From the Guidelines
Hyperproteinemia is a significant indicator of malignancy, particularly in multiple myeloma, where elevated serum M-protein levels are a key diagnostic criterion, as outlined in the 2017 NCCN clinical practice guidelines in oncology 1. The relationship between hyperproteinemia and malignancy is well-established, with certain types of cancer, such as multiple myeloma, lymphomas, and leukemias, causing an increase in serum protein levels.
- Key points to consider:
- Multiple myeloma is characterized by the production of excessive amounts of monoclonal immunoglobulins (M proteins), leading to elevated total serum protein levels.
- The 2017 NCCN guidelines define progressive disease in multiple myeloma as an increase of 25% from the lowest confirmed response value in serum M-protein, among other criteria 1.
- Other cancers, such as solid tumors, can also trigger inflammatory responses, leading to high protein levels.
- Diagnostic tests, including serum protein electrophoresis, immunofixation, and free light chain assays, are essential for identifying specific protein abnormalities.
- Treatment for multiple myeloma typically involves combinations of proteasome inhibitors, immunomodulatory drugs, and corticosteroids.
- Important considerations:
- High protein levels can lead to complications like hyperviscosity syndrome, kidney damage, and increased infection risk.
- Monitoring and managing protein levels is crucial in cancer treatment, particularly in multiple myeloma, where serum M-protein levels are a key indicator of disease progression or response to treatment 1.
From the Research
Relationship between Hyperproteinemia and Malignancy
The relationship between hyperproteinemia and malignancy, specifically in the context of multiple myeloma, is complex and multifaceted. Hyperproteinemia refers to an excess of protein in the blood, which in the case of multiple myeloma, is often due to the overproduction of a specific type of protein called monoclonal immunoglobulins or M proteins by cancerous plasma cells.
Diagnostic Criteria and Risk Stratification
- Multiple myeloma accounts for approximately 10% of hematologic malignancies 2, 3, 4, 5.
- Diagnosis requires ≥10% clonal bone marrow plasma cells or a biopsy-proven plasmacytoma plus evidence of one or more multiple myeloma defining events (MDE) 2, 3, 4, 5.
- MDEs include CRAB features (hypercalcemia, renal failure, anemia, or lytic bone lesions), bone marrow clonal plasmacytosis ≥60%, serum involved/uninvolved free light chain (FLC) ratio ≥100, or >1 focal lesion on magnetic resonance imaging 2, 3, 4, 5.
- The presence of certain genetic abnormalities, such as del(17p), t(4;14), t(14;16), t(14;20), gain 1q, or p53 mutation, is considered high-risk multiple myeloma 3, 4, 5.
Treatment Approaches
- Induction therapy for patients eligible for autologous stem cell transplantation typically consists of bortezomib, lenalidomide, and dexamethasone (VRd) followed by transplantation 3, 4, 5.
- For high-risk patients, daratumumab, bortezomib, lenalidomide, and dexamethasone (Dara-VRd) is an alternative to VRd 3, 4.
- Maintenance therapy with lenalidomide is recommended for standard-risk patients, while bortezomib-based maintenance is needed for patients with high-risk disease 3, 4.
Hyperproteinemia as a Marker of Disease Activity
- Hyperproteinemia, in the form of elevated M protein levels, is a common feature of multiple myeloma and can serve as a marker of disease activity 2, 3, 4, 5.
- Reduction in M protein levels is often used as an indicator of response to treatment 6.
Ongoing Research and Emerging Therapies
- Studies continue to explore optimal treatment strategies for high-risk multiple myeloma, including the role of novel agents and combination regimens 6.
- Emerging therapies, such as chimeric antigen receptor T (CAR-T) cell therapy and bispecific antibodies, offer new options for patients with relapsed or refractory disease 5.