Multiple Myeloma: Clinical Aspects
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Multiple myeloma (MM) is a clonal B-cell malignancy with a terminally differentiated plasma cell (PC) phenotype characterized by the production of either intact immunoglobulins (Ig) or free light chains (FLC). The annual incidence is 5 cases per 100,000 persons. Median age at diagnosis is approximately 70 years. An evolutionary model in which MM is the result of the transformation of a previous condition of monoclonal gammopathy of undetermined significance (MGUS) is virtually the basis of almost all cases. In about 15% of cases diagnosis is suspected based on routine laboratory exams. In the remaining 85% most common clinical manifestations include hypercalcemia, renal failure, anemia, or bone lesions (defined as CRAB criteria). According to the revised International Myeloma Working Group (IMWG) diagnostic criteria, MM requiring the immediate start of therapy is defined by the presence of clonal bone marrow (BM) PCs ≥10%, or biopsy-proven bony or extramedullary plasmacytoma, along with at least one CRAB criteria or at least one of the new biomarkers of malignancy, including BM PCs ≥60% and/or involved/uninvolved serum FLC (sFLC) ratio ≥100 and/or >1 focal lesions on magnetic resonance (MRI) studies. Converserly, smoldering MM does not require therapy (with the exception of controlled clinical trials) and is defined by the presence of serum monoclonal protein (M-protein) ≥30 g/L or urinary M-protein ≥500 mg per 24 h and/or clonal BM PCs in the range between 10 and 60%, and absence of both CRAB criteria and biomarkers of malignancy or amyloidosis. Treatment paradigm includes different combinations of novel agents, including proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs) and monoclonal antibodies (mAb), combined or not with autologous stem cell transplantation (ASCT). The main treatment end point is to achieve the deepest response early in the course of the disease and maintain it as much long as possible.
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