Multiple Myeloma is a cancer that arises from a proliferation of a particular type of white blood cells, namely, the plasma cell. Plasma cells are normal constituents of the bone marrow, and their expansion and the consequent overproduction of immunoglobulin lead to the characteristic symptoms of the disease: bone pain, fatigue, high calcium and renal failure.

For many years there was a very limited number of treatment options, but with improvements in both our understanding of the biology of the disease and the discovery of a number of new drugs, clinicians now have an expanding armamentarium at their disposal.

Frequently Asked Questions

1. What is an MGUS and does it need to be treated?

   An MGUS is a monoclonal gammopathy of uncertain significance and occurs when a patient has increased protein in their blood but none of the other signs of myeloma. While some of these patients will go on to develop myeloma, many won t; and thus therapy is not indicated, just close follow up.

2. Is myeloma inherited?

   Unlike certain other cancers, such as colon, breast and ovarian, there is little data to suggest that there is an inherited predisposition to developing myeloma.

3. If I have multiple myeloma, should I have an autologous bone marrow transplant?

   In the absence of significant other health problems, patients under 65 should certainly be referred to a transplant center for consideration for this procedure, as currently it produces the best 5-year survival.

Risk Factors
There are no classic risk factors for developing the disease, other than aging: the median age of most patients in many studies is in mid -60s, and virtually all patients are older than 40. There are no lifestyle habits that predispose to the development of myeloma, and screening has not been found to be helpful. Approximately 12,000 people a year are diagnosed with myeloma in the United States.

Symptoms
Most patients present to their doctor's office with complaints of bone pain or symptoms of anemia, such as shortness of breath or headache. With the increased use of automated testing of patients' blood, many patients are discovered to have an increased level of monoclonal proteins (immunoglobulins) long before they develop overt symptoms.

In fact, hematologist/oncologists are often asked to evaluate patients found to have such a "monoclonal spike" and distinguish between true myeloma and an entity called monoclonal gammopathy of uncertain significance (MGUS). The latter is usually only associated with an increase in serum or urinary proteins but not with bone lesions, kidney abnormalities or anemia. Approximately 5% of patients over the age of 70 are found to have a MGUS. Not all patients with MGUS go on to develop myeloma, and no treatment is initiated.

Myeloma is diagnosed with confirmation of a certain level of immunoglobulins either in the blood or urine and an increased percentage of plasma cells in the bone marrow. Skeletal X-rays are obtained looking for lytic bone lesions. Certain ancillary blood tests can help a doctor gauge the prognosis of a particular patient s myeloma, including tests that look at the chromosomal makeup of the plasma cells (cytogenetics). After the amount of protein is quantitated and the bone marrow biopsied, a skeletal survey (X-rays) and other blood tests are obtained and the clinicians are able to "stage" the patient. While staging a patient is not an exact science, it is useful in allowing the physician and patient to predict what the clinical course will likely be. Patients in the lower stage have a lower burden of disease and consequently tend to have a longer life expectancy.

Complications

Bone pain - 80% of patients present with bone pain, and 20-40% of patients develop high serum calcium during the course of their disease. Bone scans, a type of nuclear medicine test, is fairly insensitive at picking up areas of disease, and thus plain films or the emerging use of magnetic resonance imaging (MRI) is useful.

Renal failure - The causes of renal failure in this disease are many and include deposition of protein in the kidney, uric acid nephropathy, infection, and a unique sensitivity of the kidney to intravenous contrast dye. In general, patients presenting with renal failure have a worse prognosis.

Hyperviscosity - On occasion, the excess proteins secreted by the plasma cells cause a syndrome of neurologic and ocular complications, primarily from a mechanical sludging of proteins and a slowing down of blood flow. The problem, once recognized, is treated with a procedure called plasmaphresis, where a patient's blood is run over a column and the protein is removed (similar to dialysis). This provides only temporary relief - systemic therapy always follows, usually with chemotherapy.

Infections - Patients with myeloma, even before they are treated with immunosuppressive chemotherapy agents, are very susceptible to certain infections. Despite this, the use of prophylactic antibiotics has not yet been shown to be useful. The use of transfusions of immunoglobulins is controversial, but can be considered in certain situations when a patient has repeated infections.

Treatment Options
The standard therapy of multiple myeloma has not changed significantly in many years - a combination of an oral chemotherapy drug called melphelan and a corticosteroid called prednisone. Surgery, the backbone of therapy for many solid tumors, has virtually no role here, as plasma cells spread throughout the bone marrow and thus this is a systemic disease usually from diagnosis.

Occasionally plasma cells with remain localized in one area - there are called plasmacytomas and they are treated with radiation therapy.

Various groups have looked at more aggressive conventional chemotherapy but overall there has not been a significant improvement in survival. Patients treated with melphelan and prednisone have a response rate of approximately 60-70% and the median survival is two and a half years.

The most recent improvement in survival for younger patients with myeloma is autologous bone marrow transplantation (ABMT). In this procedure, a patient's stem cells (the cells that are responsible for dividing and repopulating the marrow after chemotherapy) are harvested and stored. This allows the patient to receive doses of chemotherapy significantly higher than could safely be given before. The patient s cells are then transfused back and they return to the marrow and repopulate it. The five-year survival after ABMT is significantly higher than when patients receive conventional chemotherapy (52% versus 12%), although the survival curves continue to dip. Nevertheless, despite the slightly greater risk and side-effects of a transplant, patients under 65 and perhaps even under 70 should be referred to a bone marrow center for transplant soon after their diagnosis. Younger patients can be considered for allogeneic transplantation, where someone else's marrow is given after intensive chemotherapy and radiation therapy. This technique of treating myeloma remains fairly new and in need of much further study.

Pamidronate - Also called Aredia, this drug is administered intravenously in the office and is not a traditional chemotherapy agents. It has been shown that when combined with chemotherapy, Aredia significantly delays the progression of new problems within the bones and thus can improve the patient's quality of life with minimal side-effects.

Radiation Therapy - External bean radiation therapy is very useful for controlling the painful symptoms associated with bony metastases. It cannot be delivered to all of the skeleton, however, which is why systemic therapy with chemotherapy is always initiated first, and radiation held for single sites that become problematic later.

Thalidomide - Perhaps the most interesting therapy on the horizon is Thalidomide, the notorious drug that caused such severe birth defects in the 1950s. It is hypothesized that Thalidomide acts as a anti-angiogenesis agent and prevents the growth of new blood vessels from the host to nurture the myeloma clones. Thalidomide can cause drowsiness and numbness in the fingers and toes, but it does not suppress the bone marrow as traditional chemotherapy does. In early trials, some patients whose disease progressed after bone marrow transplant responded to Thalidomide. Trials are underway to better understand how to incorporate this drug into the treatment of patients with myeloma.

Erythropoietin - Epo is a drug that stimulates the marrow to produce more red blood cells. Thus, while not fighting the underlying disease, it is extremely useful in improving the quality of life of myeloma patients, who can be anemic on the basis of their disease, the chemotherapy used to treat it, or renal failure. It is administered once a week by injection and has minimal side-effects.

Future Directions:

Understanding the underlying biology of the disease will allow investigators to establish novel therapies that target the cellular mechanisms or growth factors that promote plasma cell expansion. Clinical trials continue to search for new, effective drugs that can then be incorporated with current therapies. Hopefully the coming years will see continued advances against this serious hematological cancer.

Last Updated: January 31, 2001
Source: Eric Bernicker, M.D.
Texas Cancer Institute®

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