What is the relationship between multiple myeloma and hyperproteinemia (elevated protein levels in the blood)?

From the Guidelines

Multiple myeloma is a primary cause of hyperproteinemia due to the excessive production of monoclonal immunoglobulins or fragments like light chains by cancerous plasma cells, and management focuses on treating the underlying disease with regimens that may include proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, and corticosteroids 1.

Key Points

• Multiple myeloma is characterized by the proliferation and accumulation of B-lymphocytes and plasma cells that synthesize monoclonal immunoglobulin (M-protein or paraprotein) in the bone marrow or extramedullary tissues 1.
• The overproduction of M-protein leads to elevated total protein levels in the blood, typically with an increased gamma globulin fraction on serum protein electrophoresis, and can cause hyperviscosity syndrome when severe 1.
• Management of multiple myeloma involves treating the underlying disease with regimens that may include:
  • Proteasome inhibitors (bortezomib, carfilzomib)
  • Immunomodulatory drugs (lenalidomide, pomalidomide)
  • Monoclonal antibodies (daratumumab)
  • Corticosteroids (dexamethasone)
• For severe hyperviscosity, plasmapheresis may be needed to rapidly reduce protein levels 1.
• Regular monitoring of serum protein levels, including serum protein electrophoresis and immunofixation, is essential to track disease activity and response to treatment 1.

Disease Monitoring and Treatment

The International Myeloma Working Group (IMWG) produced updated criteria in 2014 for the classification of plasma cell disorders, and BM aspiration and BM biopsy are performed at diagnosis to identify and quantify clonal PC percentage 1. Response and disease evolution are scored according to the international uniform response criteria for therapy in MM, and treatment outcomes have significantly improved over the last two decades, with multiple myeloma changing from an acute life-threatening cancer into a chronic, albeit mostly incurable, disease 1.

Prognostic Factors

The presence of most chromosomal aberrations in newly diagnosed patients has been proposed as an important prognostic factor, with several copy number abnormalities (CNAs) and translocations associated with poorer prognosis 1. High-throughput sequencing identifies a broader array of genomic alterations, such as point mutations, deregulation of gene expression, and copy number alterations (CNAs), which are expected to be recognized as genomic indicators of more aggressive disease in the future 1.

From the Research

Multiple Myeloma and Hyperproteinemia

• Multiple myeloma is a hematologic malignancy characterized by the presence of abnormal clonal plasma cells in the bone marrow, which can lead to hyperproteinemia due to the overproduction of monoclonal proteins 2.
• The diagnosis of multiple myeloma requires the presence of ≥10% clonal bone marrow plasma cells or a biopsy-proven plasmacytoma, along with evidence of one or more multiple myeloma defining events (MDE), such as CRAB (hypercalcemia, renal failure, anemia, or lytic bone lesions) attributable to the plasma cell disorder 3.
• Hyperproteinemia in multiple myeloma can lead to various complications, including renal impairment, anemia, and bone lesions, highlighting the need for effective treatment strategies 2.

Treatment of Multiple Myeloma

• The standard treatment for newly diagnosed multiple myeloma typically involves a combination of an injectable proteasome inhibitor (e.g., bortezomib), an oral immunomodulatory agent (e.g., lenalidomide), and dexamethasone, followed by autologous hematopoietic stem cell transplantation and maintenance therapy with lenalidomide 2.
• The addition of bortezomib to lenalidomide and dexamethasone has been shown to improve progression-free and overall survival in patients with newly diagnosed multiple myeloma 4.
• The use of lenalidomide, bortezomib, and dexamethasone as induction therapy has been associated with deepening responses and improved outcomes in patients with multiple myeloma 5, 6.

Management of Hyperproteinemia

• The management of hyperproteinemia in multiple myeloma typically involves reducing the production of monoclonal proteins through effective treatment of the underlying disease 2.
• Plasma exchange may be considered in patients with severe hyperproteinemia and associated complications, such as renal impairment or hyperviscosity syndrome 2.
• The use of novel agents, such as monoclonal antibodies, may also be effective in reducing monoclonal protein production and improving outcomes in patients with multiple myeloma 3, 5.