Smoldering multiple myeloma and monoclonal gammopathy of undetermined significance

Abstract

Smoldering multiple myeloma (SMM) consists of the presence of a serum M protein of 30 g/L or more and/or 10% or more bone marrow plasma cells (BMPCs), with no clinical manifestations or symptoms of myeloma. It accounts for approximately 10% of all myelomas, and the median time to progression to a symptomatic multiple myeloma ranges from 2 to 3 years. The main factors for progression are the plasma cell mass (M-protein size and percent of BMPCs), the spinal MRI pattern, the plasma cell proliferative index, and the variant of SMM ("evolving" vs "nonevolving"). Although treatment with thalidomide is promising (based on the results of two phase II trials), outside the context of a clinical trial, a watch-and-wait approach with clinical evaluation every 4 months is recommended until evident symptomatic disease progression occurs. Patients with monoclonal gammopathy of undetermined significance (MGUS) have a serum M protein lower than 30 g/L and a proportion of BMPCs of less than 10%, with no clinical findings or symptoms attributable to the monoclonal gammopathy. MGUS has a high prevalence, and its annual rate of malignant transformation is 1%, such that the actuarial probability of progression to a symptomatic monoclonal gammopathy at 25 years of follow-up is as high as 40%. The factors associated with a higher probability of malignant transformation are a relatively high plasma cell mass, immunoglobulin A M-protein type, and the "evolving" variant. It is recommended that patients with MGUS are monitored annually. Importantly, patients with asymptomatic monoclonal gammopathies must not be treated before the development of overt multiple myeloma.

Gene-expression signature of benign monoclonal gammopathy evident in multiple myeloma is linked to good prognosis

“…MM remains hypoproliferative, with a long lifespan of malignant B cells, that assumes high-grade proliferative features only in the terminal phase, from which all human MM cell lines have been derived. 8,9 Most genetic lesions typical of MM are already present at the MGUS stage. [10][11][12] Although these genetic abnormalities can be detected only in interphase cells in MGUS, their detection by metaphase karyotyping in one third of patients with MM reflects increased mitotic activity (possibly reflecting the ability of cells to proliferate outside the confines of the bone marrow milieu) and confers an adverse prognosis.…”

Molecular Imaging in Myeloma Precursor Disease

“…In patients with SMM, the pattern of spine involvement (focal, diffuse or variegated) on MR imaging is useful for predicting disease progression to MM (7, 8). The focal pattern is associated with the shortest progression, with an average of 6 months, compared with 16 months for diffuse and 22 months for the variegated pattern (8).…”

“…Based on current knowledge, the patterns of spine involvement (focal, diffuse or variegated) is one of the main factors in predicting progression of SMM to the symptomatic form of MM (7, 8). …”

Relevant prognostic features of multiple myeloma and the new International Staging System

“…Most patients with DurieSalmon Stage I multiple myeloma are not candidates for treatment and are omitted from many therapeutic studies; however, these patients regularly have smoldering or indolent multiple myeloma [4]. The Durie -Salmon system also requires determination of ''advanced bone lesions'' but does not define ''advanced.''…”