M-protein concentrations year-by-year over time prior to multiple myeloma. Two major patterns of MGUS prior to multiple myeloma: “evolving MGUS” and “non-evolving MGUS.” In about half the study population, the M-protein concentration and involved FLC-ratio levels showed a year-by-year increase prior to MM diagnosis, while the other half maintained largely stable abnormal serum protein levels up to the diagnosis of MM.⁴⁵  Currently, we do not know if this represents a genetic switch in the tumor cells, a change in the host, or a combination; neither do we know if these different M-protein concentration patterns represent different biology when MM arises. One might speculate that there could be differences in response to therapy and survival. Future studies need to address these and other related questions. On a clinical note, one has to keep in mind that stable M-protein or FLC levels do not exclude the development of MM development. Until better molecular markers for progression to MM are available, clinicians have to use clinical measures in combination with routine blood tests (including renal function, hemoglobin, and serum calcium) and serum and urine M-protein markers in their monitoring of MGUS patients. (Adapted from Landgren et al., 2009.⁴⁵ )