From the Guidelines
Evaluation of monoclonal gammopathy should begin with a complete blood count, comprehensive metabolic panel, serum protein electrophoresis (SPEP), serum immunofixation electrophoresis (SIFE), serum free light chain assay, and 24-hour urine protein electrophoresis with immunofixation, as recommended by the most recent guidelines 1. These tests help quantify the monoclonal protein and determine its type.
- Bone marrow aspiration and biopsy are essential to assess plasma cell percentage and clonality.
- Skeletal imaging should be performed using low-dose whole-body CT, PET/CT, or MRI to detect bone lesions. Additional testing includes beta-2 microglobulin, lactate dehydrogenase, and calcium levels to assess disease burden and prognosis.
- For suspected light chain amyloidosis, cardiac biomarkers (troponin, NT-proBNP) and tissue biopsy may be necessary. The evaluation aims to differentiate between monoclonal gammopathy of undetermined significance (MGUS), which requires monitoring every 6-12 months, and more serious conditions like multiple myeloma, Waldenström macroglobulinemia, or amyloidosis that require immediate treatment.
- Risk stratification is important as it guides the frequency of follow-up and helps predict the likelihood of progression to malignancy. The presence of specific immunoglobulin subtypes, the concentration of monoclonal protein, and abnormal free light chain ratios are key factors in determining risk, as supported by studies such as 1 and 1. However, the most recent and highest quality study 1 should be prioritized when making a definitive recommendation. It is also important to note that the evaluation of monoclonal gammopathy has evolved over time, with earlier studies such as 1, 1, and 1 providing a foundation for the current recommendations. But the latest study 1 provides the most up-to-date guidance on the evaluation and management of monoclonal gammopathy.
From the Research
Evaluation of Monoclonal Gammopathy
- The evaluation of monoclonal gammopathy involves several laboratory tests, including serum protein electrophoresis (SPEP), urine protein electrophoresis (UPEP), serum immunofixation (IFE), and serum-free light chain assays 2, 3, 4, 5, 6.
- Serum protein electrophoresis with high-resolution agarose gel is recommended as the first test for recognition of monoclonal gammopathies 2.
- Immunofixation is critical for the differentiation of a monoclonal from a polyclonal increase in immunoglobulins 2.
- Quantitation of immunoglobulins should be performed with a rate nephelometer, and the viscosity of serum should be measured if the patient has signs or symptoms of hyperviscosity syndrome 2.
- A 24-hour urine specimen should be obtained for determination of the total amount of protein excreted each day, and immunofixation of the urine should be performed on every patient who has an M-protein level greater than 1.5 g/dL (15 g/L) in the serum or in whom multiple myeloma, Waldenström's macroglobulinemia, primary amyloidosis, or a related disorder is suspected 2.
Laboratory Tests for Monoclonal Gammopathy
- High-resolution gel serum protein electrophoresis using a Sebia Hydragel 15 HR system was found to be more sensitive than a screening immunofixation method (CLIF) for the detection of paraproteins in patient serum 4.
- The sensitivity and specificity of HR SPEP were 95% and 85%, respectively, while CLIF had a sensitivity and specificity of 88% and 97%, respectively 4.
- Serum-free light chain assay is a useful test for the diagnosis and monitoring of monoclonal gammopathies, but its shortcomings and limitations should be considered 3.
- Urine testing is useful in the diagnosis and monitoring of light chain only lesions 3.
Clinical Practice and Guidelines
- Laboratory practice for monoclonal gammopathy testing varies widely across laboratories, and improving utilization management and report content, as well as recognition and development of laboratory-directed testing guidelines, may serve to enhance the clinical value of testing 5.
- Serum protein electrophoresis is an easy-to-perform laboratory test that can be used for detection and quantification of monoclonal gammopathy and should be recommended as a preliminary test for suspected cases of multiple myeloma 6.
- Monoclonal gammopathy of undetermined significance (MGUS) must be differentiated from multiple myeloma, as management and prognosis of these two conditions are totally different 6.