Smoldering Multiple Myeloma
Smoldering multiple myeloma (SMM) is a bone marrow and blood condition that has the potential to develop into an uncommon blood cancer active multiple myeloma. It may take some years for smoldering multiple myeloma to become active multiple myeloma. Smoldering multiple myeloma (SMM) acts as a precursor or pointer to the possible development of multiple… Read More
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Smoldering Multiple Myeloma
Smoldering multiple myeloma (SMM) is a bone marrow and blood condition that has the potential to develop into an uncommon blood cancer active multiple myeloma. It may take some years for smoldering multiple myeloma to become active multiple myeloma. Smoldering multiple myeloma (SMM) acts as a precursor or pointer to the possible development of multiple myeloma (MM). It occurs as a result of the mutation of certain white blood cells.
Smoldering multiple myeloma is comparable to monoclonal gammopathy of undetermined significance (MGUS). Individuals with both diseases are likely to develop Active multiple myeloma. However, SMM has a higher chance of progressing to MM than MGUS. Both diseases are not regarded and treated as cancer but may become malignant with time.
Causes and Predisposing Factors of Smoldering Multiple Myeloma
The presence of high numbers of abnormal plasma cells in the bone marrow and a high level of a specific type of protein called M protein in the blood and urine is a major pointer to SMM. However, research cannot provide a specific cause for this occurrence.
Factors that increase the chances of diagnosis are:
- Age: Individuals that are over age 60 a most commonly affected. It often develops between 50 and 70. Between 62 and 67 years old is the average age at diagnosis.
- Genetic mutations: Researchers are looking into the relationship between multiple myeloma and smoldering multiple myeloma and oncogene mutations or changes (cells that promote growth). People with certain gene mutations may produce a higher number of plasma cells in the blood. The defective gene may switch on this process. This deleterious gene can be inherited.
- Obesity: Obesity is defined as having a high body fat percentage. Research has shown that overweight and obese individuals are more likely to develop SMM.
- Gender: Men are slightly more likely to get smoldering multiple myeloma than women.
- Race: Research has shown that blacks are twice as likely to develop smoldering multiple myeloma than whites.
Clinical Signs and Symptoms of Smoldering Multiple Myeloma
Smoldering multiple myeloma causes changes such as:
- Increase in the levels of monoclonal protein (M protein) in the blood (usually 3g/dl or above).
- Increase in the levels of plasma cells in the bone marrow, where (about 20% to 60%)
- Peripheral neuropathy, which leads to numb or tingling hands and feet.
- Osteoporosis, or brittle bones
- Infections
- Bone pain
- Fatigue and general weakness
- Problems with balance
- Confusion and dizziness
- Kidney problems
Classifications of Smoldering Multiple Myeloma
There are two major models used for the classification of smoldering multiple myeloma. These models are based on the risk of SMM progressing to multiple myeloma. A person’s risk level could be low, moderate, or high. The two models are:
- The Mayo Clinic model: This model examines the quantity of light chains and M-proteins produced by plasma cells and unusual cells, respectively. These plasma cell proteins can be free light chains or they can join with another form of plasma proteins known as heavy chains to form antibodies. The Mayo Clinic model examines the ratio between the two forms of serum-free light chains. The result can then be categorized as low-risk individuals i.e., individuals with no risk factors; intermediate-risk individuals i.e., individuals with one risk factor; and high-risk individuals i.e., individuals with two to three risk factors. The risk factors considered for the Mayo Clinic model include creatinine level, age, decreased hemoglobin level, light-chain type, etc.
- The Spanish model: The Spanish model, unlike the Mayo Clinic model, looks only for high-risk individuals instead of categorizing them into different risk levels. The Spanish model looks at the proportion of abnormal bone marrow plasma cells and then if someone has a noticeable reduction in specific antibodies.
How to Diagnose Smoldering Multiple Myeloma
Several tests can be conducted to determine the status of an individual suspected to have SMM. The first indicator of smoldering multiple myeloma may be routine testing that reveals M protein in urine and blood. If there are indications that an individual has SMM, further tests may be done to ensure that it is not progressing to active multiple myeloma. The tests conducted include:
- Complete blood count (CBC): This test measures the red and white blood cell numbers and platelet counts that the bone marrow produces.
- Urine assay: This is done to check for M proteins (immune proteins) and total protein in the urine.
- Blood chemistry test: This test shows your creatinine, albumin, and calcium levels. This helps to assess the liver and kidney functions.
- X-rays: X-rays are used to check signs of bone damage seen in cases of SMM.
- Computed tomography (CT) scan: The use of a computed tomography (CT) scan is another method for detecting bone deterioration.
- Magnetic resonance imaging (MRI): Using radio waves and powerful magnets, magnetic resonance imaging (MRI) produces precise images of your bones and spine. This is used to check for bone damage.
- Quantitative immunoglobulin test: It measures the quantity of immunological proteins (M proteins) in the blood.
- Electrophoresis and serum immunofixation: These tests look for M proteins (immune proteins) in the blood.
- Bone marrow biopsies: Bone marrow biopsies are used to analyze the percentage of normal and abnormal plasma cells in your bone marrow. They can also be used to detect DNA changes that can lead to cancer.
Differential Diagnosis for SMM
- Monoclonal gammopathy of undetermined significance (MGUS): SMM can be confused with MGUS. SMM is distinguished from monoclonal gammopathy of undetermined significance (MGUS) based on the size of the M protein and the percentage of plasma cells in the bone marrow.
- Multiple myeloma (MM): The difference is based on the lack of myeloma-defining events seen in SMM.
What is the Treatment for Smoldering Multiple Myeloma?
There is currently no single recommended treatment for multiple myeloma. Health professionals do a “Watchful waiting”. During this period, the M protein levels and levels of plasma cells in the bone marrow are routinely monitored. For individuals with an intermediate or high risk of developing MM, some medical practitioners commence MM treatment as soon as SMM diagnosis is made.
Drugs that may slow the development of MM such as lenalidomide have been used successfully during clinical trials. Other trial drugs include Daratumumab, isatuximab, and Pembrolizumab. Supportive care and improvements in lifestyle are also recommended as part of activities that may help the diagnosis.
Conclusions
Individuals are highly encouraged to participate in clinical trials to improve on existing results. This is to determine the best course of action to be taken for patients. However, the standard approach to management is the close observation of the individual irrespective of risk status.