Smoldering multiple myeloma 40 years later: a story of unintended disease

Introduction: Smoldering multiple myeloma (SMM) is a clonal plasma cell (PC) disorder considered a prelude to MM due to its greater malignant potential compared to monoclonal gammopathy of undetermined significance (MGUS). Despite tectonic changes in the SMM landscape that occurred since it was first distinguished four decades ago, SMM continues to represent a complex and controversial entity causing a great deal of diagnostic and management turmoil.Areas covered: Author addresses increasingly complicated, ambiguous, as well as some overlooked and misjudged aspects of SMM such as the disease identity, relationship to its counterparts, MGUS and overt MM, its niche in the modern classification of monoclonal gammopathies and management. The PubMed search (1980-2020) was conducted and the current NCCN guidelines reviewed in reference to the diagnosis and treatment of smoldering multiple myeloma.Expert opinion: A plethora of clinical and biological evidence points to SMM as a source of the ongoing and expanding uncertainty of this condition and calls into question its authenticity as a discrete entity. Until comprehensive testing can predict the progression of pre-myeloma conditions with the utmost precision, attempts at preemptive treatments will fail to answer the basic question of who will benefit from the early treatment and who will not.