From the Guidelines
Smoldering multiple myeloma is a precancerous condition characterized by the presence of abnormal plasma cells in the bone marrow that produce an abnormal protein (M protein), but without causing symptoms or organ damage typically seen in active multiple myeloma. It represents an intermediate stage between monoclonal gammopathy of undetermined significance (MGUS) and active multiple myeloma. Patients with smoldering multiple myeloma have either 10-60% abnormal plasma cells in their bone marrow or an M protein level of 3 g/dL or higher in their blood, but they don't experience symptoms like bone pain, anemia, kidney problems, or high calcium levels.
Key Characteristics
- Presence of abnormal plasma cells in the bone marrow
- Production of abnormal protein (M protein)
- No symptoms or organ damage typically seen in active multiple myeloma
- Intermediate stage between MGUS and active multiple myeloma The standard approach for smoldering multiple myeloma is typically "watchful waiting" rather than immediate treatment, with regular monitoring every 3-6 months including blood tests, urine tests, and occasionally bone marrow examinations to check for progression to active myeloma, as recommended by the National Comprehensive Cancer Network guidelines 1.
Management Approach
- "Watchful waiting" rather than immediate treatment
- Regular monitoring every 3-6 months
- Blood tests, urine tests, and occasionally bone marrow examinations The risk of progression to active multiple myeloma is approximately 10% per year for the first five years, then decreases to about 3% per year for the next five years, and continues at a lower rate thereafter. Some high-risk patients may be candidates for clinical trials exploring early intervention strategies, but outside of clinical trials, treatment is generally not started until progression to symptomatic myeloma occurs, as supported by the study published in the Journal of the National Comprehensive Cancer Network 1.
Risk of Progression
- 10% per year for the first five years
- 3% per year for the next five years
- Continues at a lower rate thereafter The management of smoldering multiple myeloma should prioritize a "watchful waiting" approach, with regular monitoring and consideration of clinical trials for high-risk patients, to minimize the risk of progression to active multiple myeloma and optimize patient outcomes.
From the Research
Definition of Smoldering Multiple Myeloma (MM)
- Smoldering multiple myeloma (SMM) is an asymptomatic, intermediate stage between monoclonal gammopathy of undermined significance and overt multiple myeloma (MM) 2, 3, 4, 5, 6.
- SMM is characterized by the presence of serum M-protein ≥ 30 g/L and/or bone marrow plasma cell infiltration ≥ 10% without myeloma-related symptomatology 4, 5.
Risk of Progression
- Patients with SMM have a higher risk of progression to MM compared to those with monoclonal gammopathy of undermined significance 2, 3, 6.
- The risk of progression to MM varies based on clinical, laboratory, imaging, and molecular characteristics 5.
- Several markers are useful for identifying SMM patients at high risk of progression to active MM, including the size of the M-protein, bone marrow infiltration, serum-free light-chain ratio, and presence of immunoparesis 4.
Management and Treatment
- The standard of care for SMM is observation, with periodic monitoring, due to the lack of high-level evidence demonstrating survival or quality-of-life benefit with early intervention 2, 3, 4, 5, 6.
- However, recent studies have shown that early treatment with lenalidomide and dexamethasone may be beneficial for high-risk SMM patients 2, 4.
- A subset of patients with ultra-high-risk SMM, defined by biomarkers identifying patients with an ≥80% risk of progression within 2 years, is now reclassified as MM and may require optimal MM treatment 3, 6.