What are the implications of hyperproteinemia in multiple myeloma (Plasma Cell Myeloma)?

From the Guidelines

Hyperproteinemia in multiple myeloma is a condition that requires prompt treatment with combination therapy, including proteasome inhibitors, immunomodulatory drugs, and corticosteroids, to reduce the production of abnormal proteins and prevent serious complications. According to the European Journal of Nuclear Medicine and Molecular Imaging 1, multiple myeloma (MM) is a heterogeneous and complex disease characterized by the production and secretion of an M-protein, which can cause organ damage and serve as a marker for disease activity. The treatment of MM has dramatically changed over the last two decades, with the introduction of new drug classes such as proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies.

Key Considerations

• The International Myeloma Working Group (IMWG) produced updated criteria in 2014 for the classification of plasma cell disorders, which includes the measurement of serum free light chain (SFLC) production and the identification of specific genetic abnormalities 1.
• The treatment of MM should take into account specific factors including age, frailty, comorbidities, previous treatments, drug availability, and patient preference, as recommended by the European Hematology Association (EHA) and European Society for Medical Oncology (ESMO) 1.
• Regular MM disease monitoring is primarily performed by sequential measurements of the M-protein, and if indicated, BM aspiration, e.g. measurement of minimal residual disease (MRD) and/or imaging investigations 1.

Treatment Approach

• For newly diagnosed patients, a common regimen is RVd (lenalidomide 25mg daily on days 1-14, bortezomib 1.3mg/m² on days 1,4,8, and 11, and dexamethasone 40mg weekly) for 3-4 cycles, followed by autologous stem cell transplantation if eligible.
• Supportive care includes hydration to prevent renal damage from protein casts, bisphosphonates for bone protection, and monitoring for hyperviscosity syndrome.
• Regular assessment of serum protein levels, complete blood counts, and renal function is essential to monitor the response to treatment and prevent complications.

Outcome

• The hyperproteinemia resolves as treatment reduces the tumor burden and decreases the production of abnormal proteins.
• Prompt treatment is crucial as untreated hyperproteinemia can lead to serious complications including renal failure, hyperviscosity syndrome, and increased infection risk.

From the Research

Hyperproteinemia in Multiple Myeloma

• Hyperproteinemia is a condition characterized by an excess of protein in the blood, which can be a symptom of multiple myeloma 2.
• Multiple myeloma is a hematologic malignancy that accounts for approximately 10% of hematologic malignancies, and it is diagnosed in an estimated 34,920 people in the US and approximately 588,161 people worldwide each year 3.
• The diagnosis of multiple myeloma requires ≥10% clonal bone marrow plasma cells or a biopsy-proven plasmacytoma plus evidence of one or more multiple myeloma defining events (MDE), including CRAB (hypercalcemia, renal failure, anemia, or lytic bone lesions) attributable to the plasma cell disorder 2.

Treatment Options for Multiple Myeloma

• The standard first-line (induction) therapy for multiple myeloma consists of a combination of an injectable proteasome inhibitor (e.g., bortezomib), an oral immunomodulatory agent (e.g., lenalidomide), and dexamethasone, which is associated with a median progression-free survival of 41 months 3.
• For patients who are candidates for autologous stem cell transplantation, induction therapy with bortezomib, lenalidomide, and dexamethasone (VRd) is given for approximately 3-4 cycles, followed by autologous stem cell transplantation (ASCT) 2.
• In high-risk patients, daratumumab, bortezomib, lenalidomide, and dexamethasone (Dara-VRd) is an alternative to VRd 2.

Management of Relapsed or Refractory Multiple Myeloma

• For patients with relapsed or refractory multiple myeloma, a triplet regimen is usually needed, with the choice of regimen varying with each successive relapse 2.
• The combination of pomalidomide, bortezomib, and dexamethasone has shown promising results in phase 1/2 trials of patients with relapsed or refractory multiple myeloma 4.
• 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 5.