SMM up to 2024 at the University of Arkansas for Medical Sciences (UAMS) Myeloma Center. SMM patients were followed regularly with repeat myeloma marker assessments and advanced imaging, including MRI, MRI diffusion-weighted imaging with background suppression (MRI DWIBS), and positron emission tomography (PET) scans. A total of 746 SMM patients with MRI data were analyzed, stratified by the number of MRI focal lesions (0, 1, 2, and >2). A subset of 315 patients (42%) who progressed to MM was further evaluated. Demographics, genetic risk factors, lesion location, disease progression rates, and survival outcomes were assessed. Results: With a median follow-up of 9.8 years (95% confidence interval [CI]: 9.2–10.6 years), no significant differences were found in age, sex, or race across the different MRI lesion cohorts (p>0.05). The median number of MRI studies per patient before MM diagnosis was 5, with a range of 1–49, and PET scans were performed a median of 4 times, with a range of 1–44. Patients with >2 MRI focal lesions had a significantly higher likelihood of progression to MM (80.4%) compared to those with no lesions (28.7%), one lesion (47.7%), or two lesions (67%) (p<0.001). In patients who developed MM, a higher UAMS gene expression profile score was associated with a greater number of MRI lesions. MRI lesions were most commonly observed in the vertebrae (22.7%), pelvis (12.2%), humerus (6%), femur (5.6%), and ribs (3.4%). Among those with a single MRI lesion, the most frequent locations were the pelvis (78.5%), vertebrae (52.3%), femur (6.8%), and humerus (4.5%). Additionally, having at least two lesions was associated with a shorter time to progression to MM (p=0.032). Notably, some patients with no MRI lesions showed focal lesion avidity on PET scans, while others with MRI lesions did not show corresponding focal lesions on PET scans (20.6%). No difference in overall survival was observed based on the presence of MRI focal lesions (p>0.05). Conclusions: The number of MRI focal lesions is a strong predictor of progression to MM. Advanced imaging techniques, such as MRI and PET, are essential for comprehensive evaluation of smoldering myeloma, as some lesions may be missed by a single imaging modality. Specifically, some patients without MRI-detected lesions showed focal lesion avidity on PET scans, while others with MRI lesions had no corresponding findings on PET, highlighting the importance of multimodal imaging for accurate disease monitoring and prognostication.