International Myeloma Working Group risk stratification model for smoldering multiple myeloma (SMM)

Smoldering multiple myeloma (SMM) is an asymptomatic precursor state of multiple myeloma (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 (HR: 2.1), involved to uninvolved free light-chain ratio >20 (HR: 2.7), and marrow plasma cell infiltration >20% (HR: 2.4). This translates into 3 categories with increasing 2-year progression risk: 6% for low risk (38%; no risk factors, HR: 1); 18% for intermediate risk (33%; 1 factor; HR: 3.0), and 44% for high risk (29%; 2–3 factors). Addition of cytogenetic abnormalities (t(4;14), t(14;16), +1q, and/or del13q) allowed separation into 4 groups (low risk with 0, low intermediate risk with 1, 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.


María-Victoria Mateos, Shaji Kumar, Meletios A. Dimopoulos, Verónica González-Calle1, Efstathios Kastritis, Roman Hajek, Carlos Fernández De Larrea, Gareth J. Morgan, Giampaolo Merlini, Hartmut Goldschmidt, Catarina Geraldes, Alessandro Gozzetti, Charalampia Kyriakou, Laurent Garderet, Markus Hansson, Elena Zamagni, Dorotea Fantl, Xavier Leleu, Byung-Su Kim, Graça Esteves, Heinz Ludwig, Saad Usmani, Chang-Ki Min, Ming Qi, Jon Ukropec, Brendan M. Weiss, S. Vincent Rajkumar, Brian G. M. Durie and Jesús San-Miguel


Mateos, MV., Kumar, S., Dimopoulos, M.A. et al. International Myeloma Working Group risk stratification model for smoldering multiple myeloma (SMM). Blood Cancer J. 10, 102 (2020).

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