From the Guidelines
Smoldering myeloma is a precancerous condition characterized by the presence of abnormal plasma cells in the bone marrow (10-60%) and elevated M-protein in the blood (≥3 g/dL) or urine, but without any myeloma-defining events or symptoms like bone lesions, anemia, kidney problems, or hypercalcemia. This condition falls between monoclonal gammopathy of undetermined significance (MGUS) and active multiple myeloma, and patients with smoldering myeloma don't typically require immediate treatment, but instead undergo regular monitoring every 3-6 months with blood tests, urine tests, and occasional bone marrow examinations to watch for progression to active myeloma 1. The risk of progression is approximately 10% per year for the first 5 years, then decreases to about 3% annually for the next 5 years, and becomes even lower thereafter 1. High-risk smoldering myeloma patients (identified through specific biomarkers) may be candidates for clinical trials or early intervention strategies.
Some key characteristics of smoldering myeloma include:
- Elevated M-protein in the blood (≥3 g/dL) or urine
- Presence of abnormal plasma cells in the bone marrow (10-60%)
- Absence of myeloma-defining events or symptoms like bone lesions, anemia, kidney problems, or hypercalcemia
- Increased risk of progression to active myeloma, particularly in the first 5 years after diagnosis
The management of smoldering myeloma typically involves regular monitoring and observation, rather than immediate treatment, as outlined in the NCCN clinical practice guidelines in oncology 1. However, high-risk patients may benefit from early intervention strategies or participation in clinical trials 1.
It's worth noting that the understanding of smoldering myeloma is evolving rapidly, and some studies have identified specific biomarkers and risk factors that can help predict the risk of progression to active myeloma 1. These factors include elevated levels of IgG or IgA, abnormal free light chain ratios, and the presence of certain genetic mutations.
Overall, smoldering myeloma is an important condition to recognize and monitor, as it can progress to active myeloma if left untreated. Regular monitoring and observation are essential for patients with smoldering myeloma, and high-risk patients may benefit from early intervention strategies or participation in clinical trials.
From the Research
Definition of Smoldering Myeloma
- Smoldering multiple myeloma (SMM) is an asymptomatic clonal plasma cell disorder that is distinguished from monoclonal gammopathy of undetermined significance by a much higher risk of progression to multiple myeloma (MM) 2.
- SMM is characterized by clonal bone marrow plasma cells (BMPC) ≥ 10% and/or M protein level ≥ 30 g/L in the absence of end organ damage 3.
- It represents an intermediate stage between monoclonal gammopathy of undetermined significance (MGUS) and symptomatic MM 3.
Risk of Progression
- The risk of progression to symptomatic MM is not uniform, and several parameters have been reported to predict the risk of progression, including the level of M protein and the percentage of BMPC, the proportion of immunophenotypically aberrant plasma cells, and the presence of immunoparesis, free light-chain (FLC) ratio, peripheral blood plasma cells (PBPC), pattern of serum M protein evolution, abnormal magnetic resonance imaging (MRI), cytogenetic abnormalities, IgA isotype, and Bence Jones proteinuria 3.
- High-risk SMM patients have a higher risk of progression to MM, and early treatment may be beneficial in this subgroup 4, 5.
Treatment Strategies
- Treatment for SMM is still a matter of debate, but recent trials have shown that early treatment can delay the onset of MM and improve overall survival in high-risk patients 4, 5.
- Patients with newly diagnosed high-risk SMM should be offered therapy with lenalidomide or lenalidomide plus dexamethasone (Rd) for 2 years, or enrollment in clinical trials 5.
- Patients with low-risk SMM should be observed without therapy every 3-4 months 5.