What are the causes of hyperproteinemia (elevated serum protein)?

From the Guidelines

High serum protein levels should be evaluated with serum protein electrophoresis (SPEP) and immunofixation to identify the specific proteins elevated, as recommended by the NCCN Guidelines for multiple myeloma 1. When considering the implications of high serum protein, it's crucial to understand that this condition can be a marker for various underlying health issues, including chronic inflammation, infections, dehydration, and certain blood disorders like multiple myeloma or monoclonal gammopathy of undetermined significance (MGUS). The initial diagnostic workup for such conditions, as outlined in the NCCN Guidelines, includes a comprehensive set of blood studies and biological assessments to differentiate between symptomatic and asymptomatic conditions 1.

Key points to consider in the evaluation of high serum protein include:

• The use of serum free light chain (FLC) assay, which has high sensitivity for screening multiple myeloma and related plasma cell disorders, and also provides prognostic value 1.
• The importance of assessing changes and proportions of various proteins, particularly the monoclonal protein (M-protein), to track disease progression and response to treatment 1.
• The need for bone marrow aspiration and biopsy to evaluate bone marrow plasma cell infiltration, and full skeleton radiographic survey or whole-body, low-dose CT to evaluate lytic bone lesions 1.
• The role of chromosome analysis by metaphase cytogenetics and fluorescence in situ hybridization (FISH) in identifying specific chromosomal abnormalities that can influence prognosis and treatment decisions 1.

Given the potential complexity and variability of conditions associated with high serum protein, a comprehensive diagnostic approach, as recommended by the most recent guidelines, is essential for accurate diagnosis and effective management. This approach should prioritize the identification of the underlying cause of the elevated protein levels, rather than solely focusing on the protein elevation itself, to ensure that treatment is appropriately targeted and effective in improving patient outcomes in terms of morbidity, mortality, and quality of life.

From the Research

High Serum Protein

• High serum protein is often associated with multiple myeloma, a type of blood cancer characterized by the proliferation of malignant plasma cells in the bone marrow 2.
• In multiple myeloma, high serum protein levels can lead to various complications, including hyperviscosity syndrome, renal failure, and increased risk of infections 3.
• Treatment of multiple myeloma often involves the use of novel agents, such as bortezomib, lenalidomide, and dexamethasone, which can help reduce serum protein levels and alleviate symptoms 4, 5, 3, 6.
• The combination of bortezomib, lenalidomide, and dexamethasone has been shown to be effective in treating relapsed and refractory multiple myeloma, with response rates ranging from 61% to 83% 5, 3.
• However, this combination can also lead to adverse effects, such as hyponatremia, thrombocytopenia, and anemia, which require careful monitoring and management 4, 5, 3, 6.

Treatment-Related Toxicities

• Hyponatremia is a common adverse effect of bortezomib-containing combination therapy, which can be caused by the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) 4.
• The development of SIADH can be triggered by the cessation of dexamethasone treatment, and hyponatremia can be successfully treated with prednisolone 4.
• Other treatment-related toxicities, such as grade 3 or 4 neutropenia, thrombocytopenia, and anemia, can also occur, highlighting the need for careful dose adjustment and monitoring 5, 3, 6.

Clinical Trials

• Several clinical trials have investigated the efficacy and safety of bortezomib, lenalidomide, and dexamethasone combination therapy in multiple myeloma, including the EVOLUTION study and the phase I/II study reported by 3 and 6.
• These studies have demonstrated the feasibility and efficacy of this combination, with high response rates and manageable toxicity profiles 5, 3, 6.