Multiple Myeloma

Multiple myeloma is a cancer of plasma cells. The disease most frequently occurs in the marrow of large bones, such as the skull, pelvis and vertebra. In this disease, the malignant cells form tumors which can prevent the marrow from producing healthy red, white, and platelet blood cells. Because plasma cells travel through the body, tumors often occur in several sites simultaneously. Approximately 30,000 people in the United States are diagnosed with multiple myeloma every year.

Risk Factors

Medical research has not conclusively identified the risk factors for developing multiple myeloma. Several common traits have been observed in many multiple myeloma patients, but not all patients with the disease share these risk factors, and only a small minority of people who have these factors ever develop the disease. A preponderance of evidence indicates that these factors are related to development of multiple myeloma:

• Age: People over 65 are much more likely to be diagnosed with multiple myeloma than those under 65. Less than 1% of cases occur in people under 40.
• Gender: 60% of multiple myeloma occurs in men.
• Race: African Americans are twice as likely to develop multiple myeloma as Caucasians. Asian Americans are least likely to develop the disease.
• Family history: Someone with a parent, brother or sister with multiple myeloma has almost four times the likelihood of getting the disease than someone who has no close relatives with the disease.
• Previous history of plasma cell disease: There are two main types of abnormalities of the blood that have a significantly greater chance of developing multiple myeloma.  People who have a condition called, monoclonal gammopathy of undetermined significance (MGUS) is a condition that involves an abnormal protein in the blood.  Solitary plasmacytoma, is an abnormality that involves the bone of other tissues.
• Other Factors: factors suspected, but not proven, to increase the chance of developing multiple myeloma include exposure to radioactivity, working in a petroleum-related industry and obesity.

Warning Signs

The warning signs of multiple myeloma can also be symptoms of other conditions. Most people with these symptoms do not have multiple myeloma. Nevertheless, it is a good idea to consult a doctor to deal with the cause of these symptoms, whatever it may be. Symptoms associated with multiple myeloma include:

• Early onset osteoporosis. This is indicated by increased hunching over of the spine or loss of height.
• Bone pain. The pain is most frequently in the ribs or spine, but it may occur in other bones as well.
• Fatigue.
• Weakness.
• Nausea.
• Vomiting.
• Constipation.
• Loss of appetite.
• Increased thirst.
• Tingling, numbness or burning feeling.
• Unexplained weight loss.
• Frequent urination.
• Unexplained bleeding from the mouth or nose.
• Difficulty concentrating or thinking clearly.

Detection, Diagnosis and Staging

Detection

Multiple myeloma is sometimes detected when abnormalities are seen in a routine blood test or in an x-ray of a broken bone. More frequently it is found when patients consult their doctors about one of the conditions that can be indicators of multiple myeloma or a number of other, non-cancerous conditions.

Diagnosis

• Blood tests. The blood is tested for elevated levels of M-protein, beta-2-microglobulin, calcium and/or immunoglobulins which can indicate multiple myeloma.
• Complete blood count. A sample of blood is analyzed to determine the number and proportion of red blood cells, the number of platelets, the number and type of white blood cells and the amount of hemoglobin in the red blood cells. This helps establish or rule out abnormalities in the cell-producing function of the bone marrow.
• Urine test. This test checks for elevated levels of Bence-Jones protein, a potential indicator of multiple myeloma.
• Biopsy. A sample of bone and marrow is removed (usually from the pelvic bone) under local anesthetic and microscopically examined by a pathologist to detect cancer cells.
• X-ray. Bones are examined for damage and for tumors.

Staging

Some multiple myeloma produces few or no symptoms, and may be stable for years, with no sign of disease progression.

Symptomatic multiple myeloma is the active form of the disease. After diagnosis, the stage of symptomatic multiple myeloma may be determined by one of several key indicators: hemoglobin, M-protein, serum calcium, beta-2-microglobulin or cell counts.

• Stage I: Early stage, only a few myeloma calls are present.
• Stage II: Intermediate stage, moderate level of myeloma cells are present.
• Stage III: Advanced stage, many myeloma cells are present.

In addition to staging, the extent of the spread of the disease is determined at this point.

• Bone densitometry. This test determines which bones have been affected by the disease and the extent of damage to the affected bones.
• X-ray. X-ray images can detect areas and extent of damage.
• MRI. A magnetic resonance imaging scan provides precise images of areas of interest, such as the bone marrow, spinal cord or brain.
• CT. A computed tomography scan with contrast agent provides a precise structural image of swollen lymph nodes.
• PET. A positron emission tomography scan detects unusual metabolic activity at a molecular level to find cancer undetectable by other methods.
• PET-CT. A combined PET and CT scan can simultaneously find microscopic cancers, determine how aggressive they are and locate them precisely.

Additional tests which may or may not be indicated in specific instances include:

• Chromosome analysis. This indicates prognosis and can help determine the treatments most likely to be effective.
• Plasma morphology. This test determines the maturity of malignant plasma cells, which is an indicator of how aggressive the cancer is.
• Bone marrow microvessel density. The level of new blood vessel development indicates how vigorously the cancer is growing.

Treatment

Watchful waiting

Patients with abnormal plasma cells but no symptoms of multiple myeloma can be stable for years without progressing to active multiple myeloma. In some cases the active form of the disease never develops. In these cases, no treatment is needed. Patients must be monitored closely so any progression to active multiple myeloma can be caught and treated early.

Chemotherapy

Chemotherapy attacks multiple myeloma with drugs that either kill cancer cells or stop them from dividing, or with drugs that prevent the growth of new blood vessels needed to sustain a tumor. Chemotherapies for multiple myeloma include:

• High-dose corticosteroids.
• Thalidomide.
• Lenalidomide.
• Bortezomib.

Radiation therapy

Radiation therapy attacks cancer cells with X-ray or other radiation beams directed at the tumor. IMRT (intensity modulated radiation therapy) shapes the beam of radiation to the contours of the tissue to avoid unnecessarily radiating other areas of the body. TomoTherapy is the latest advance in radiation therapy for spinal tumors, often found in multiple myeloma. This technology combines a CT scanner and helical-pattern IMRT beam in one machine to precisely map tumors and provide a maximum dose to the lesion with minimal side effects on surrounding healthy tissue.

Other therapies

Chemotherapy and radiation therapy either alone, together or in combination with stem cell transplantation, are the most frequent treatments for multiple myeloma. In some cases, other treatments may also be used.

• Surgery. Because of the widespread nature of multiple myeloma, surgery is not often used in the treatment of the disease, but in some instances it is advisable to remove tumors surgically. When surgery is indicated, it is always done in conjunction with radiation therapy and/or chemotherapy.
• Biologic therapy. Substances made in the body, or made in a laboratory to mimic the function of those made in the body, can be used to attack multiple myeloma cells. This treatment, also called immunotherapy, increases the body’s natural defenses against the cancer cells.
• Plasmapheresis. In plasmapheresis, blood is removed from the body, the plasma filtered out and the remaining blood and healthy replacement plasma are put back into the body. Although this treatment removes malignant plasma cells, it does not prevent new malignant cells from forming.