[Significant changes in diagnostic and therapeutic procedures in smoldering multiple myeloma]

Smoldering multiple myeloma (SMM) is a precursor disease of multiple myeloma (MM) with an average annual risk of progression to MM of 10%. Several prognostic factors have been identified and combined in models to discriminate patient groups with different outcomes. These factors include size of the M-protein, plasma cell (PC) infiltration in the bone marrow (BM), serum free light-chain ratio, immunoparesis and percentage of aberrant BMPCs on flow cytometry or the presence of focal lesions on magnetic resonance imaging. The current standard of care has been to initiate treatment with progression to symptomatic MM. Current approaches aim at identifying patients with an ultra-high risk of progression (≥ 80% within the first 2 years) who are considered as 'early myeloma' patients requiring therapy. A recent trial on high-risk SMM patients, comparing early treatment with lenalidomide plus dexamethasone (Rd) versus observation, reported a benefit with respect to time to progression and survival for Rd-treated patients. Therefore, in 2014, the International Myeloma Working Group (IMWG) revised the diagnostic criteria and proposed to treat patients with ultra-high risk SMM as symptomatic MM. Promising markers for further studies may be high levels of circulating and high proliferative rate of PCs, abnormal PC phenotype with > 95% plus immunoparesis, evolving SMM, specific cytogenetic subtypes, genomic and additional biomarkers; all being acknowledged by the IMWG be added to the diagnostic criteria in the future, if any proves to be associated with a risk of progression of SMM to MM of at least 80% within 2 years.