Smoldering myeloma is a condition characterized by an increase in abnormal plasma cells within the bone marrow or specific proteins in the blood or urine. This condition often presents without overt symptoms. This article aims to explain what smoldering myeloma is and how it differs from active cancer.
Understanding Smoldering Myeloma
Smoldering multiple myeloma (SMM), sometimes referred to as asymptomatic myeloma, is a precursor condition to active multiple myeloma. It involves the presence of abnormal plasma cells in the bone marrow, typically ranging from 10% to 60%, and/or the detection of an abnormal protein, called M-protein, in the blood or urine. Individuals with smoldering myeloma generally do not experience any symptoms or signs of organ damage that are characteristic of active multiple myeloma. The condition is frequently discovered incidentally during routine blood tests or health checks.
Is It Cancer? The Distinction Explained
Smoldering myeloma is classified as a pre-malignant or pre-cancerous condition, meaning it is not active cancer itself but carries a risk of progression to active multiple myeloma. The key difference between smoldering myeloma and active multiple myeloma lies in the absence of organ damage in the former. Active multiple myeloma is diagnosed when the abnormal plasma cell proliferation leads to specific signs of organ damage, often summarized by the “CRAB criteria”. These criteria include elevated Calcium levels in the blood, Renal (kidney) insufficiency, Anemia (low red blood cell count), and Bone lesions.
The International Myeloma Working Group (IMWG) also includes “myeloma-defining events” (MDEs) in the diagnosis of active multiple myeloma. These MDEs signify a very high risk of progression to symptomatic disease, even in the absence of CRAB criteria. Examples of MDEs include clonal plasma cells in the bone marrow reaching 60% or more, an involved to uninvolved serum free light chain ratio of 100 or greater (with the involved free light chain level being at least 100 mg/L), or more than one focal lesion of at least 5 mm seen on an MRI.
Monitoring Smoldering Myeloma
For most individuals diagnosed with smoldering myeloma, the primary management strategy is “watch and wait” or active surveillance. This involves regular medical check-ups to monitor for signs of disease progression. Monitoring typically includes periodic blood tests, such as serum protein electrophoresis and immunofixation, to track M-protein levels and serum free light chains. Urine tests are also conducted to detect M-protein, and imaging studies like skeletal surveys, MRIs, or PET/CT scans may be performed to assess for bone lesions. These regular assessments, often every two to three months initially, are important for early detection of any changes that might indicate progression to active multiple myeloma. If test results remain stable, the frequency of these checks may decrease over time.
Progression to Active Myeloma
While smoldering myeloma is not active cancer, it can evolve into active multiple myeloma. The annual risk of progression from smoldering multiple myeloma to active multiple myeloma averages around 10% for the first five years after diagnosis. This risk may decrease to 3-5% per year after the initial five-year period. Progression to active myeloma is indicated by the development of symptoms or signs of organ damage, or other myeloma-defining events. The specific risk of progression can vary among individuals, influenced by factors like the level of M-protein, the percentage of plasma cells in the bone marrow, and the serum free light chain ratio.
Treatment Considerations
Generally, individuals with low-risk smoldering myeloma are not treated with anti-myeloma therapy. This is because the potential side effects associated with treatment often outweigh the benefits when there is no active disease causing symptoms or organ damage. The goal is to maintain quality of life without unnecessary medical interventions. For those identified with high-risk smoldering myeloma, treatment might be considered, often within the framework of clinical trials. The aim of such interventions is to delay or prevent the progression to active multiple myeloma. For example, studies have shown that certain therapies, like daratumumab, can reduce the risk of progression in high-risk patients. However, treatment decisions are highly individualized and are made in close consultation with a hematologist or oncologist, weighing the potential benefits against the risks.