What is multiple myeloma?

Multiple myeloma is a blood cancer (malignancy) of plasma cells where the body makes too many cancerous and more or less identical plasma cells.

Plasma cells are normally a very important part of the body’s immune system. Plasma cells are a specialized type of immune cell called a B-cell. They are programmed to help fight various infections primarily through producing an immunoglobulin. Immunoglobulins are made up of a heavy chain (called IgA, IgG, IgM, IgD or IgE) and a light chain (called kappa or lambda). Normally there is a nice mix of all of these to provide infection defense.

When plasma cells turn cancerous, they grow out of control in the bone marrow. Sometimes they form a discrete tumor (like a ball) called a plasmacytoma. Usually the tumors are spread throughout the bone marrow thus the term multiple myeloma. While about 90% of myelomas occur in multiple sites (multiple myeloma), it can sometimes occur in only one site (solitary myeloma or plasmacytoma), a few localized sites or involve other tissues like skin, muscle or lung (extramedullary myeloma). Almost 25,000 cases of multiple myeloma will be diagnosed in the United States this year.

The physicians at the Colorado Blood Cancer Institute (CBCI) are at the forefront of developing and testing new treatments for multiple myeloma. They specialize in the care of patients with multiple myeloma and other blood cancers and see only those kinds of patients.

What causes multiple myeloma?

The honest answer is that we do not know what causes myeloma. Some people are more prone to develop myeloma: older people, men more than women, and African-Americans more than Caucasians. Age is the most significant risk factor for multiple myeloma, since the average age at diagnosis is 68 years old. Men are more likely to contract the disease, and it is twice as common among African American men. Multiple myeloma seems to be common in some families, but this is rare.

Most if not all patients who develop myeloma have a pre-myeloma condition known as MGUS (monoclonal gammopathy of undetermined significance). MGUS is quite common, especially in older people where as many as 3-5% of people over 70-80 years have it. MGUS usually does not turn into myeloma. People with MGUS have roughly a 1% per year risk of developing myeloma. However, virtually all patients with myeloma had MGUS before, but most probably did not know it. There is no treatment for MGUS, however it should be monitored on a regular basis by a physician.

How is multiple myeloma diagnosed?

In the past, almost all patients diagnosed with myeloma had pain in the bones as the primary complaint. Now, with more widespread testing of the blood, many patients who are diagnosed who may not have bone pain or some of the other typical symptoms. Unfortunately many people who have multiple myeloma may not experience symptoms until the condition has reached an advanced stage. Some common symptoms include bone pain, anemia (fatigue), shortness of breath, dizziness, weakness, mental confusion, numbness, kidney failure and increased infections. Sometimes a fracture that seems to occur for no reason (pathologic fracture) is what brings a patient to medical attention and the diagnosis of myeloma.

No single test suffices to make a diagnosis of multiple myeloma, which is based on a combination of factors and tests, including the patient’s symptoms. Myeloma can behave very differently from one patient to another. Doctors use a variety of tests to detect and diagnose multiple myeloma, including:

  • Physical examination and history
  • Biopsy of bone, lymph nodes or tissue
  • Bone marrow aspiration and biopsy with special tests to check the chromosomes and DNA
  • Radiology studies (X-rays, MRI scan, CT scan, PET scan)
  • Complete blood count
  • Blood chemistry studies
  • Blood immunoglobulin studies (electrophoresis and immunofixation)
  • Urine test including electrophoresis and immunofixation
  • Serum free light chain test
  • Beta 2 microglobulin

Once multiple myeloma has been diagnosed, tests are completed to see how advanced the disease is (stage). The spread of most cancers is usually described as stages. For years the Durie-Salmon classification was used for staging; it has been being replaced by the International staging system. Stages are I, II or III. The purpose of staging is to provide prognostic information (how doctors think the myeloma might behave) and to guide treatment. These staging systems can be found on line at the International Myeloma Foundation website (http://myeloma.org/). The stage does not always tell the whole story: DNA or chromosome testing of the plasma cells can provide very important prognostic information as well and is usually considered by doctors in addition to the stage when thinking about how to treat a patient.

When myeloma is diagnosed, one needs to determine the following:

  • Is it “symptomatic”, that is, is the myeloma causing health issues in the patient? Some forms of myeloma are termed “smoldering” if they are not causing problems. These patients are the subjects of clinical trial testing (available at CBCI) to determine whether early treatment is a good idea.
  • What type of immunoglobulin is made by the myeloma? What heavy chain? What light chain? This is important in following the myeloma on treatment.
  • What is the stage?
  • Is the myeloma a more typical kind (standard risk), or a more aggressive kind (high risk)?

What are the treatment options?

Many different types of treatment are available for patients with multiple myeloma. The treatments are changing nearly every year with advances in knowledge from clinical research. Unfortunately, multiple myeloma is still felt with rare exception to be an incurable cancer. However, in most cases it is highly treatable. Twenty to thirty years ago half of all people diagnosed with myeloma were dead by 30 months. Now, most patients (with the possible exception of those patients diagnosed with particularly nasty and aggressive forms of myeloma) are living much longer, often more than 8-10 years. Clinical trials are underway to improve current treatments and develop new treatments. The prognosis (chances of recovery) and treatment options depend on the age of the patient, the stage of the disease, the chromosome changes, and the patient’s general health and symptoms.

The myeloma program at CBCI has been directly involved in the development and approval of virtually all the most important myeloma treatment through the conduct of clinical trials. …

Standard treatments for multiple myeloma:

  • We do not treat MGUS
  • Smoldering or asymptomatic myeloma is only treated on clinical trials since we do not know if treatment really is necessary.
  • We treat ALL patients with symptomatic myeloma with chemotherapy
  • Seven new drugs (thalidomide, bortezomib, lenalidomide, liposomal doxorubicin, pomalidomide, carfilzomib, panobinostatxxx) have been FDA approved since 2000 and form the backbone of treatment, often combined with some of the older medications
  • There are many different types and combinations of chemotherapy and treatment is usually tailored to the patient
  • Younger, more vigorous patients are often treated differently than older or more frail patients
  • Bone strengthening medicines are very often used (pamidronate, zoledronic acid)
  • High-dose chemotherapy with autologous stem cell transplantation is used in more vigorous patients, often after the first several months of standard chemotherapy, and remain a standard treatment
  • Allogeneic transplants (using donor cells, more aggressive and potentially dangerous, but can be highly effective is sometimes offered to younger patients)
  • Radiation therapy to bone lesions
  • Kyphoplasty for compression fractures of the spine
  • Plasmapheresis for a few patients with severe kidney problems

Clinical trials testing new treatments and new chemotherapy drugs are very important. Discuss this with your physician at the CBCI.