New Options to Treat Multiple Myeloma

Multiple myeloma is cancer of the bone marrow, an incurable type of the disease that kills about 10,700 people a year. But for the 22,000 diagnosed annually, including recently Tom Brokaw, former NBC news anchor, there are new options for treatment and more kinds of therapies in the works, according to Dr. Gary I. Cohen, medical director of the Sandra & Malcolm Berman Cancer Institute at Greater Baltimore Medical Center. He answers questions about the disease.

What is multiple myeloma?

Multiple myeloma is a cancer of plasma cells, a type of immune cell normally responsible for producing disease-fighting antibodies. Primarily occupying bone marrow, plasma cells help protect the body from harmful substances.

Occasionally, one of these cells becomes malignant and grows without the usual checks and balances of other cellular elements within the body. The term multiple myeloma means that multiple bones are affected by the malignant “myeloma” cell. On rare occasions, this same cell can form a tumor in a single bone or other tissue.

What causes it?

Myeloma is caused by a genetic defect in the plasma cell which alters its growth pattern. This disease is seen increasingly with age, making it more common in older people, with occasional occurrences in younger individuals. Changes in DNA might allow the cells to become cancerous, eventually affecting other areas of the body including the bones, kidneys and overall immune system. However, it is not considered a genetic form of malignancy which might be passed to children. Nevertheless, rare families have been observed to have an increased risk of developing myeloma and related disorders.

What are the symptoms?

Symptoms result from bone marrow being overrun with abnormal plasma cells, causing bone pain, anemia, fatigue, tiredness or shortness of breath. If blood cells are severely affected, patients may experience unusual bleeding or frequent infections. Very late in the disease, complications may arise from the accumulation of myeloma cells and the secretion of excessive antibodies. The bones may weaken, resulting in risk of fracture and possible liberation of excessive calcium into the bloodstream causing confusion, dehydration and other symptoms. The antibody protein increases in the blood, causing thickening of the blood and possible kidney damage. The resulting kidney failure may cause weakness and swelling and could ultimately result in death.

How is it diagnosed?

Because the antibodies produced by the plasma cells can be easily detected and measured in the bloodstream, myeloma is often diagnosed at a very early stage. However, detection of this protein could also be a benign finding, making it difficult to predict the subsequent clinical course of newly diagnosed patients. Therefore, patients with a myeloma protein are often referred to a hematologist to further evaluate whether the abnormal finding is significant or not. Ultimately, a sample of the bone marrow is required to determine the amount of plasma cells within the marrow itself, which confirms the diagnosis. When myeloma is first diagnosed, it almost always has already spread extensively within the bone marrow itself, so it is rarely limited to one specific bone.

What is meant by “incurable, but treatable?”

Whenever cancer is diagnosed, everyone likes to think about overall prognosis. Cancer staging systems have been carefully devised and tested to predict survival. Several systems exist for multiple myeloma, but the course of treatment is quite variable. Some exhibit a “smoldering” form of the disease, so even though the diagnosis is confirmed, patients may remain in a stable, untreated phase for months or years. Others may have a very slow progression over time. While average survival is measured in years (more than five years for early-stage disease) the assessment of survival is a moving target due to recent new therapies. Our treatment opportunities, fairly effective at keeping patients alive longer, are changing so rapidly that survival for a patient diagnosed in 2014 is likely far better than any report based on studies currently published.

How is it treated?

The treatment of myeloma remained basically unchanged for about 40 years, but has advanced substantially over the past decade. Traditional chemotherapy approaches have included steroids, and other cytotoxic agents that have substantially improved the overall survival and reduced complications from progressive myeloma but often with the risk of toxicity. A major advance in treatment of myeloma occurred with the “rediscovery” of thalidomide, an old drug which became famous for causing birth defects in pregnant women. However, thalidomide and related compounds (lenalidomide, pomalidomide) have resulted in dramatic improvements in the treatment and prognosis of myeloma. New classes of drugs, called proteasome inhibitors, have added further benefits in treating myeloma. Additional agents which specifically target unique mechanisms of the malignant process in myeloma are in late stages of development and should be available in the near future. These exciting new agents are currently available in clinical trials at GBMC and elsewhere and hopefully will again favorably affect the treatment and prognosis of this disease. Because of these remarkable advances in therapeutics, myeloma experts at major academic institutions have begun to question whether bone marrow (or stem cell) transplants will play any role in the treatment of myeloma in the future. As clinicians, we look forward with great optimism to a time when treatment of multiple myeloma may be increasingly targeted, far more effective, and more tolerable than it is today.

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