Toward a cure for multiple myeloma within a decade.

Multiple myeloma (MM), long viewed as incurable, is entering a transformative era marked by deeper remissions, prolonged survival, and the realistic prospect of cure. The greatest opportunity lies at diagnosis, before genomic heterogeneity and immune escape limit therapeutic impact. High-risk smoldering MM provides a preclinical window where early intervention with targeted antibodies or combinations can delay progression and, as in some trials, improve survival. Refining the threshold for treatment-entry requires integrated risk models that combine genomics, microenvironmental and immune profiling, and artificial intelligence. The therapeutic goal is sustained minimal residual disease (MRD) negativity at a sensitivity of 10⁻⁶, validated with functional imaging to exclude focal disease. Achieving two years of sustained MRD negativity in standard-risk and three years or longer in high-risk disease strongly predicts long-term progression-free survival; five years off therapy may approximate operational cure. Quadruplet induction, consolidation, and tailored maintenance regimens maximize depth and durability of response. To advance this vision, priorities include standardized MRD and imaging assays, MRD-adapted clinical trials, strategies balancing treatment toxicity with quality of life, and equitable global access. With decisive and risk-adapted strategies, achieving cure in MM within the next decade is no longer aspirational but increasingly within reach.