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

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

Journal: Blood cancer journal 2021;10(10):102

PMID: 33067414

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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.

Address: Servicio de Hematologia, Hospital Universitario de Salamanca, Centro de Investigación del Cáncer, Instituto de Biología Molecular y Cellular del Cáncer (Universitario de Salamanca-Consejo Superior de Investigaciones Científicas), Salamanca, Spain.; Division of Hematology, Mayo Clinic, Rochester, MN, USA. [email protected].; Hematology and Medical Oncology, Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece.; Department of HematoOncology, University Hospital Ostrava and Faculty of Medicine, Ostrava University, Ostrava, Czech Republic.; Department of Hematology, Amyloidosis and Myeloma Unit, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain.; Perlmutter Cancer Center, NY Langone Health, New York, NY, USA.; Department of Molecular Medicine, Amyloidosis Research and Treatment Center, Foundation 'Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo', University of Pavia, Pavia, Italy.; Department of Internal Medicine V, University Medical Hospital and National Center of Tumor Diseases, Heidelberg, Germany.; Department of Clinical Hematology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.; Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy.; Department of Haematology, London North West Healthcare, London, UK.; Service d'Hématologie, Hôpital Pitié Salpêtrière, Paris, France.; Department of Hematology, Sahlgrenska University Hospital, Goteborg and Skane University Hospital, Lund, Sweden.; Department of Experimental, Diagnostic and Specialty Medicine - DIMES, University of Bologna, Bologna, Italy.; Department of Hematology, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.; Department of Hematology, Hopital de La Milétrie, CHU, Poitiers, France.; Department of Hemato-Oncology, Hallym University Dongtan Sacred Heart Hospital, Hwasung, South Korea.; Department of Hematology, Hospital de Santa Maria, Lisboa, Portugal.; Department of Medicine, Center for Oncology, Hematology and Palliative Care, Wilhelminenspital, Vienna, Austria.; Department of Hematology and Medical Oncology, Atrium Health/Levine Cancer Institute, Charlotte, NC, USA.; Hematology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea.; Janssen Pharmaceuticals, Horsham, PA, USA.; Division of Hematology, Mayo Clinic, Rochester, MN, USA.; Cedars-Sinai Outpatient Cancer Center, Los Angeles, CA, USA.; Clinica Universidad de Navarra, CIMA, CIBERONC, IDISNA, Pamplona, Spain.

DOI: 10.1038/s41408-020-00366-3

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MeSH Terms: Aged, Biomarkers, Tumor, Disease Progression, Female, Follow-Up Studies, Humans, Immunoglobulin Light Chains, Male, Middle Aged, Models, Biological, Multiple Myeloma, Myeloma Proteins, Risk Factors