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Multiple Myeloma

Multiple myeloma is a type of cancer formed by cancerous plasma cells in the blood. Normal plasma cells are an important part of the body’s immune system.

The immune system is made up of several types of cells that work together to fight infections. Lymph cells (called “lymphocytes”) are the main type of cell in the immune system. There are two types of lymph cells: T cells and B cells.

When B cells respond to an infection, they change into plasma cells. The plasma cells are mainly in the bone marrow—the soft, inner part of some bones. The plasma cells make proteins called antibodies that attack and help kill the germs.

When plasma cells grow out of control, they can form a tumor, usually in the bone marrow. This type of tumor is called a myeloma, and if there are many of them they are called multiple myeloma.

Having too many plasma cells can cause problems in the bone marrow where blood cells are made. This means that the bone marrow may not be able to make enough red blood cells, platelets, or normal white blood cells. This can cause problems such as the following:

Red blood cells: A shortage of red blood cells is called anemia. It can make you feel very tired.

Platelets: These cell fragments help stop bleeding after a wound. Without enough platelets you can bleed a lot after a minor cut or scrape.

White blood cells: A shortage of these cells is called leucopenia. Without enough normal white blood cells your body can’t resist infections.

Another problem is that the myeloma cells do not protect the body from infections. They make antibodies just as normal plasma cells do. But these antibodies do not work to kill germs.

There are two other forms of plasma cell disease: MGUS (monoclonal gammopathy of undetermined significance) and solitary plasmacytomas. These diseases are not cancer, but they sometimes change into cancer. People with these conditions need to be watched carefully.

Risk Factors:

These are the known risk factors for multiple myeloma:

Age and gender: Age is the biggest risk factor for multiple myeloma. Half of the people found to have this cancer are over 71 years old. Only 1% of cases are found in people younger than 40. Men are more likely to get this cancer than women.

Race: Multiple myeloma is about twice as common among African Americans as white Americans. The reason is not known.

Radiation exposure: Being exposed to radioactivity has been suggested as a risk factor. But this would account for only a very small number of cases.

Family history: This cancer seems to be more common in some families. But this is quite rare. Most patients have no other relatives with the disease.

Exposure on the job: Some studies suggest that workers in some oil-related industries may be at a higher risk.

Weight: A recent study found that being overweight increases a person’s risk of getting this cancer.

Other plasma cell diseases: Many people with other plasma cell diseases will develop multiple myeloma later.

While the exact cause of multiple myeloma is not known, scientists are learning how changes in DNA can cause plasma cells to become cancerous. DNA is the substance that tells our cells how to behave. Cancer can be caused by changes (mutations) in the DNA that controls cell growth.

Early Detection:

Symptoms

Some people don’t have any symptoms at all. The following are the most common symptoms of multiple myeloma:

Bone pain: There are cells in the bone marrow whose job it is to absorb old bone to make way for new bone. Plasma cell tumors can give off substances that "turn on" these cells. This can cause small areas of bone weakness. The weak areas are often painful. There can also be widespread bone weakness. These changes increase the risk of broken bones from minor stress or injury. Any bone can be involved, but pain in the backbone, hip bones, and skull is most common.

Blood problems: When myeloma replaces normal blood-forming marrow cells, the marrow often does not make enough red blood cells, white blood cells, and blood platelets. Symptoms include:

Nervous system symptoms: Bones in the spine may get weak and even collapse. They can press on certain nerves, causing severe pain, numbness, and/or muscle weakness. This is serious and you must contact your doctor as soon as possible if this happens.

If the blood absorbs too much calcium from damaged bone, weakness and confusion can result because calcium affects nerve cell function.

Sometimes, the abnormal proteins made by myeloma cells can damage nerves, causing weakness and numbness. In some patients, a lot of this protein can make the blood "thicken." This can slow blood flow to the brain and cause confusion, dizziness, and stroke-like symptoms. People with these symptoms should contact their doctor. Treatment is fairly simple: the doctor removes some of the protein out of the blood causing the problem. This treatment is called plasmapheresis.

Kidney symptoms: Too much myeloma protein or calcium in the blood can damage the kidneys. This makes it harder for the body to get rid of excess salt, fluid, and body waste products. People with this problem can feel weak and have swelling in the legs.

High blood calcium: When bone dissolves, it can release a lot of calcium into the blood. This can cause the kidneys to fail. One symptom is being very dry and thirsty. Others include loss of appetite, constipation, and feeling drowsy or sleepy.

Infections: Myeloma patients are about 15 times more likely to get infections. The most common and serious of these is pneumonia.

Laboratory Tests

The following are the laboratory tests done if symptoms suggest that a person might have multiple myeloma.

Blood and urine tests: The antibody made by cancerous plasma cells can collect at high levels in the blood. It may also be found in the urine. Finding abnormal antibodies in the blood and/or urine can help tell if there is a plasma cell tumor.

Bone marrow biopsy: This test is done to confirm that cancer is present. A doctor looks at some bone marrow tissue through a microscope to tell if there are cancer cells and, if so, how many.

For this test, the back of the pelvic bone is first numbed. Then a needle is used to remove some solid bone and some bone marrow, along with a few drops of fluid.

Bone x-rays: X-rays can show bone damage caused by myeloma cells

CT scan (computed tomography): A CT scan is a special type of x-ray that takes many pictures of the body. A computer combines the x-rays to make a detailed picture. CT scans can help to tell if your bones have been damaged by myeloma. They can also be used to guide a biopsy needle into a tumor. Often after the first set of pictures is taken, an injection of a dye will be given. This helps to better outline structures in the body. CT scans take longer than regular x-rays. The patient needs to lie still on a table for 15 to 30 minutes while they are being done.

MRI (magnetic resonance imaging): This test uses radio waves and strong magnets instead of x-rays. A computer translates the pattern of radio waves into cross-sectional pictures of the body. MRI scans are very helpful in looking at bones, but they take longer than CT scans.

Putting It All Together

No single test is enough to tell for sure if a person has multiple myeloma. Doctors look at all factors below:

Treatment:

Chemotherapy is use of drugs to kill or shrink the cancer cells. This treatment is useful for cancers such as multiple myeloma that often spread widely. Often several drugs are given together.

The choice and dose of drug therapy depend on many factors. These factors include:

If a stem cell transplant is planned, most doctors avoid using drugs that can damage the bone marrow.

Chemotherapy can have some side effects. These side effects will depend on the type of drugs given, the amount taken, and how long the treatment lasts. Side effects could include the following:

These side effects go away after treatment ends.

Thalidomide is a drug that was banned at one time because it caused birth defects. But it is now being used to treat myeloma. It is often combined with a steroid drug and can be very effective. It can be used before a blood-forming stem transplant. But it can cause major side effects such as severe constipation, numbness and tingling of the arms and legs, and tiredness. New drugs that are like thalidomide but which cause fewer side effects are starting to be used.

Another drug called bortezomib (Velcade) can be used for people whose disease has progressed after a least two earlier forms of treatment. Early studies showed that this drug could shrink tumors in about 3 out of 10 people who received it. Larger studies are being done to see if it helps patients live longer and whether it might be useful earlier in the course of the disease.

Side effects from bortezomib can include:

Relieving symptoms is an important goal of treatment. Many people with myeloma are most concerned about bone damage. The myeloma cells can actually cause bone to dissolve. This can lead to weakness and broken bones. Drugs called bisphosphonates can slow down this process. Many doctors recommend that treatment with a bisphosphonate begin along with chemotherapy.

Diuretics can help your kidneys remove excess body fluids and salts. And pain relievers can improve your quality of life. Studies show that cancer patients treated with pain relieving drugs live longer and are better able to go on with their normal activities.

Radiation Therapy

Radiation therapy is the use of high-energy x-rays to kill cancer cells. It is often used to treat areas of damaged bone that have not responded to chemotherapy and are causing pain.

Myeloma can weaken back bones so badly that the bones collapse and put pressure on the spinal cord and spinal nerves. This can cause sudden numbness or tingling, sudden weakness of leg muscles, or sudden problems with urinating or moving the bowels. This is a medical emergency that needs to be treated right away. The treatment may involve radiation therapy and/or surgery.

The type of radiation treatment used in treating multiple myeloma is called external beam therapy. This means the radiation is given from outside the body. Having this treatment is much like getting an x-ray. But the treatment lasts longer and is usually done several times weekly for several weeks.

Surgery

Surgery is very rarely used in treating multiple myeloma. As noted above, emergency surgery may be needed when the spinal cord is compressed. Surgery to attach metal rods or plates can help support weight-bearing bones in the spine or legs. This may be done to prevent bones from breaking.

Biologic Therapy

Biologic therapy (immunotherapy) is treatment that uses certain parts of the immune system to fight disease, even cancer. A person’s own immune system can be made to work harder, sometimes by using an outside source such as manmade proteins.

Interferon is a hormone-like substance released by some white blood cells and bone marrow cells. Interferon slows growth of myeloma cells. A man-made version of this substance is sometimes used together with chemotherapy. But interferon has mostly helped patients who have had chemotherapy and are in remission. Interferon seems to make remission last longer. Side effects of this drug include tiredness and flu-like symptoms. Some patients have trouble dealing with these symptoms. But overall the benefits of longer remission and fewer symptoms usually outweigh these side effects.

There is also a drug (erythropoietin) that can help correct low red blood cell counts (anemia). This drug can help with the symptoms of anemia such as weakness and tiredness.

High-Dose Chemotherapy and Blood-Forming Stem Cell Transplant (SCT)

This has become the standard treatment for younger myeloma patients in otherwise good health. It allows higher doses of chemotherapy to be used. Many centers are using this treatment for patients up to age 70. Several studies have shown that this treatment increases how long patients live compared to standard chemotherapy.

The first step in the process is to lower the amount of myeloma in a patient’s body. This is done with certain chemotherapy drugs. At the same time, blood-forming cells are taken from the patient's (or a donor's) blood or bone marrow. The cells (called stem cells) are then frozen. In some cases, bone marrow is used instead.

The patient then gets high-dose chemotherapy to kill the remaining myeloma cells. The treatment also destroys bone marrow stem cells. This would normally kill the patient. But the frozen stem cells can be given to the patient after chemotherapy. They are given into the bloodstream through an IV. The stem cells travel to the bone marrow where they begin to make new blood cells.

If the patient’s own stem cells are used, it is called an autologous transplant. These transplants are fairly safe and have a low risk of serious complications. Because of this, they can be used for older patients. But it is hard to kill all the myeloma cells with high-dose chemotherapy. Most patients who have autologous transplants will have their myeloma return at some point. Although a few of these patients will be free of myeloma for a long time, this procedure doesn’t cure the disease. Some doctors now recommend getting a second stem cell transplant (called a tandem transplant) within a year. While this may lengthen survival time, it can be hard on patients, and more research on this approach is needed.

When stem cells from a donor are used, the transplant is referred to as allogeneic. The donor is usually a close relative. Less often, it is an unrelated person whose tissue type closely matches that of the patient. Allogeneic transplants carry a higher risk of severe complications, even death. But they may produce longer remissions. This is because the donor’s immune system cells may actually help to destroy the myeloma cells. Allogeneic transplants are not used often in myeloma patients. There are two reasons for this: first, the patient must be fairly young and healthy to withstand the side effects of transplantation, and most myeloma patients are elderly. Second, a donor’s tissue type must match the patient's. Such matches can be hard to find.

Some allogeneic transplants use low doses of certain kinds of chemotherapy drugs to allow the transplanted stem cells to "take" without all the side effects of high doses. This is sometimes called a “mini-transplant” (nonmyeloablative transplant). This type of transplant allows the treatment to be done on older patients. Although the myeloma hasn’t been destroyed by the low-dose chemotherapy, the transplanted stem cells are expected to react against the myeloma cells and destroy them.

Plasmapheresis

In this treatment, a machine removes blood from a vein. The blood cells are then separated from the plasma (the liquid part of the blood) and returned into another vein. The abnormal antibodies released by the myeloma cells are in the plasma. The plasma is discarded and replaced with a salt solution and blood proteins from donors.

Plasmapheresis is helpful when build-up of myeloma proteins thickens the blood and hampers circulation. While this treatment can relieve some symptoms, it does not kill the myeloma cells.

Myeloma Survival Rates

Doctors use a special term to describe the percent of patients who survive and the length of time they survive. This term is the "5-year survival rate." It refers to the percent of patients who live at least 5 years after their cancer is found. Five-year relative survival rates leave out patients dying of other diseases. This means that anyone who died of another cause, such as heart disease, is not counted.

Of course, many people live much longer than 5 years. And improvements in treatment make the outlook even better for new patients.

The 5-year relative survival rate for multiple myeloma is around 32%. Survival is higher in younger people and lower in the elderly. Because these rates are based on people first treated more than 5 years ago, recent improvements in treatment often mean a better outlook for people today.

These numbers provide an overall picture, but keep in mind that every person’s situation is unique and statistics can’t predict exactly what will happen in your case. Talk with your cancer care team if you have questions about your personal chances of a cure, or how long you might survive your cancer. They know your situation best.

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