Smoldering Myeloma

• Smoldering Myeloma is an asymptomatic precursor to Multiple Myeloma.
• It is diagnosed by specific blood and bone marrow findings without end-organ damage.
• Patients are typically monitored closely due to a variable risk of progression.
• Active treatment is often deferred, with a focus on surveillance, unless it’s high-risk or part of a clinical trial.

What is Smoldering Myeloma?

Smoldering Myeloma (SMM) is an asymptomatic plasma cell disorder that serves as an intermediate stage between Monoclonal Gammopathy of Undetermined Significance (MGUS) and active Multiple Myeloma. Individuals with SMM have a higher number of abnormal plasma cells in their bone marrow (typically 10-60%) and/or a higher level of M-protein in their blood or urine compared to MGUS, but they do not exhibit any of the “CRAB” criteria (elevated calcium, renal failure, anemia, or bone lesions) that define active Multiple Myeloma. This lack of end-organ damage is a crucial distinguishing factor, meaning the condition is not yet causing significant health problems.

The diagnosis of Smoldering Myeloma is made through a combination of blood tests, urine tests, and a bone marrow biopsy. It is essential to differentiate SMM from MGUS, which has a lower risk of progression, and from active Multiple Myeloma, which requires immediate treatment. The presence of these abnormal cells indicates a potential for progression, making careful monitoring vital for affected individuals.

Smoldering Myeloma Symptoms and Outlook

A defining characteristic of Smoldering Myeloma is the absence of symptoms. Individuals with SMM typically do not experience any pain, fatigue, kidney problems, or bone issues, which are common in active Multiple Myeloma. This is why the condition is often discovered incidentally during routine blood tests performed for other reasons, such as a routine physical examination or evaluation for unrelated health concerns. The lack of smoldering myeloma symptoms underscores the importance of diagnostic testing to identify the condition.

The smoldering myeloma prognosis is highly variable. Some individuals may live for many years without progressing to active Multiple Myeloma, while others may progress more quickly. The risk of progression is not uniform and depends on several factors, including the percentage of plasma cells in the bone marrow, the level of M-protein, and the ratio of free light chains in the blood. Patients are often stratified into low-risk, intermediate-risk, and high-risk categories based on these factors, with high-risk SMM having a greater likelihood of progressing to active disease within a few years. Regular follow-up is crucial to monitor for any signs of progression.

Smoldering Multiple Myeloma Treatment and Monitoring

For most individuals with Smoldering Myeloma, particularly those in the low-risk category, active treatment is generally not recommended immediately. Instead, the standard approach is “watch and wait” or active surveillance. This involves regular monitoring through blood tests, urine tests, and sometimes imaging studies or repeat bone marrow biopsies to detect any signs of progression to active Multiple Myeloma. The goal of this monitoring is to identify progression early, allowing for timely intervention when treatment becomes necessary.

For individuals classified as high-risk SMM, there may be discussions about participating in clinical trials that investigate early intervention strategies. These trials aim to determine if treating high-risk SMM before it progresses to active Multiple Myeloma can delay or prevent the onset of symptomatic disease. However, outside of clinical trials, the primary focus remains on surveillance. If progression to active Multiple Myeloma occurs, the smoldering multiple myeloma treatment options are the same as those used for newly diagnosed active Multiple Myeloma, which may include chemotherapy, immunomodulatory drugs, proteasome inhibitors, and potentially stem cell transplantation.