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Multiple myeloma is one of the several diseases that fall under the category of plasma cell dyscrasia. The disease results from an abnormality of the plasma cell. The plasma cell is part of the immune system that is responsible for forming antibodies against foreign organisms and substances that invade the body. The disease process occurs when one of these cells escapes from the control of the master immune system and behaves erratically by forming dysfunctional antibodies and dividing into numerous cells that the body does not need.


The exact cause of multiple myeloma and/or plasma cell dyscrasia is not clear. However, it appears that patients who have been involved in the agricultural, chemical, or radiology industries are at higher risk of developing the disease.


The incidence of multiple myeloma is increasing at an alarming rate in the United States with 13,000-15,000 new cases diagnosed each year. African-American men have the highest incidence rate and Caucasian women the lowest incidence rate.


There are no specific signs or symptoms of multiple myeloma. The following symptoms, if unexplained and unresolved for 8-12 weeks, may increase suspicion and prompt further testing.

  • Decreased energy level
  • Flu-like symptoms
  • Back pain (lower back pain more common)
  • Bone pain


The complex work up for myeloma is better understood when the mechanism of the damage caused by the myeloma cell is understood. This could be simplified by the following scenario:

When the myeloma plasma cell becomes independent of the immune system, it fails to sense that the protein it is forming is dysfunctional and uses the body's resources to manufacture large amounts of this protein. Myeloma cells reside in the bone marrow. The space used by these cells impairs the manufacturing of red blood cells, white blood cells, and platelets, resulting in low blood counts of red cells, white cells and platelets. As the myeloma cells continue to divide out of control, the space within the bone marrow narrows. The myeloma cells physically displace the bone structure, as well as secrete a chemical that destroys the bone. This bone destruction results in the bone pain, bone fractures, and increased calcium in the blood. In the meantime, the body tries to rid itself of the excess dysfunctional protein by excretion through the kidneys. This excess protein can directly damage the kidneys or the kidneys could be overwhelmed by the large amount protein. Either can result in kidney failure. In some cases, the abnormal protein deposits in different organs resulting in secondary amyloidosis.


There are no specific signs or symptoms of multiple myeloma. Decreased energy level, flu-like symptoms, back pain (especially low back pain), and bone pain, if unexplained and unresolved for 8-12 weeks, may increase suspicion and prompt further testing. In advanced disease, confusion, nausea, vomiting, and weakness may result from the high levels of calcium in the blood (hypercalcemia) or kidney failure. Pathologic fractures ( Fractures that occur without significan injury) could be the presenting symptom, as well. Easy bruisability secondary to low platelets or amyloidosis could be a presenting symptom in rare cases.


Physical Examination

In multiple myeloma, the physical examination is generally normal. Possible exceptions include "sausaging" of the blood vessels of the eyes and the ability to feel a plasmacytoma. (a collection of plasma cells under the skin that form a mass). Tenderness over affected bones, as well as hip ligaments, could be elicited. When plasmacytomas of the spine compromise the spinal cord, tenderness or pain may radiate around the chest or waist in a belt-like fashion. It can be elicited by pounding on the spine. If amyloid of the skin, and/or low platelet count, is a complication bruises could be noted.


  • Hematology The red blood cells, white blood cells, and platelets may be low depending on the amount of bone marrow involvement and the presence or absence of vitamin B12 or folate deficiency.
  • Blood Chemistry. The most common abnormality, and the one which dramatically increases the physician's level of suspicion of multiple myeloma, is an elevated protein, both in the blood and urine. In 25% of cases, the calcium may be elevated. High levels of uric acid, BUN/creatinine and/or coagulation dysfunction should be investigated. Serum vitamin B12 and red blood cell folic acid levels could be low in 10% of patients.
  • X-ray. A plain x-ray may show areas of bone damage.


The diagnosis is established by the demonstration of the abnormal protein in the serum and/or the urine, the presence of abnormal plasma cells (myeloma cells) in the bone marrow, low levels of normal antibodies, bone lesions, or plasmacytoma (a collection of plasma cells that forms a mass).

The work up of myeloma consists of:

  1. Protein electrophoresis and Myeloma Typing of serum and urine.
  2. Evaluation ofkidney function, serum calcium, uric acid levels, as well as other organ function.
  3. Evaluation ofthe amount of normal antibodies; the lower these levels, the more susceptible the patient is to infections.
  4. A complete bone survey ( x-rays) ofthe arms, legs, back, pelvis and skull to rule out any significant damage that needs immediate attention.
  5. A bone marrow biopsyto evaluate the number of myeloma cells, their activity in the bone marrow and, the extent of damage the myeloma cells have caused the normal bone marrow structure.


Monoclonal Gammopathy of Unknown Significance (MGUS)

This is the least aggressive subclass of plasma cell dyscrasia. Two percent (2%) of the American population 65 years or older do have MGUS. Patients have only a small abnormal protein spike (<3.0 gm/dl and <2.0 gm/dl for IgG and IgA and IgM, respectively), minimal or no bone marrow involvement (<10% plasma cells), no bony involvement, normal blood counts and usually normal levels of unaffected antibodies. The urine is usually free of monoclonal protein, however, it is not unusual to find small amounts of monoclonal light chains in the urine of MGUS patients. Patients with MGUS have a 20-25% chance of developing multiple myeloma or a related lymphoproliferative disorder. The remainder lead a normal life.

Smoldering Multiple Myeloma (SMM)

Patients with SMM have the same criteria as MGUS, except that the serum monoclonal protein level is >3.0 gm/dl, the percentage of plasma cells in the bone marrow is higher (10-20%), and a larger number of patients will have the levels of their normal antibodies suppressed. This group of patients does not have anemia, renal failure, or bone disease. About half of this patient population will progress to multiple myeloma and follow its course. The other, 50% will follow the course of MGUS.

Multiple Myeloma (MM)

The monoclonal protein level is >3.0 gm/dl or >2.0 gm for IgG or IgA and IgM, respectively. The bone marrow contains >20% plasma cells and all patients have abnormally low quantitative immunoglobulins. Depending on the stage of the disease, the timing of treatment is decided.


Plasmacytoma. is a collection of malignant "cancerous" plasma cells that form a mass. Plasmacytomas affect either bones or soft tissues where, depending on the site affected, the clinical cause is defined. Plasmacytoma could be part of multiple myeloma, if the criteria for the latter are satisfied or it could be a free standing true disease. Solitary plasmacytoma. of the soft tissue or the bone could be cured by local treatment (i.e. radiation therapy). Multiple plasmacytomas or plasmacytomas that are part of multiple myeloma are treated with systemic therapy.


The decision to treat patients with multiple myeloma depends if the patient has smoldering multiple myeloma, early indolent multiple myeloma, or active multiple myeloma. The treatment of multiple myeloma could be divided into three phases with the supportive component:

  • Induction Phase: The efforts and treatment are focused on reducing the amount of the disease.
  • Maintenance Phase: There is no current standard and no therapy is considered to be the accepted approach, however, biologic therapy, immune therapy or bone marrow transplantation could have a role.
  • Salvage Phase: is reserved for the treatment of patients in whom all know effective therapy with acceptable toxicity has failed.
  • Supportive Therapy: The use of growth factors, immunoglobulins, and antibiotics play a crucial role in the management of the disease.
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