Interpretation

Monoclonal Gammopathies:

-A monoclonal IgG or IgA of greater than 3 g/dL is consistent with multiple myeloma (MM).

-A monoclonal IgM of greater than 3 g/dL is consistent with macroglobulinemia.

-A monoclonal IgG, IgM, or IgA of less than 3 g/dL may be consistent with monoclonal gammopathy of undetermined significance (MGUS), light chain (AL) amyloidosis, well as other monoclonal gammopathies of clinical significance.

-If the initial identification of a serum M-spike is greater than 1.5 g/dL, then order a follow-up MPU / Monoclonal Protein Studies, 24 Hour, Urine to evaluate renal impairment due to the M-protein

-If the initial identification of an IgM, IgA, or IgG M-spike greater than 4 g/dL, greater than 5 g/dL, and greater than 6 g/dL, respectively, then SVISC / Viscosity, Serum should be ordered to rule out hyperviscosity syndrome.

-Patients with monoclonal light chain diseases who have no serum or urine M-spike may be monitored with the quantitative serum free light chain (FLC) assay.

-Patients with IgD or IgE can be followed using quantitative IgD or IgE measurements.

-Patients with monoclonal Ig heavy chains (gamma, alpha and mu) can be detected by the Mass-Fix assay.

-A small subset of MM patients (<1%) have malignant plasma cells that do not secrete an M-protein. Thus, these non-secretory MM patients need additional clinical testing to establish the diagnosis.

-Patients with normal serum protein electrophoresis and IFE can have positive results on Mass-Fix testing due to the increased sensitivity of the assay.

Detection of Therapeutic Monoclonal Antibodies:)

-Patients who are receiving therapeutic monoclonal antibodies (t-mAb) therapies can have a "pseudo" monoclonal protein (M-protein) depending on the level of the t-mAb in the blood. These t-mAb have predictable light chain mass to charge values. The lab has a limited (but expanding) number of t-mAb for which a comment is provided. If an M-protein is detected with a mass, isotype, and concentration similar to a t-mAb in the database, a comment is added to the report : "A monoclonal [isotype] is present with a light chain mass suggestive of [t-mAb name]. If the patient is not on [t-mAb name] the monoclonal [isotype] is indicative of a monoclonal gammopathy. Given that some M-proteins mass, isotype, and concentration will match a t-mAb, it is possible that the named t-mAb is not present and is in fact a low-level M-protein associated with a monoclonal gammopathy. If the patient has no history of taking the named t-mAb, then the reported M-protein is likely associated with a monoclonal gammopathy."

-In studies performed at Mayo Clinic, it is possible to see daratumumab for 9 months after the cessation of treatment.

-Mass-fix testing will not quantitate albumin, alpha-1-trypisin, alpha-2-macroglobulins or the beta fractions.

MGUS Prognosis:

-Low-risk MGUS patients are defined as having an M-spike of less than 1.5 g/dL, IgG monoclonal protein, and a normal FLC K/L (kappa/lambda) ratio (0.25-1.65), and these patients have a lifetime risk of progression to MM of less than 5%.

-High-risk MGUS patients (M-spike >1.5, IgA or IgM, abnormal FLC ratio) have a lifetime risk of progression to MM of 60%.

Other Abnormal Findings:

-IgG, IgA, and free light chain M-proteins with reported light chain glycosylation have demonstrated to be a risk factor for AL amyloidosis.

-IgM M-proteins with light chain glycosylation have been demonstrated to be associated with cold agglutinin disease.

-Persistent elevated immunoglobulin levels are consistent with autoimmune disease, IgG4 related disease and liver failure.