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

Mateos, María Victoria ; Kumar, Shaji ; Dimopoulos, Meletios A. ; González-Calle, Verónica ; Kastritis, Efstathios ; Hajek, Roman ; De Larrea, Carlos Fernández ; Morgan, Gareth J. ; Merlini, Giampaolo and Goldschmidt, Hartmut , et al. (2020) In Blood Cancer Journal 10(10).
Abstract

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... (More)

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.

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@article{bc0b906f-394b-43da-aa07-66639751a2a3,
  abstract     = {{<p>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 &gt;2 g/dL (HR: 2.1), involved to uninvolved free light-chain ratio &gt;20 (HR: 2.7), and marrow plasma cell infiltration &gt;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.</p>}},
  author       = {{Mateos, María Victoria and Kumar, Shaji and Dimopoulos, Meletios A. and González-Calle, Verónica and Kastritis, Efstathios and Hajek, Roman and De Larrea, Carlos Fernández and Morgan, Gareth J. and Merlini, Giampaolo and Goldschmidt, Hartmut and Geraldes, Catarina and Gozzetti, Alessandro and Kyriakou, Charalampia and Garderet, Laurent and Hansson, Markus and Zamagni, Elena and Fantl, Dorotea and Leleu, Xavier and Kim, Byung Su and Esteves, Graça and Ludwig, Heinz and Usmani, Saad and Min, Chang Ki and Qi, Ming and Ukropec, Jon and Weiss, Brendan M. and Rajkumar, S. Vincent and Durie, Brian G.M. and San-Miguel, Jesús}},
  issn         = {{2044-5385}},
  language     = {{eng}},
  number       = {{10}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Blood Cancer Journal}},
  title        = {{International Myeloma Working Group risk stratification model for smoldering multiple myeloma (SMM)}},
  url          = {{http://dx.doi.org/10.1038/s41408-020-00366-3}},
  doi          = {{10.1038/s41408-020-00366-3}},
  volume       = {{10}},
  year         = {{2020}},
}