From the Guidelines
Elevated IgG monoclonal protein necessitates a comprehensive diagnostic workup to differentiate between benign monoclonal gammopathy of undetermined significance (MGUS) and more severe conditions like multiple myeloma, lymphoma, or amyloidosis, as outlined in the 2017 NCCN Clinical Practice Guidelines in Oncology 1. The initial evaluation should include a complete blood count, comprehensive metabolic panel, serum protein electrophoresis with immunofixation, serum free light chain assay, and 24-hour urine protein electrophoresis.
- Key components of the diagnostic workup include:
- Serum analysis for quantitative immunoglobulin levels (IgG, IgA, and IgM) and serum protein electrophoresis to identify the type of M-protein present
- Urine analysis for total protein, urine protein electrophoresis, and urine immunofixation electrophoresis to detect urinary M-protein
- Serum free light chain assay to assess for plasma cell disorders, including MGUS, smoldering myeloma, and active myeloma
- Bone marrow biopsy and skeletal survey or low-dose whole-body CT scan to evaluate bone marrow plasma cell infiltration and lytic bone lesions
- The distinction between MGUS and multiple myeloma is crucial, as MGUS has a 1% annual risk of progression to multiple myeloma, while active multiple myeloma requires immediate treatment to prevent complications like bone fractures, renal failure, anemia, and hypercalcemia, as noted in the guidelines 1. A comprehensive diagnostic workup, as recommended by the NCCN guidelines, is essential for accurate diagnosis and treatment planning, and should be guided by the most recent and highest quality evidence, such as the 2017 NCCN Clinical Practice Guidelines in Oncology 1.
From the Research
Elevated IgG Monoclonal Protein
- Elevated IgG monoclonal protein is associated with monoclonal gammopathy of undetermined significance (MGUS) 2
- The risk of finding bone marrow plasma cell (BMPC) infiltration ≥10% in patients with an M-spike ≤ 1.5 g/dL is very low (7.3%), although significantly different according to IgH isotype (4.7% for IgG vs. 20.5% for IgA) 2
- The risk of finding bone lesions with M-spike ≤ 1.5 g/dL is negligible (2.5%), regardless of IgH isotype 2
- In asymptomatic patients with M-spike of small amount (≤1.5 g/dL), BMPC evaluation may be reasonably avoided in patients with IgG M-spike, while should always be part of diagnostic workup in the presence of IgA M-spike 2
- Serum tests used for the screening and diagnosis of monoclonal gammopathies include serum protein electrophoresis (SPE), immunofixation (IFE) and immunosubtraction capillary electrophoresis, serum free light chains, quantitative immunoglobulins, and heavy/light-chain combinations 3
- Guideline-concordant management of MGUS is determined by predicted risk of progression to malignant disease, which depends on subtype of immunoglobulin, M protein concentration, and free light chain ratio 4
- Patients with low-risk MGUS can safely defer bone marrow biopsy and advanced imaging, and should undergo periodic laboratory monitoring 4
- Intermediate- and high-risk MGUS should trigger bone marrow biopsy and bone imaging to detect overt MM and shorter monitoring intervals 4
- Monoclonal gammopathy of renal significance (MGRS) includes all kidney disorders caused by a monoclonal protein (M-protein) secreted by a small plasma cell clone or other B-cell clones in patients who do not meet the diagnostic criteria for multiple myeloma or other B-cell malignancies 5
- A combined haematologic and nephrologic approach is crucial to establish the causative role of the M-protein in the pathogenesis of kidney disease 5
- Clone-directed therapy, which may include autologous stem cell transplantation in eligible patients, often results in improved outcomes 5
- Routine clinical laboratory techniques that currently are recommended for use in identifying monoclonal gammopathies from serum and urine include high-resolution electrophoresis, methods for quantifying immunoglobulins, immunofixation electrophoresis, and identification of cryoglobulins and immune complexes 6