Multiple Myeloma

Multiple myeloma is an incurable but treatable disease.  Also known as myeloma or plasma cell myeloma, it is a hematologic cancer, meaning it develops in the blood.  It is a cancer of the plasma cell, an important part of the immune system that produces immunoglobulins (antibodies) to help fight infection and disease.

As tumors grow inside the bone marrow, they invade the hard, outer part of the bone.  In most cases, the myeloma cells spread into the cavities of all the large bones of the body, forming multiple small lesions.  Hence the name "multiple" myeloma.  In some cases, however, the myeloma cells collect in a single bone and form a tumor called plasmacytoma.

A patient's myeloma is often referred to by the type of immunoglobulin or light chain (kappa or lambda type) produced by the cancerous plasma cell.  The frequency of the various immunoglobulin types of myeloma parallels the normal serum concentrations of the immunoglobulins.  The most common myeloma types are IgG and IgA.  IgG myeloma accounts for about 60-70% of all cases of myeloma and IgA accounts for about 20% of cases.  Few cases of IgD and IgE myeloma have been reported.

Incidence; Contributing Risk Factors

Multiple myeloma is the second most prevalent blood cancer after non-Hodgkin's lymphoma.  It represents approximately 1% of all cancers and 2% of all cancer deaths.  Although the peak age of onset of multiple myeloma is 65 to 70 years of age, recent statistics indicate both increasing incidence and earlier age of onset.  At the time of writing, there are approximately 45,000 people in the United States living with multiple myeloma and an estimated 14,600 new cases of multiple myeloma are diagnosed each year.

Multiple myeloma affects slightly more men than women.  African Americans and Native Pacific Islanders have the highest reported incidence of this disease and Asians the lowest.  Results of a recent study found the incidence of myeloma to be 9.5 cases per 100,000 African Americans and 4.1 cases per 100,000 Caucasian Americans.  Among African Americans, myeloma is one of the top 10 leading causes of cancer death.

Agricultural occupations, petroleum workers, workers in leather industries, and cosmetologists with exposure to herbicides, insecticides, petroleum products, heavy metals, plastics, and various dusts, including asbestos, seem to have a higher-than-average chance of multiple myeloma.  In addition, individuals exposed to large amounts of radiation are at increased risk for myeloma.

Signs and Symptoms

There are often no symptoms in the early stages of myeloma.  In some cases, myeloma may be discovered by accident during routine blood testing.  When present, symptoms may be vague and similar to those of other conditions.  Here are possible symptoms; rarely does one patient have all of them:

• Kidney problems – Excess protein in the blood, which is filtered through the kidneys, can cause kidney damage and lead to renal failure.  Increased calcium in the blood (hypercalcemia) overworks the kidneys and can cause a variety of symptoms, including loss of appetite, fatigue, muscle weakness, restlessness, difficulty in thinking or confusion, constipation, increased thirst, increased urine production, and nausea and vomiting.
• Pain – A common early symptom of multiple myeloma is pain in the lower back or in the ribs.  This is the result of tiny fractures in the bones caused by accumulation of plasma cells and weakened bone structures.
• Fatigue – As the number of malignant plasma cells increases in the bone marrow, the growth and development of red blood cells in the bone marrow may be suppressed, leading to low levels of red blood cells in the blood (anemia).  Anemia can result in unusual tiredness and abnormal paleness.
• Recurrent infection – Increased numbers of myeloma cells can also decrease the production of infection-fighting white blood cells, leading to reduced immunity and the possibility of frequent recurrent infections, such as bacterial pneumonia, urinary-tract infections, and shingles.

Much less frequent symptoms with multiple myeloma are related to complications that may occur with the disease.  These complications include:

• Hyperviscosity syndrome, which occurs when the protein concentration in the blood becomes very high and the blood becomes very thick and sticky.  Signs and symptoms of hyperviscosity are shortness of breath, confusion, and chest pain.
• Cryoglobulinemia, which may occur when the paraprotein is of a specific type that comes out of solution as particles when exposed to cold temperatures.  These particles may block small blood vessels and cause symptoms such as pain and numbness in the fingers and toes in cold weather.
• Amyloidosis is a rare complication that occurs more often in patients whose plasma cells produce only light chains.  Light chains can combine with other serum proteins to produce amyloid protein, a starch-like substance.  The amyloid protein may be deposited in various tissues and organs, including the kidneys, liver, and heart, and disrupt their normal functions.  Also, amyloid protein can stick to the walls of blood vessels, causing them to lose their elasticity and make it difficult to maintain blood pressure.  Symptoms of amyloidosis may include low blood pressure and kidney, heart, or liver failure.  Amyloidosis is a disease that also occurs in individuals who do not have multiple myeloma.

Diagnosis and Tests

The diagnosis of multiple myeloma is often made incidentally during routine blood tests for other conditions.  For example, the existence of anemia and a high serum protein may suggest further testing.

A diagnosis of myeloma is made based on the presence of an increased number of plasma cells in the bone marrow and, in most cases, the presence of excess protein (M protein) in the blood or urine.  At that point, patients are generally classified into categories based on their clinical and laboratory evaluation.  Patients are also staged according to the severity of their disease based on a number of criteria.

A number of laboratory tests and medical procedures are used to help confirm a diagnosis of myeloma.  These tests should be conducted on all patients as part of an initial evaluation.

• A Complete Blood Count (CBC)
• A Chemistry profile checks levels of blood urea nitrogen (BUN) and blood levels of calcium, creatinine, and lactate dehydrogenase (LDH).  Increased BUN and creatinine indicate decreased kidney function, while LDH levels help assess tumor cell burden.
• Urinalysis measures levels of protein in the urine.
• Electrophoresis (EP) measures the levels of various proteins in the blood or urine.

• X-rays and other imaging tests can assess changes in the bone structure and determine the number and size of bone lesions.  These tests include:

  • A bone (skeletal) survey, which is a series of X-rays of the skull, spine, arms, ribs, and legs
  • Magnetic resonance imaging (MRI) provides detailed images of bone and soft tissue
  • Computerized axial tomography (CAT)
• Bone marrow aspiration or bone marrow biopsy can detect an increase in the number of plasma cells in the bone marrow.  An aspiration requires a sample of liquid bone marrow, and a biopsy requires a sample of solid bone tissue.  The procedure for doing these tests is similar except that a biopsy involves a larger needle.  In both tests, samples are taken from either the hip or breast bone and are examined under a microscope.  The percentage of plasma cells present is determined.  Multiple myeloma is probable if 10% or more of the cells in the bone marrow sample are plasma cells.

Patients may be classified into 1 of 4 myeloma categories to help to determine treatment options.

• Monoclonal Gammopathy of Undetermined Significance (MGUS)
• Smoldering Multiple Myeloma (SMM)
• Indolent Multiple Myeloma (IMM)
• Symptomatic Multiple Myeloma (MM)

Treatment and Prevention

While a myeloma diagnosis can be overwhelming, it is important to remember that there are several promising, new therapies that are helping patients live longer, healthier lives.

Patients in some myeloma categories do not have to receive treatment immediately.  In these cases, postponing therapy may help avoid unnecessary side-effects and the risk of complications associated with chemotherapy and delay development of resistance to chemotherapy.  Thus, knowing your classification is very important in deciding when it is appropriate to begin treatment.