Risk stratification and early intervention in smoldering multiple myeloma

Smoldering multiple myeloma (SMM) is a biologically diverse precursor to multiple myeloma (MM), characterized by varying risks of progression. Several validated risk stratification models help identify patients at the highest risk, who may benefit from early treatment at the precursor stage. Current guidelines recommend treatment with lenalidomide, with or without dexamethasone, or participation in clinical trials for patients with high-risk SMM. Recent data also support using daratumumab monotherapy, which has been shown to significantly delay progression to MM. However, uncertainties remain about the long-term benefits of early intervention, especially regarding its effects on overall survival, quality of life, and the risk-benefit ratio in this asymptomatic group. This review discusses current risk stratification models for SMM, summarizes evidence from key clinical trials on prevention strategies, and highlights the evolving landscape of ongoing research.