MGUS and Smoldering Multiple Myeloma: Diagnosis and Epidemiology
Monoclonal gammopathy of undetermined significance (MHUS) is characterized by the presence of a serum M-protein less than 3 g/dL, less than 10 % clonal plasma cells in the bone marrow, and the absence of myeloma-defining event. Smoldering multiple myeloma
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Abstract
Monoclonal gammopathy of undetermined significance (MHUS) is characterized by the presence of a serum M-protein less than 3 g/dL, less than 10 % clonal plasma cells in the bone marrow, and the absence of myeloma-defining event. Smoldering multiple myeloma (SMM) is an asymptomatic disorder characterized by the presence of ≥3 g/dL serum M-protein and/or 10–60 % bone marrow plasma cell infiltration with no myeloma-defining event. The risk of progression to multiple myeloma (MM) requiring therapy varies greatly for individual patients, but it is uniform and 1 % per year for MGUS, while higher (10 % per year) and not uniform for SMM patients. The definition of MM was recently revisited patients previously labeled as SMM with a very high risk of progression (80–90 % at 2 years) were included in the updated definition of MM requiring therapy. The standard of care is observation for MGUS patients and although this also applies for SMM, a recent randomized trial targeting high-risk SMM showed that early intervention was associated with better progression-free and overall survival. Biomarkers have become an integrated part of diagnostic criteria for MM requiring therapy, as well as clinical risk stratification of patients with SMM. This paper reviews and discusses clinical implications for MGUS and SMM patients. Keywords
Multiple myeloma requiring therapy Monoclonal gammopathy of undetermined significance Smoldering myeloma
M.-V. Mateos (&) University Hospital of Salamanca/IBSAL, Paseo San Vicente, 58-182, 37007 Salamanca, Spain e-mail: [email protected] O. Landgren Myeloma Service, Memorial Sloan-Kettering Cancer Center, New York, USA © Springer International Publishing Switzerland 2016 A.M. Roccaro and I.M. Ghobrial (eds.), Plasma Cell Dyscrasias, Cancer Treatment and Research 169, DOI 10.1007/978-3-319-40320-5_1
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M.-V. Mateos and O. Landgren
Introduction
In 1978, Monoclonal gammopathy of undetermined significance (MGUS) was described by Kyle and Greipp and 2 years later, based on a series of six patients who met the criteria for multiple myeloma (MM) but whose disease did not have an aggressive course, the same authors coined the term smoldering multiple myeloma (SMM) [1]. In 2014, the International Myeloma Working Group (IMWG) updated the definition of multiple myeloma (MM) which in turn impacted the definition of both MGUS and SMM [2]. MGUS diagnosis requires the presence of 11 mg/dL); (2) renal insufficiency: serum creatinine >177 μmol/L (2 mg/dL) or creatinine clearance 2 g/dL below the lower normal limit, or a hemoglobin value 1 focal lesions revealed by MRI studies
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Diagnostic Work-up
Initial investigation of a patient with suspected MGUS or SMM should include the tests shown in Table 2, which are coincidental with those used for a correct diagnosis of MM requiring therapy [6]. As far as SMM is concerned, due to the
Table 2 Work-up for newly diagnosed MGUS and SMM patients
• Medical history and physical examination • Hemogram • Biochemical studies, including of creatinine and calcium levels; Be
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