Smoldering multiple myeloma (SMM) is a condition characterized by the presence of abnormal plasma cells in the bone marrow or abnormal proteins in the blood or urine, without causing any noticeable symptoms or organ damage. It is considered a pre-cancerous state, meaning it can progress to active multiple myeloma, a more serious blood cancer. While SMM is a significant diagnosis, it does not immediately threaten life. This article will explore whether SMM always progresses to active multiple myeloma and what this means for individuals diagnosed with the condition.
Understanding Smoldering Myeloma
Smoldering multiple myeloma is defined by specific laboratory findings, including a certain amount of monoclonal protein (M-protein) in the blood or urine, or a percentage of abnormal plasma cells in the bone marrow. Individuals with SMM do not experience symptoms like bone pain, fatigue, or kidney problems. This absence of symptoms and organ damage distinguishes it from active multiple myeloma.
Active multiple myeloma is diagnosed when certain criteria, collectively known as CRAB criteria, are present. These include elevated calcium levels (Hypercalcemia), kidney dysfunction (Renal failure), low red blood cell count (Anemia), or bone lesions (Bone lesions). In SMM, these signs of organ damage are absent. SMM is a precursor condition, distinct from the symptomatic disease.
The Likelihood of Progression
Smoldering multiple myeloma does not always progress to active multiple myeloma. Many individuals with SMM may live for years without developing the active disease, and some may never progress. The risk of progression is highest shortly after diagnosis, typically around 10% to 15% per year for the first five years.
After this initial period, the annual risk of progression generally decreases. For instance, the risk can drop to about 3% per year between years three and ten, and further reduce to approximately 1% per year thereafter. This variability highlights that SMM is a heterogeneous condition.
Factors That Influence Progression
Several factors help predict the likelihood of SMM progressing to active multiple myeloma. The amount of M-protein in the blood, the percentage of abnormal plasma cells in the bone marrow, and the free light chain ratio are important indicators. Higher levels of M-protein or a greater percentage of plasma cells correlate with an increased risk of progression.
Genetic abnormalities within the plasma cells also play a role in predicting progression. Specific chromosomal changes, such as certain translocations or deletions, can indicate a higher risk. Risk stratification models, like the International Myeloma Working Group (IMWG) 2/20/20 model, combine these factors to categorize SMM into low, intermediate, or high-risk groups.
How Progression is Monitored
Regular monitoring is an important part of managing smoldering multiple myeloma to detect any signs of progression early. This involves periodic blood and urine tests to measure M-protein levels and free light chains. These tests help track the activity of the abnormal plasma cells and can indicate changes over time.
Imaging studies are also used to check for bone damage, a common sign of active multiple myeloma. Bone marrow biopsies might be performed at diagnosis and potentially repeated if there are significant changes in other test results or new symptoms. Regular follow-up appointments with a hematologist or oncologist are important for reviewing results and assessing overall health.
Management Approaches for SMM
For many individuals with smoldering multiple myeloma, especially those in low- and intermediate-risk categories, the standard management approach is “watch and wait,” also known as active surveillance. This involves close monitoring without immediate treatment, as the benefits of early intervention may not outweigh potential side effects. The goal is to avoid unnecessary treatment until it is truly needed.
For individuals with high-risk SMM, there is ongoing research into early intervention strategies. Clinical trials are exploring whether active treatment can delay or prevent progression to symptomatic multiple myeloma in this specific group. While some promising results have emerged from these trials, early treatment for high-risk SMM is not yet a standard practice and is often considered within the context of a clinical study.