Smoldering multiple myeloma in transition: redefining early myeloma in the modern era

Smoldering multiple myeloma (SMM) has long been viewed as an intermediate precursor state, monitored until symptoms or organ dysfunction signaled the transition to active multiple myeloma (MM). Over the past decade, however, major advances in molecular biology, modern imaging, and immunotherapy have reshaped our understanding of early plasma cell disorders. The recent FDA approval of daratumumab for high-risk SMM marks a historic turning point. For the first time, early intervention is not only feasible but clinically validated. This evolving framework challenges long-standing assumptions regarding diagnostic boundaries, risk stratification, and the traditional "watch-and-wait" paradigm. It is logical to conjecture that emerging and future technologies will redefine portions of today's SMM population as early myeloma, while others may ultimately be reclassified as benign monoclonal gammopathies. An interesting question is whether there will be any SMM patients left? This article reviews how the field has arrived at this new therapeutic era, outlines its limitations, and highlights key scientific and clinical questions that will shape the next generation of SMM research and care.