Enhanced dynamic risk stratification of smoldering multiple myeloma.

Nature medicine
Authors
Abstract

Accurate prediction of risk of progression from smoldering multiple myeloma (SMM) to active multiple myeloma (MM) is paramount to individualized early therapeutic strategies with minimum risk of overtreatment. Current risk stratification models do not account for evolving biomarker trajectories. We assembled a cohort of 2,344 patients with SMM from seven international centers with longitudinal clinical and biological data to train and validate the Precursor Asymptomatic Neoplasms by Group Effort Analysis (PANGEA)-SMM risk models. Four evolving biomarkers were significantly associated with shorter time to progression: M-protein increase ≥0.2 g dl, involved/uninvolved serum free light chain ratio increase ≥20, creatinine increase >25% and hemoglobin decrease ≥1.5 g dl. PANGEA-SMM outperforms established models, including the 20/2/20 and IMWG models, by more accurately predicting progression (C-statistic = 0.79), even without biomarker history (C-statistic = 0.78) or recent bone marrow biopsy (C-statistic = 0.78). We present PANGEA-SMM to the community as an easy-to-use, open-access tool for risk stratification in SMM. Validation tools are available to compare PANGEA-SMM to established models.

Year of Publication
2026
Journal
Nature medicine
Date Published
03/2026
ISSN
1546-170X
DOI
10.1038/s41591-026-04304-x
PubMed ID
41876650
Links