[Toward a cure for multiple myeloma: multi-omics insights into disease pathogenesis and early therapeutic intervention]

Multiple myeloma (MM) invariably arises from precursor conditions, monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). Recent therapeutic advances have brought the prospect of cure closer than ever. In this review, we discuss how multi-omics analyses have advanced our understanding of MM pathogenesis, and provide a biological rationale for early therapeutic intervention at precursor stages. Risk stratification models have evolved from static to dynamic approaches; however, they remain largely dependent on tumor burden surrogates. Whole-genome sequencing has revealed the continuous genomic evolution from MGUS and SMM to active MM, while single-cell RNA sequencing and spatial analyses have demonstrated that immune microenvironmental dysregulation begins at precursor stages. These multi-omics findings support the clinical efficacy of early therapeutic intervention in high-risk SMM, providing a biological rationale for intervening during a window of opportunity before disease progression. Further integration of multi-omics data holds promise for ultimately achieving cure in multiple myeloma.