Multiple Myeloma

Multiple myeloma facts
  • Multiple myeloma is a cancer of the plasma cells in the bone marrow.
  • The cause of multiple myeloma is not known.
  • Risk factors for multiple myeloma have not been established although researchers have suggested genetic abnormalities, such as c-Myc genes or environmental exposures, may play a role.
  • Symptoms and signs of multiple myeloma include:

  1. anemia,
  2. bone tenderness,
  3. bone pain,
  4. weakness,
  5. bone fractures,
  6. kidney damage,
  7. hypercalcemia,
  8. nerve damage,
  9. skin lesions,
  10. enlarged tongue, and
  11. infections.

  • Multiple myeloma is diagnosed with a bone marrow aspiration and/or biopsy. Other tests include blood monoclonal immunoglobulin and radiology tests to determine the extent of bone lesions.
  • Although there are several staging systems, stages I, II, and III usually represent multiple myeloma with increasing severity of disease.
  • Treatment for multiple myeloma includes drugs that modulate the immune system, chemotherapy drugs, radiation therapy, stem cell transplants and, in some patients, surgery.
  • Although the patient's primary care physician is involved in organizing treatments, specialists who treat multiple myeloma include oncologists, hematologists, radiologists, experts in stem cell transplantation and orthopedic and/or spine surgeons.
  • The prognosis for myeloma is only fair. Median survival is about three years, but some patients have a life expectancy of 10 years.
  • The International Myeloma Foundation can provide further support for myeloma patients.
What is multiple myeloma? What are plasma cells?
Multiple myeloma definition
Multiple myeloma is a type of cancer of the plasma cells of the bone marrow. These are protein-making cells that normally make all of the different kinds of antibodies of the immune system. In multiple myeloma, the plasma cells undergo what is referred to as a malignant transformation and become cancerous. These myeloma cells stop making different forms of protein in response to the immune system's needs and instead start to produce a single abnormal type of protein, a monoclonal or M protein. Multiple myeloma plasma cell populations accumulate in the bone marrow and these collections of cells called plasmacytomas can erode the hard outer shell or cortex of the bone that normally surrounds the marrow. These weakened bones show thinning of the bone such as is seen in nonmalignant osteoporosis or what appear to be punched out or lytic bone lesions. These lesions may cause pain and even breaks or fractures of the weakened bones. They may cause other systemic problems listed below. Multiple myeloma is often referred to simply as myeloma (also termed Kahler's disease after the physician who first described this cancer). The disease usually occurs in people past middle-age. However, rarely it is possible to occur in a child.

What causes multiple myeloma?
What triggers the malignancy of plasma cells in multiple myeloma is not known. The cancerous myeloma plasma cells proliferate and crowd out normal plasma cells and can etch away areas of bones. The proteins produced in large amounts can cause many of the symptoms of the disease by making the blood more thickened (viscous) and depositing the proteins in organs that can interfere with the functions of the kidneys, nerves, and immune system.

What are risk factors for multiple myeloma? Is multiple myeloma hereditary?
The definitive cause of multiple myeloma has not been established, but research has suggested several factors may be risk factors or contribute to multiple myeloma development in an individual. A genetic abnormality such as c-myc oncogenes and others have been associated with multiple myeloma development. Currently, there is no evidence that heredity plays a role in multiple myeloma development so it is not considered to be a hereditary disease. Environmental exposures to herbicides, insecticides, benzene, hair dyes, and radiation have been suggested as causes but definitive data is lacking. Inflammation and infection have been suggested but again not proven to cause multiple myeloma. However, a benign proliferation of a plasma cell can result in a situation where a monoclonal antibody is produced in high amounts (but not as high as seen with multiple myeloma). This result is termed monoclonal gammopathy of unknown or undetermined significance (abbreviated as MGUS). About 19% of MGUS patients develop multiple myeloma in about two to 19 years after MGUS diagnosis. In addition, smoldering multiple myeloma (also termed inactive) is an early precursor to multiple myeloma. Abnormal proteins in blood or urine are detectable with special testing before multiple myeloma symptoms occur.

What are multiple myeloma symptoms and signs?
Patients with myeloma may be found asymptomatic with an unexplained increase in protein in the blood. With more advanced disease, some myeloma patients may present with weakness due to anemia caused by inadequate production of red blood cells, with bone pain due to the aforementioned bone damage, and as the abnormal M protein can accumulate in and damage the kidneys thereby resulting in a patient being found to have otherwise unexplained kidney damage and decreased kidney function.

The following is a list symptoms and signs of multiple myeloma:
  • Anemia
  • Bleeding
  • Nerve damage
  • Skin lesions (rash)
  • Enlarged tongue (macroglossia)
  • Bone tenderness or pain, including back pain
  • Weakness, fatigue or tiredness
  • Infections
  • Pathologic bone fractures
  • Back pain
  • Spinal cord compression
  • Kidney failure and/or damage
  • Loss of appetite and weight loss
  • Constipation
  • Hypercalcemia
  • Leg swelling
What tests do health care professionals use to make a diagnosis of multiple myeloma?
In many patients, multiple myeloma is first suspected when a routine blood test shows an abnormal amount of protein in the bloodstream or an unusual stickiness of red blood cells causing them to stack up almost like coins in a pattern called rouleaux, an unusual formation for red blood cells. The health care professional will do a history and physical exam, looking for signs and symptoms (see above) of multiple myeloma. If multiple myeloma is suspected, several studies help confirm the diagnosis. They include a bone marrow aspiration and biopsy most commonly from the large bones of the pelvis. Cells obtained from the marrow are studied by a pathologist to determine if there is one (plasmacytoma) or more (multiple myeloma) abnormal types or numbers of cells. A sample of the bone marrow aspirate is also studied for more detailed characteristics such as the presence or absence of abnormal numbers or types of chromosomes (DNA) by what is called cytogenetic testing. Other molecular testing may be done on the marrow sample as well. The bone marrow biopsy can assess the concentrations of cells in the marrow and the presence of abnormal invasive growth of cellular elements. Blood testing and urine testing by several methods can determine levels and types of monoclonal protein produced. The M protein may be a complete form of a type of antibody called an immunoglobulin (IgG or IgA, for example) or only a portion of the protein called a lambda or kappa light chain. Normal antibodies consist of both heavy and light chain components. In 2011, the National Comprehensive Cancer Network (NCCN) recommended that a serum free light chain assay and fluorescence in situ hybridization (FISH) test be used to further identify multiple myeloma in patients. Most clinicians will use X-ray studies to identify skeletal lesions and MRI for spinal, paraspinal, or spinal cord lesions in multiple myeloma. In addition, several routine tests (CBC, sedimentation rate, BUN, C-reactive protein, and others) are also done.