5A recent randomized phase III clinical trial reported a prolongation in progressionfree survival (PFS) and overall survival (OS) with early treat ment of patients with high-risk smoldering multiple myeloma (SMM). 6 Typically, these patients are diagnosed incidentally on routine evaluations and have no end-organ damage. 7 Given that a key aspect of clinical medicine is “first, do no harm”, a dilemma exists regarding early intervention for SMM. Clinical trials in medicine are systematic investigations to develop generalizable knowledge. In the field of multiple myeloma, unanswered fundamental questions need to be addressed through clinical trials. Is earlier treatment in myelo ma adequate? When should treatment be initiated? What pop ulation is the most likely to benefit? What treatment strategy should we use? What type of disease monitoring after initial therapy should we employ?