Multiple myeloma is a disease characterized by the clonal expansion of malignant plasma cells.
While the cause of myeloma is unknown, it is presumed that multiple mutations induce the transformation of plasma cells. Such mutations may permit the cell to expand into a small clonal population, resulting in a condition called monoclonal gammopathy of undetermined significance (or MGUS).

If this clonal population becomes larger while retaining a low proliferative capacity, it results in smoldering multiple myeloma.

As both MGUS and smoldering myeloma feature an absence of symptoms and endorgan damage, the levels of Mprotein and bone marrow plasma cells are used to distinguish between the two.

If the Mprotein is lower than 3g/dL and the bone marrow contains fewer than 10% plasma cells, then a diagnosis of MGUS is conferred.

In contrast, if either the Mprotein is higher than 3g/dL or if more than 10% of the bone marrow population includes plasma cells, then smoldering myeloma is diagnosed.

Although patients with MGUS or smoldering myeloma are asymptomatic, it is thought that additional mutations drive the clonal plasma cell populations to evolve towards a more aggressive state that leads to endorgan damage and then becomes symptomatic, active multiple myeloma.

Active disease is diagnosed if endorgan damage is detected with the development of symptoms and high levels of both the Mprotein and plasma cells within the bone marrow.

Clinical diagnosis of active myeloma is based on at least three objective laboratory tests, as well as the presence of bone destruction, anemia, renal and nervous system dysfunction, and/or multiple severe infections. These symptoms vary and may exist in various combinations in newly diagnosed multiple myeloma patients.