In general, progression to one of these malignant outcomes occurs at a rate of 2% to 3% per year. Individuals with higher serum IgM or lower serum albumin levels progress at faster rates than those with normal levels of these parameters. Light chain MGUS
Individuals diagnosed with light chain MGUS typically do not express detectable levels of an IgG, IgA, IgD, IgE, or IgM intact myeloma protein in their blood. Rather, they overexpress a monoclonal, aberrant free κ (i.e. kappa) or λ (i.e., lambda) immunoglobulin light chain. For diagnosis, the κ and λ free light chains are quantified by immunological methods and the ratio of κ to λ light chains is used to detect unbalanced light chain synthesis that is indicative of a monoclonal light chain plasma cell dyscrasia. Light chain MGUS is defined as a disorder in which a serum κ to λ free light chain ratio falls outside the normal range of 0.26–1.65 (mean =0.9) provided that it is not associated with: a) any of the CRAB criteria, b) a bone marrow plasma cell count of 10 or a higher percentage of nucleated cells, c) evidence of amyloid deposition (see Light chain deposition disease), and d) an accumulation of 0.5 or more grams of the monoclonal light chain in the urine over a 24-hour period.
However, more sensitive methods of detecting urinary and serum light chain myeloma proteins using enzyme-linked immunosorbent assays indicate that >60% of cases initially diagnosed as non-secretory multiple myeloma had abnormal levels of either a clonal κ or λ light chain in their urine or serum and therefore were better diagnosed as having light chain multiple myeloma. Based on the latter definition, non-secretory multiple myeloma represents ~1% of all multiple myeloma cases with formerly diagnosed non-secretory myelomas considered to be cases primarily of light chain multiple myeloma but on occasion "false non-secretors", i.e. cases in which there is evidence of myeloma protein secretion such as renal myeloma protein deposits.A Mayo Clinic study of 124 patients initially diagnosed as having non-secretory multiple myeloma were later found to be composed of 65% free light chain secretors and 35% true non-secretors. As a group, these patients response to therapy, time to disease recurrence, and overall survival were similar to typical myeloma patients. However, in a subset of patients diagnosed after 2001 and therefore treated with more effective therapy that included autologous stem-cell transplantation, prognosis was significantly better in non-secretory multiple myeloma patients (median survival 8.3 years) compared to typical myeloma patients (median survival 5.4 years). In addition, non-secretory patients exhibited a better prognosis than light chain-secretory patients.