International Myeloma Working Group risk stratification model for smoldering multiple myeloma (SMM)
María-Victoria Mateos, Shaji Kumar, Meletios A Dimopoulos, Verónica González-Calle, 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, Jesús San-Miguel
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.