Smouldering myeloma is a pre-cancerous condition involving abnormalities in plasma cells, a type of white blood cell produced in the bone marrow. It represents an early stage within a spectrum of plasma cell disorders. Individuals with smouldering myeloma typically do not experience symptoms, and it is often referred to as asymptomatic myeloma. It signifies the presence of abnormal cells and proteins without causing damage to the body’s organs or tissues.
Understanding Smouldering Myeloma
Smouldering myeloma is characterized by an abnormal accumulation of plasma cells in the bone marrow and the presence of a monoclonal protein, also known as M-protein, in the blood or urine. These abnormal plasma cells are a type of B lymphocyte that produce antibodies to fight infections. In smouldering myeloma, however, these cells become abnormal and produce a non-functional M-protein.
The condition often goes unnoticed because it does not cause symptoms. It is frequently discovered incidentally during routine blood tests performed for other health concerns, which may reveal elevated protein levels and prompt further investigation.
To diagnose smouldering myeloma, specific criteria outlined by the International Myeloma Working Group (IMWG) must be met. These include a serum M-protein level of 3 grams per deciliter (g/dL) or higher, or a urinary M-protein level of 500 milligrams per 24 hours or more. Additionally, bone marrow biopsy findings must show that clonal plasma cells constitute between 10% and 60% of the cells in the bone marrow. A diagnosis also requires the absence of any myeloma-defining events, such as organ damage.
Distinguishing Smouldering Myeloma from Related Conditions
Smouldering myeloma exists within a continuum of plasma cell disorders, which also include Monoclonal Gammopathy of Undetermined Significance (MGUS) and active Multiple Myeloma. MGUS is considered the earliest stage and a benign precursor condition. Individuals with MGUS have lower levels of M-protein in their blood or urine, less than 3 g/dL, and less than 10% monoclonal plasma cells in their bone marrow. The risk of MGUS progressing to active myeloma is low, around 1% per year.
Smouldering myeloma represents an intermediate stage between MGUS and active multiple myeloma, characterized by higher levels of abnormal plasma cells and M-protein than MGUS, but still without symptoms or organ damage. The absence of organ damage, as defined by the CRAB criteria, is a key differentiating factor for both MGUS and smouldering myeloma.
In contrast, active Multiple Myeloma is a symptomatic cancer characterized by significant organ damage. The presence of “myeloma-defining events” indicates active myeloma, often summarized by the CRAB criteria: high Calcium levels in the blood, Renal (kidney) insufficiency, Anemia (low red blood cell count), and Bone lesions. When these symptoms or organ damage are present, a diagnosis of active multiple myeloma is made, requiring immediate treatment.
Progression Risk and Management
While smouldering myeloma is a pre-cancerous condition, not all individuals with this diagnosis will progress to active multiple myeloma. The average risk of progression is approximately 10% per year for the first five years following diagnosis. After this initial period, the risk typically decreases to about 3% per year for the next five years, and then to around 1% per year thereafter.
Doctors assess the risk of progression by evaluating several factors. Higher M-protein levels, particularly above 3 g/dL, and a higher percentage of plasma cells in the bone marrow (e.g., over 20%) are associated with increased risk. Certain genetic abnormalities, identified through tests like FISH studies, can also indicate a higher likelihood of progression. An elevated ratio of involved to uninvolved free light chains in the blood, especially a ratio of 100 or greater, is another significant risk factor.
For most individuals with smouldering myeloma, the standard approach is “watch and wait,” also known as active surveillance. Immediate treatment is generally not recommended because the potential side effects of therapy often outweigh the benefits for asymptomatic patients. The goal is to closely monitor the condition for any signs of progression to active multiple myeloma, allowing for timely intervention if changes occur.
Monitoring involves regular blood and urine tests every three to six months, especially during the first year, to track M-protein levels, kidney function, calcium levels, and red blood cell counts. Imaging studies, such as whole-body MRI or PET/CT scans, may also be performed to check for bone lesions. If test results remain stable after a year, evaluations may be extended to every 6 to 12 months. Clinical trials are actively exploring new treatment options for high-risk smouldering myeloma, with some studies showing promise in delaying progression in certain patient groups.