From the Guidelines
Monoclonal gammopathies should be managed based on the specific diagnosis, with regular monitoring for monoclonal gammopathy of undetermined significance (MGUS) and combination therapy for multiple myeloma, prioritizing early diagnosis to prevent end-organ damage. The spectrum of monoclonal gammopathies includes MGUS, smoldering multiple myeloma, multiple myeloma, Waldenström macroglobulinemia, and AL amyloidosis. For MGUS, which affects about 3% of people over 50, regular monitoring is recommended with serum protein electrophoresis every 6-12 months, as approximately 1% of cases progress to malignancy annually 1.
Key Considerations
- The risk of progression to malignancy is a critical factor in managing MGUS, with an average risk of 1% per year 1.
- Combination therapy with proteasome inhibitors, immunomodulatory drugs, and corticosteroids is typically used for multiple myeloma, often followed by autologous stem cell transplantation in eligible patients 1.
- Newer therapies, including monoclonal antibodies like daratumumab and isatuximab, offer additional treatment options for multiple myeloma.
- Early diagnosis is crucial to prevent end-organ damage, such as hypercalcemia, renal insufficiency, anemia, and bone lesions, which can occur in multiple myeloma 1.
Management Strategies
- Regular monitoring with serum protein electrophoresis every 6-12 months for MGUS 1.
- Combination therapy with proteasome inhibitors, immunomodulatory drugs, and corticosteroids for multiple myeloma, often followed by autologous stem cell transplantation in eligible patients 1.
- Consideration of newer therapies, including monoclonal antibodies, for multiple myeloma.
- Early diagnosis and treatment to prevent end-organ damage in multiple myeloma 1.
From the Research
Monoclonal Gammopathies
- Monoclonal gammopathy of undetermined significance (MGUS) is defined as the presence of a monoclonal protein (M-protein) produced by a small amount of plasma cells 2
- A fraction of MGUS patients develop clinical manifestations related to the monoclonal gammopathy despite not fulfilling criteria of multiple myeloma or other lymphoproliferative disorder, constituting an emerging clinical issue coined as monoclonal gammopathy of clinical significance (MGCS) 2
- The mechanisms involved in MGCS are poorly understood, and literature is scarce regarding management 2
Treatment of Monoclonal Gammopathies
- Treatment strategies for MGCS rely on the basis of symptomatic disease and the M-protein isotype 2
- A multidisciplinary approach is required to manage the clinical spectrum of MGCS, which involves symptoms related to renal, neurologic, skin, ocular, or bleeding manifestations 2
- The use of novel agents, including proteasome inhibitors and immunomodulatory drugs, has markedly improved outcomes in multiple myeloma (MM) patients, and may also be effective in treating MGCS 3, 4, 5
Novel Agents for Multiple Myeloma
- The combination of lenalidomide, bortezomib, and dexamethasone (RVD) is a standard of care for MM patients, and has shown efficacy in inducing responses and improving survival 3, 4
- The addition of a monoclonal antibody, such as daratumumab, to the RVD backbone has been shown to deepen responses and potentially provide longer disease control 4, 6
- Network meta-analyses have identified combinations of novel agents that may fare better than others in relapsed/refractory MM, including daratumumab and pegylated liposomal doxorubicin 5