Multiple myeloma

Synonyms

5

Overview

Multiple myeloma is a cancer of plasma cells, a type of white blood cell normally responsible for producing antibodies. In multiple myeloma, collections of abnormal plasma cells accumulate in the bone marrow, where they interfere with the production of normal blood cells. Most cases of multiple myeloma also feature the production of a paraprotein—an abnormal antibody which can cause kidney problems. Bone lesions and hypercalcemia (high blood calcium levels) are also often encountered.

Multiple myeloma is diagnosed with blood tests (serum protein electrophoresis, serum free kappa/lambda light chain assay), bone marrow examination, urine protein electrophoresis, and X-rays of commonly involved bones.

Multiple myeloma is considered to be incurable but treatable. Remissions may be induced with steroids, chemotherapy, proteasome inhibitors, immunomodulatory drugs such as thalidomide or lenalidomide, and stem cell transplants. Radiation therapy is sometimes used to reduce pain from bone lesions.

Symptoms

In some cases, multiple myeloma is not associated with any signs and symptoms. When present, the most common symptom is anaemia (low red blood cell count), which can be associated with fatigue, shortness of breath, and dizziness. Other features of the condition may include:

  • Bone pain
  • Nausea
  • Constipation
  • Loss of appetite
  • Frequent infections
  • Weight loss
  • Excessive thirst
  • Weakness and/or numbness in the arms and legs
  • Confusion
  • Abnormal bleeding
  • Weak bones that may break easily
  • Difficulty breathing

When the disease is well-controlled, there may be neurological symptoms resulting from current treatments, some of which may cause peripheral neuropathy, manifesting itself as numbness or pain in the hands, feet, and lower legs.

Causes

Although the exact underlying cause of multiple myeloma is poorly understood, the specific symptoms of the condition result from abnormal and excessive growth of plasma cells in the bone marrow. Plasma cells help the body fight infection by producing proteins called antibodies. In people with multiple myeloma, excess plasma cells form tumors in the bone, causing bones to become weak and easily broken. The abnormal growth of plasma cells also makes it more difficult for the bone marrow to make healthy blood cells and platelets. The plasma cells produced in multiple myeloma produce abnormal antibodies that the immune system is unable to use. These abnormal antibodies build up in the body and cause a variety of problems.

Factors that are associated with an increased risk of developing multiple myeloma include increasing age, male sex, African American race, radiation exposure, a family history of the condition, obesity, and/or a personal history of monoclonal gammopathy of undetermined significance (MGUS).

Prevention

When it comes to multiple myeloma prevention, there are several challenges. The fact is, that there are no known multiple myeloma causes. Furthermore, the known risk factors, such as those involving age and race, cannot be avoided. Scientists are looking at whether other factors, such as obesity or pesticides, play a role in multiple myeloma; however, at this point, they are not considered risk factors for multiple myeloma. Finally, multiple myeloma research scientists do not know of any protective factors for this type of cancer. Therefore, it is not known how (or even if) multiple myeloma can be prevented.

Diagnosis

In some cases, your doctor may detect multiple myeloma accidentally when you undergo a blood test for some other condition. In other cases, your doctor may suspect multiple myeloma based on your signs and symptoms.

Tests and procedures used to diagnose multiple myeloma include:

  • Blood tests. Laboratory analysis of your blood may reveal the M proteins produced by myeloma cells. Another abnormal protein produced by myeloma cells — called beta-2-microglobulin — may be detected in your blood and give your doctor clues about the aggressiveness of your myeloma. Additionally, blood tests to examine your kidney function, blood cell counts, calcium levels and uric acid levels can give your doctor clues about your diagnosis.

  • Urine tests. Analysis of your urine may show M proteins, which are referred to as Bence Jones proteins when they're detected in urine.

  • Examination of your bone marrow. Your doctor may remove a sample of bone marrow for laboratory testing. The sample is collected with a long needle inserted into a bone (bone marrow aspiration and biopsy).

    In the lab, the sample is examined for myeloma cells. Specialized tests, such as fluorescence in situ hybridization (FISH) can analyze myeloma cells to understand their chromosome abnormalities. Tests are also done to measure the rate at which the myeloma cells are dividing.

  • Imaging tests. Imaging tests may be recommended to detect bone problems associated with multiple myeloma. Tests may include X-ray, MRI, CT or positron emission tomography (PET).

Assigning a stage and a risk category:
If tests indicate you have multiple myeloma, your doctor will use the information gathered from the diagnostic tests to classify your disease as stage 1, stage 2 or stage 3. Stage 1 indicates a less-aggressive disease and stage 3 indicates an aggressive disease that may affect bone, kidneys and other organs.

Prognosis

The long-term outlook (prognosis) for people with multiple myeloma can be difficult to predict as some cases progress rapidly despite treatment, while others remain stable without therapy for a number of years. However, some general patterns have been observed. For example, prognosis appears to vary based on the affected person's age and the stage of the condition at the time of diagnosis. In general, survival is higher in younger people and lower in the elderly. Other factors that can be associated with a poor prognosis include a high tumor burden and kidney damage.

Infections are an important cause of early death among people with multiple myeloma. In fact, studies show that the risk of both bacterial infections and viral infections is approximately seven times higher in people affected by the condition.

Genetic testing:
The stage and risk category will help your doctor understand your prognosis and your treatment options. Some myeloma centers now employ genetic testing, which they call a “gene array.” By examining DNA, oncologists can determine if patients are high risk or low risk of the cancer returning quickly following treatment.

Cytogenetic analysis of myeloma cells may be of prognostic value, with deletion of chromosome 13, non-hyperdiploidy and the balanced translocations t(4;14) and t(14;16) conferring a poorer prognosis. The 11q13 and 6p21 cytogenetic abnormalities are associated with a better prognosis.

Prognostic markers such as these are always generated by retrospective analyses, and it is likely that new treatment developments will improve the outlook for those with traditionally "poor-risk" disease.

Treatment

Though there's no cure for multiple myeloma, with good treatment results you can usually return to near-normal activity.

Standard treatment options include:

  • Targeted therapy. Targeted drug treatment focuses on specific abnormalities within cancer cells that allow them to survive. Bortezomib (Velcade) and carfilzomib (Kyprolis) are targeted drugs that block the action of a substance in myeloma cells that breaks down proteins. This action causes myeloma cells to die. Both medications are administered through a vein in your arm.
  • Biological therapy. Biological therapy drugs use your body's immune system to fight myeloma cells. The drugs thalidomide (Thalomid), lenalidomide (Revlimid) and pomalidomide (Pomalyst) enhance the immune system cells that identify and attack cancer cells. These medications are taken in pill form.
    Daratumumab (Darzalex) is approved by the FDA  in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy.
  • Chemotherapy. Chemotherapy drugs kill fast-growing cells, including myeloma cells. Chemotherapy drugs can be given through a vein in your arm or taken in pill form. High doses of chemotherapy drugs are used before a stem cell transplant.
  • Corticosteroids. Corticosteroids, such as prednisone and dexamethasone, regulate the immune system to control inflammation in the body. They also are active against myeloma cells. Corticosteroids can be taken in pill form or administered through a vein in your arm.

  • Stem cell transplantation. A stem cell transplant is a procedure to replace your diseased bone marrow with healthy bone marrow.

    Before a stem cell transplant, blood-forming stem cells are collected from your blood. You then receive high doses of chemotherapy to destroy your diseased bone marrow. Then your stem cells are infused into your body, where they travel to your bones and begin rebuilding your bone marrow.

  • Radiation therapy. This treatment uses beams of energy, such as X-rays, to damage myeloma cells and stop their growth. Radiation therapy may be used to quickly shrink myeloma cells in a specific area — for instance, when a collection of abnormal plasma cells form a tumor (plasmacytoma) that's causing pain or destroying a bone.

Because multiple myeloma can cause a number of complications, you may also need treatment for those specific conditions:

  • Bone pain. Pain medications, radiation therapy and surgery may help control bone pain.
  • Kidney complications. People with severe kidney damage may need dialysis.
  • Infections. Your doctor may recommend certain vaccines to prevent infections, such as the flu and pneumonia.
  • Bone loss. Your doctor may recommend medications called bisphosphonates, such as pamidronate (Aredia) or zoledronic acid (Zometa), to help prevent bone loss.
  • Anemia. If you have persistent anemia, your doctor may recommend medications to increase your red blood cell count.

Resources

Refer to Research Publications.