Multiple myeloma is the second most common blood cancer, with close to 160,000 new cases diagnosed globally per year.1,2 Despite increased availability of novel agents, the disease is characterized by a pattern of recurrent relapses and remains incurable for the majority of patients, leading to approximately 106,000 deaths per year, worldwide.2–4
In the United States, it is estimated that in 2018 there were 30,770 new cases of myeloma and an estimated 12,770 deaths from this disease.1,5
Multiple myeloma (MM) is a B-cell malignancy in which abnormal, clonal plasma cells proliferate and accumulate in the bone marrow. Myeloma cells disrupt normal bone marrow function and invade the surrounding bone causing bone destruction.6 The interactions between myeloma cells and stromal cells in a specialized niche in the bone marrow facilitate cell growth and disease progression, which can lead to anemia, thrombocytopenia, bone disease, hypercalcemia and renal impairment.6-8
Myeloma cells typically harbor one or more mutations in the genes responsible for immunoglobulin production. Additional mutations can develop in a clonal fashion, resulting in a heterogeneic population of myeloma cells in the bone marrow.9 Myeloma cells produce and secrete significant quantities of the immunoglobulin component, monoclonal protein (M-protein). Excess production of M-protein causes accumulation in the bone marrow and subsequently the bloodstream followed by the urine. In addition, abnormal monoclonal molecules can adhere to each other and/or other tissues such as blood cells, blood vessel walls, and other blood components, which can reduce blood flow and circulation.5
The stages of multiple myeloma are defined as asymptomatic or symptomatic/active disease according to the guidelines set by the International Myeloma Working Group (IMWG).10 Monoclonal Gammopathy of Undetermined Significance (MGUS) display M-protein less than 3.0 g/dL and bone marrow clonal plasma cells less than 10%. Smoldering multiple myeloma display M-protein greater than 3.0 g/dL and bone marrow clonal plasma cells between 10% and 60%. Symptomatic/active multiple myeloma is characterized by the presence of M-protein, greater than 60% bone marrow clonal plasma cells, and indicators of organ damage classified by the CRAB criteria. CRAB features include Calcium elevation, Renal dysfunction, Anemia, and Bone disease.6
CRAB criteria are used to help identify Multiple Myeloma. Myeloma is defined by the presence of monoclonal protein and one or more CRAB features and/ or indicators of organ damage:6
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