Multiple myeloma is the second most common blood cancer, with substantial morbidity and mortality. According to Globocan 2018, about 159,985 new cases were diagnosed, and the disease was responsible for 106, 105 deaths globally.
Multiple myeloma refers to the cancer of plasma cells, a type of white blood cells predominantly found in bone marrow and lymph nodes. They secrete large quantities of proteins, known as antibodies, against pathogens or the toxins released by them.
Our immune system is made up of several types of cells that defend our body against potent pathogens. B cells are one of the subtypes of the lymphocytes, a major type of white blood cells (WBC’s). During any infection, the B cells differentiate into plasma cells that make antibodies to fight against pathogens. Plasma cells are predominantly found in the bone marrow, a soft-tissue inside bones, acting as a source for red blood cells (RBC), white blood cells (WBC), and platelets.
During multiple myeloma, the plasma cells become cancerous, and grow uncontrollably to build up in bone marrow and crowd out the healthy cells. These plasma cells make abnormal protein known as M protein, higher levels of which can lead to many complications. High level of M protein in the blood is also noted as a hallmark of multiple myeloma.
Multiple myeloma is not limited to a specific bone or location within the bone, but is likely to involve the entire skeleton. However, when only one single lesion occurs, it is known as plasmacytoma.
Causes of multiple myeloma
The exact cause for multiple myeloma is unknown, however there are some known risk factors for multiple myeloma that increases one’s risk for developing the condition. These include:
- Age over 65 years
- Being male
- Having family history of myeloma
- Being obese
- Having other plasma cell neoplasms such as monoclonal gammopathy of undetermined significance (MGUS) or solitary plasmacytoma
- Exposure to ionizing radiation, asbestos, benzene, pesticides etc
- Being infected with HIV or human herpesvirus 8
Multiple myeloma develops slowly, and the symptoms may not appear until later stages. The symptoms, when they occur may, vary depending on the tumor location and the type of blood cells affected. These may include:
- Bone pain, especially in your spine, hips, or chest
- Shortness of breath
- Nausea and vomiting
- Loss of appetite
- Unintentional weight loss
- Confusion or mental fogginess or confusion
- Recurrent infections or illnesses
- Frequent urination
- Weakness and numbness in legs
- Excessive thirst
In many cases, multiple myeloma could be detected accidentally during the routine blood or urine tests. In other cases, when any sign and symptom suggest multiple myeloma, the following tests or procedures may be used to confirm the diagnosis.
Blood tests: Blood tests are used to identify the blood cell counts, calcium and uric acid levels, M proteins, or other abnormal proteins like beta-2-microglobulin. Blood viscosity may be measured, as the blood may turn too thick due to the accumulation of excess protein. Measuring the levels of lactic dehydrogenase (LDH) may also help to evaluate the prognosis of the condition; high levels of LDH indicates advanced disease with poor prognosis.
Urine tests: Urine samples are analyzed for the presence of M proteins that are referred as Bence Jones proteins when detected in urine. However, routine urinalysis may not indicate the presence of Bence Jones proteinuria. Hence a 24-hour urinalysis (a sample of urine that has been collected over a 24-hour period), urine protein electrophoresis (UPEP) and urine immunofixation may be required.
Bone marrow aspiration: During a bone marrow aspiration, a bone marrow sample is obtained using a long needle inserted into the bone. The sample is sent for laboratory analysis to check for the presence of myeloma cells. Specialized molecular tests such as fluorescence in situ hybridization (FISH) can be used to detect genetic abnormalities related to multiple myeloma.
Imaging tests: The following imaging tests can be used to reveal bone problems associated with multiple myeloma and to determine the extent of cancer spread.
- Bone X-rays: Damage to the bones caused by myeloma cells can be detected using X-rays. A series of X-rays known as bone survey or skeletal survey to include majority of the bones (skull, spine, arms, ribs, hips, and thighs) is performed to reveal presence of any bone destruction.
- Computed Tomography (CT) Scan: A CT scan provides detailed cross-sectional images of the bones or organs using X-rays, and can help detect the bone damage due to myeloma. It may also be used to guide the biopsy needle to obtain tissue sample from the suspicious area.
- Magnetic resonance imaging (MRI): MRI uses radiowaves to obtain detailed images of the soft tissues and bones in the body, which can reveal abnormalities in the bone marrow. MRI can also reveal plasmacytoma that cannot be seen using regular X-rays.
- Positron emission tomography (PET): A PET scan is performed by injecting a radioactive tracer into the body, which is mainly absorbed by the cancer cells. A special camera is used to create a picture of the areas of radioactivity in the body. A PET scan is often combined with a CT scan to provide more detailed and accurate information about the cancer. Like an MRI, a PET scan can help detect plasmacytomas that cannot be seen on regular x-rays.
Stages of multiple myeloma
The information obtained from the diagnostic tests is used to analyze the extent of the cancer spread. This process is known as staging. It helps to understand the outlook of the condition and work-up the treatment plan.
The staging of multiple myeloma is based on the measurement of serum albumin and the levels of serum beta-2-microglobulin (β2-M).
- Stage I: Serum beta-2 microglobulin is less than 3.5 mg/L with serum albumin of 3.5 g/dL or more
- Stage II: Serum beta-2 microglobulin between 3.5 mg/L and 5.5 mg/L and serum albumin less than 3.5 g/dL
- Stage III: Serum beta-2 microglobulin greater than 5.5 mg/L
Treatment for multiple myeloma predominantly involves managing the symptoms such as pain, controlling complications and slowing down the progression of the condition. Many treatment options are available for multiple myeloma, which are selected based on extent of the condition and how it affects your body.
The standard treatments options for multiple myeloma include:
Targeted therapy: Targeted therapy is rather a primary therapy used to treat all stages of multiple myeloma. The drugs in this class known as proteasome inhibitors block the action of proteasomes, which are substances that break down old proteins, eliminate them and replace them with new ones. This causes accumulation of large amounts of protein leading to death of cancer cells.
Immunomodulatory drugs: Immunotherapy drugs are used in the standard treatment of multiple myeloma. They act by strengthening the immune cells to fight against cancer cells and preventing the growth signals of the cancer cells, thereby directly killing the myeloma cells.
Corticosteroids: Corticosteroids are used to treat all the stages of multiple myeloma. They can help control inflammation and can also kill multiple myeloma cells, when used in high doses. They may also help to reduce nausea and vomiting associated with the chemotherapy and other treatments.
Monoclonal antibodies: Monoclonal antibodies are specifically designed to target specific proteins present on the myeloma cells, thereby killing them.
Chemotherapy: Chemotherapy involves the use of drugs that act on fast-growing cells, thus affecting the cancer cells and killing them. These drugs can affect the normal cells and hence chemo drugs are given in cycles, which allows the normal cells to recover from the damage. In the treatment of multiple myeloma, drugs are frequently used in high doses prior to a bone marrow transplant. Chemotherapy drugs are usually given in combination.
Radiation therapy: Radiation therapy involves using high-energy beams (X-rays or protons) to damage cancer cells and prevent their growth. It is used to treat specific cases of multiple myeloma or to reduce its complications. High doses of radiation along with chemotherapy may be used in the treatment of plasmacytomas, whereas, low doses may be used to relieve symptoms such as pain or to prevent bone fractures and spinal cord compression.
Stem cell transplant
Stem cell transplant is commonly used to treat multiple myeloma. Initially, a high-dose chemotherapy is used to kill the affected cells in bone marrow followed by infusing the healthy stem cells into the body, which travels to the bones and rebuilds the bone marrow. When the patient receives his own stem cells it is known as autologous stem cell transplant. When the stem cells are obtained from the donor, it is called as allogeneic stem cell transplant.
Although many factors may affect the prognosis of multiple myeloma, it can be well-managed. The five-year relative survival for multiple myeloma is about 60%. The survival rate for multiple myeloma is improving, which can be attributed to the continuous research towards the development of new drugs and their approval.
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