From the Guidelines
Smoldering multiple myeloma (SMM) is typically asymptomatic, meaning patients do not exhibit the classic symptoms associated with active multiple myeloma, such as hypercalcemia, renal insufficiency, anemia, and bone lesions, as outlined in the NCCN guidelines 1.
Key Characteristics of Smoldering Myeloma
The defining characteristics of SMM include:
- Serum monoclonal protein IgG or IgA ≥3 g/dL
- Bence-Jones protein ≥500 mg/24 h
- Clonal bone marrow plasma cells 10%–60%
- Absence of myeloma-defining events or amyloidosis These criteria are crucial for differentiating SMM from active multiple myeloma, as noted in the study by Rajkumar et al. 1.
Detection and Monitoring
SMM is usually detected incidentally through blood tests showing elevated protein levels or an abnormal free light chain ratio, along with increased plasma cells in the bone marrow, as discussed in the guidelines 1. Regular monitoring is essential, with blood tests every 3-6 months and imaging studies annually, to watch for progression to active myeloma, which occurs at a rate of about 10% per year for the first five years, as mentioned in the NCCN guidelines 1.
Importance of Asymptomatic Nature
Understanding SMM's asymptomatic nature is important because treatment is typically withheld until progression to symptomatic disease occurs, though high-risk SMM patients may be considered for clinical trials of early intervention, as suggested by the study by Mateos et al. 1. The absence of symptoms is why SMM requires regular monitoring rather than immediate treatment, allowing for the detection of progression to active disease at an early stage, as outlined in the guidelines 1.
High-Risk Features
Some patients with certain characteristics, including IgG levels of >3 g/dL, IgA of >2 g/dL, or urinary Bence Jones protein of >1 g/24 h, have an increased risk of progression to active multiple myeloma, as noted in the study by Dispienzeri et al. 1. These high-risk features highlight the need for close monitoring and consideration of early intervention in selected cases, as discussed in the NCCN guidelines 1.
Clinical Trials
The NCCN believes that the best management of any cancer patient is in a clinical trial, and participation in clinical trials is especially encouraged for high-risk SMM patients, as stated in the guidelines 1. Clinical trials offer the opportunity for early intervention and potentially improved outcomes for patients with high-risk SMM, as suggested by the study by Rajkumar et al. 1.
From the Research
Symptoms of Smoldering Myeloma
The symptoms of smoldering myeloma are not always apparent, as it is an asymptomatic disorder. However, some common characteristics of smoldering myeloma include:
- At least 3 g/dL of serum M-protein and/or 10% to 60% bone marrow plasma cell infiltration with no myeloma-defining event 2
- No end-organ damage, such as anemia, bone lesions, renal failure, or hypercalcemia 3
- A median risk of progression to active disease of 50% in the first 5 years 3
Risk of Progression
The risk of progression to active multiple myeloma is not uniform and several markers are useful for identifying patients at high risk of progression 2. Some patients may be classified as having high-risk or ultrahigh-risk subgroups of smoldering myeloma, with a more likely evolution to multiple myeloma 3.
Monitoring and Treatment
Patients with smoldering myeloma are typically monitored closely to avoid complications of overt multiple myeloma, including anemia, bone lesions, renal failure, and hypercalcemia 4. Treatment may be considered for patients with high-risk smoldering myeloma, and may include lenalidomide plus dexamethasone 5, or other nonchemotherapeutic agents such as bisphosphonates, dexamethasone, and erythropoietin 4. The ideal timing and patient population for treatment are still being studied, as well as the identification of which agents would be of greatest benefit 3.