SMM is an asymptomatic precursor state of MM. Recently, MM was redefined to include biomarkers predicting a high risk of progression from SMM, thus necessitating a redefinition of SMM and its risk stratification. We assembled a large cohort of SMM patients meeting the revised IMWG criteria to develop a new risk stratification system.

We included 1996 patients, and using stepwise selection and multivariable analysis, we identified three independent factors predicting progression risk at 2 years: serum M-protein >2 g/dL, involved to uninvolved free light-chain ratio >20, and marrow plasma cell infiltration >20%. This translates into 3 categories with increasing 2-year progression risk: 6% for low risk; 18% for intermediate-risk, and 44% for high risk. The addition of cytogenetic abnormalities allowed separation into 4 groups (low risk with 0, the low intermediate risk with 1, the intermediate-risk with 2, and high risk with ≥3 risk factors) with 6, 23, 46, and 63% risk of progression in 2 years, respectively. The 2/20/20 risk stratification model can be easily implemented to identify high-risk SMM for clinical research and routine practice and will be widely applicable.