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

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

doi:10.1038/s41408-020-00366-3

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 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.

Highlights

Smoldering multiple myeloma (SMM) represents a transitional stage between monoclonal gammopathy of undetermined significance (MGUS) and active multiple myeloma (MM)[1,2]
SMM was defined by the presence of either a serum monoclonal protein of ≥3 g/dL and/or ≥10% bone marrow plasma cells (BMPCs) without evidence of any CRAB symptoms
BMPCs infiltration (≥10%), and the ratio of serum free light chain (≥8 or

Summary

Introduction

Smoldering multiple myeloma (SMM) represents a transitional stage between monoclonal gammopathy of undetermined significance (MGUS) and active multiple myeloma (MM)[1,2]. Before International Myeloma Working Group (IMWG) revised the MM diagnostic criteria, SMM was defined by the presence of either a serum monoclonal protein of ≥3 g/dL (or ≥500 mg/24 h in urine or both) and/or ≥10% bone marrow plasma cells (BMPCs) without evidence of any CRAB symptoms (hypercalcemia, renal impairment, anemia, or lytic bone lesions). The Mayo Clinic and the Spanish Group had previously created different risk stratification models that can identify SMM patients with a 2-year risk of progression to MM of ≥50%. The Spanish model used the presence of ≥95% clonal plasma cells among all BMPCs by immunophenotyping and the presence of immune paresis and identifies a subgroup of patients having both features with a 50% risk of progression at 2 years[5]

Methods

Results

Conclusion