The Stages of Multiple Myeloma

Multiple myeloma – a deadly blood cancer – can be a devastating diagnosis. Learn what to expect in each stage of the disease...

Making a diagnosis of myeloma depends on finding abnormal plasma cells or their products somewhere in the body.

Plasma cells are cells of the immune system that make antibodies when they are functioning normally. In myeloma, these cells begin to grow and divide abnormally, and they make abnormal amounts of antibody-like proteins.

The growth of these plasma cells in the bone marrow can reduce the normal function of the bone marrow.

It can also result in thinned, weakened bones that are apt to break. Accumulation of the abnormal antibody-like protein in the blood can cause problems with blood flow to the kidney and other parts of the body.

Usually, symptoms related to these changes bring a patient to the doctor or raise the suspicion of myeloma.

Diagnosing Multiple Myeloma
The diagnosis and prognosis of multiple myeloma include the following:

Medical History
Diagnosis begins with a visit to the doctor. Sometimes, multiple myeloma is noted when blood tests are ordered for an unrelated reason. A biopsy will be necessary to confirm the presence of myeloma cells.

The doctor will ask about your symptoms and medical history. He or she will inquire about how your symptoms have progressed. The doctor may also ask about anything that may increase your risk of multiple myeloma, such as exposure to radiation or toxic chemicals.

Physical Exam
The doctor will perform a complete physical exam. This will focus on uncovering evidence of bone damage, anemia, or impaired circulation, each of which might be the result of myeloma.

Testing
To help with the diagnosis, your doctor may do any of the following:

X-rays – to check for any damage to bones

Urine tests – to check for high levels of antibody proteins
Blood tests – to check for problems associated with multiple myeloma:

Low levels of white or red blood cells

Increased levels of calcium, which can result from the destruction of bone by myeloma cells

High levels of antibody proteins and chemicals in the body related to decreased kidney function

Bone marrow aspiration or biopsy – A sample of liquid bone marrow is removed and tested for the presence of myeloma cells. This test can also indicate how well the bone marrow is functioning. The sample is obtained by inserting a needle into the pelvic bone, which may be done in the hospital or outpatient setting.

Cytology
Cytology is the study of cells. The cytology of cancer cells differs significantly from normal cells. Doctors use the unique cellular features seen on biopsy samples to determine the diagnosis and assess the prognosis of a cancer.

To diagnose myeloma, the doctor will look for abnormal plasma cells, which are the cells responsible for myeloma. A plasma cell labeling index, which measures the percentage of dividing plasma cells, is available in some labs. This test gives an idea of how fast the cancer cells are growing. A higher labeling index is associated with a worse prognosis because it means that there are more, faster reproducing plasma cells present than there should be.

Staging
Staging is the process by which doctors determine the prognosis of a cancer that has already been diagnosed. Staging is essential for making treatment decisions (for example, surgery vs. chemotherapy). Several features of the cancer are used to arrive at a staging classification, the most common being the size of the original tumor, extent of local invasion, and spread to distant sites (metastasis). Low staging classifications (0-1) imply a favorable prognosis, whereas high staging classifications (4-5) imply an unfavorable prognosis.
The Durie-Salmon staging system is used to stage multiple myeloma. The amount of tumor in the body is estimated based on the following factors:

Blood or urine level of abnormal antibody-like proteins: These are produced by myeloma cells.

Blood level of calcium: High levels are associated with bone damage caused by myeloma cells growing in the bone marrow and destroying the surrounding bone as their mass expands.

Bone damage evident on x-ray: This is also a result of destruction of bone caused by growing myeloma cells. This damage has a characteristic appearance on x-ray, and sometimes an x-ray alone will give good evidence of myeloma.

Blood hemoglobin level: Hemoglobin is the red pigment in red blood cells that carries oxygen to the cells. Low levels may indicate decreased production of red cells due to myeloma cells occupying the bone marrow.

Blood level of beta-2-microglobulin: This is another protein produced by myeloma cells. Increased levels of this protein suggest a large amount of myeloma in the body.
In general, the more myeloma cells and/or their products present in the body, the higher the stage and the worse the prognosis. Patients with higher stage disease also tend to have more symptoms from their disease. Based on the Durie-Salmon system, staging of multiple myeloma is as follows:

Stage I

A relatively small number of myeloma cells are present. (This can be measured by plasma cell index.)

Hemoglobin levels are slightly low.

Bone x-rays show no damage or only one area of damage.

Calcium levels are normal indicating that there is not much bone damage.

There is a small amount of abnormal antibody-like protein in the blood or urine.
Stage II

A moderate amount of myeloma cells are present.

Other factors fall in a range between Stage I and Stage III.
Stage III

A large amount of myeloma cells are present.

Hemoglobin levels are very low, indicating that the normal bone marrow cells are being crowded out.

Calcium levels are high, indicating that there is a large amount of bone destruction.

X-rays show more than three areas of bone destruction.

A large amount of abnormal antibody-like protein is in the blood or urine.

Prognosis
Prognosis is a forecast of the probable course and/or outcome of a disease or condition. Prognosis is most often expressed as the percentage of patients who are expected to survive over five or ten years.

Cancer prognosis is a notoriously inexact process. This is because the predictions are based on the experience of large groups of patients suffering from cancers at various stages. Using this information to predict the future of an individual patient is always imperfect and often flawed, but it is the only method available.

Prognoses provided in this monograph and elsewhere should always be interpreted with this limitation in mind. They may or may not reflect your unique situation.
The five-year survival rates for multiple myeloma based on stage are as follows:

Stage I: 50%

Stage II: 40%

Stage III: 10%-25%

Multiple Myeloma Treatment
While standard protocols have been established for the treatment of virtually all cancers, doctors will often modify them for their individual patients.

These modifications are based on many factors including the patient’s age, general health, desired results, and the specific characteristics of his cancer.

At present there is no cure for multiple myeloma. Treatment aims to keep symptoms under control for as long as possible. If you are not having symptoms, the doctor will probably recommend holding off with treatment. Studies show no increase in survival rates with early treatment.

Therapy typically begins when the disease progresses to the point that complications, such as fractures, are likely or you experience symptoms that decrease your ability to function or to enjoy life.

The main treatment option is chemotherapy. This is an appropriate treatment because multiple myeloma is a systemic disease, meaning that it affects the entire body. Chemotherapy is a systemic treatment.

Doctors often recommend bone marrow transplantation for patients younger than age 65 and who meet other criteria for this treatment. Although transplants seem to increase survival for some patients, these treatments do not cure myeloma, and they have had limited success.
Chemotherapy
Chemotherapy is the use of drugs to kill cancer cells. Unlike radiation and surgery, which are localized treatments, chemotherapy is a systemic treatment, meaning the drugs travel throughout the whole body. This means chemotherapy can reach cancer cells that may have spread, or metastasized, to other areas. Because myeloma is a systemic disease from the start, chemotherapy is the main treatment.

Currently, there is no cure for myeloma, so treatment is designed to prolong life by reducing the effects of myeloma on body functions and reducing discomfort. Chemotherapy is usually given after symptoms or complications develop because there has been no evidence that early treatment alters the course of the disease. Chemotherapy drugs are usually used in combination and given in cycles. The drugs can be given intravenously (IV) or by mouth. The IV drugs may be administered at the doctor’s office or in the hospital. Oral drugs may be taken at home. The type of chemotherapy often depends on the amount of tumor present in the body and how well the kidneys are functioning.

Chemotherapy is given until the abnormal antibody-like protein produced by myeloma cells decreases and reaches a plateau. Complete remission is rare.

Chemotherapy Drugs
Examples of chemotherapy drugs used for multiple myeloma include:

Bortezomib (Velcade)

Cyclophosphamide (Cytoxan)

Dexamethasone (Decadron)

Doxorubicin (Adriamycin)

Lenalidomide (Revlimid)

Melphalan (Alkeran)

Prednisone

Thalidomide (Thalomid)

Vincristine (Oncovin)

Combination therapy

Melphalan and prednisone

Vincristine, doxorubicin, and dexamethasone
Effectiveness
Fifty to 60% of patients reduce the amount of abnormal protein in their blood by half. But, fewer than 1 in 20 has a complete remission. Typically, multiple myeloma recurs within 1-2 years of ending chemotherapy. At this point, the doctor will usually recommend trying a different chemotherapy regimen. Typically, the combination therapy of melphalan and prednisone is given first. The combination therapy of vincristine, doxorubicin, and dexamethasone is given if the cancer returns.

Side Effects
Chemotherapy can affect your central nervous system. Because of this, you may feel tired, confused, and depressed. Usually, these feelings go away when the treatment ends. Other common side effects of chemotherapy include:

Flu-like symptoms

Fluid retention

Fatigue

Impaired memory

Inability to focus

Dizziness

Nausea or vomiting

Constipation

Diarrhea

Anemia

Muscle pain

Headache

Hair loss

Infertility

Rash
Possible Complications
Melphalan may increase your risk of developing leukemia or myelodysplasia (a disease that affects bone marrow). If you have been given melphalan, you will be closely monitored by your doctor for signs of these conditions.

Radiation Therapy
Radiation therapy is the use of penetrating beams of high-energy waves or streams of particles called radiation to treat disease. Radiation therapy destroys the ability of cancer cells to grow and divide.

There are a few cases in which radiation may be used to treat multiple myeloma:

If the tumor returns to one site and is causing symptoms

If a compression fracture in the spine is pressing against the spinal cord

If a bone marrow transplant is to be done, total body radiation may be given prior to this procedure to eliminate the myeloma cells and prepare the bone marrow for transplantation of the new, healthy stem cells.

Type of Radiation Therapy
External radiation is used to treat multiple myeloma. In external radiation therapy, rays are directed at the tumor from outside the body. Treatments are given at a hospital or radiation center once a day, five days per week. The daily time spent receiving external therapy is short.

Effectiveness
Radiation therapy does not cure multiple myeloma, but may be able to decrease symptoms.
Taking Care of Your Emotional Needs
Even though your needs are greater when you have cancer, it can be hard to ask for help to meet those needs. To get the help you need, think about turning to:

Family and friends

Others who also have cancer

People you meet in support groups

People from your spiritual or religious community

Health care providers

Caregivers

No one needs to face cancer alone. When people with cancer seek and receive help from others, they often find it easier to cope. You may find it hard to ask for or accept help. After all, you are used to taking care of yourself. Maybe you think that asking for help is a sign of weakness. Or perhaps you do not want to let others know that some things are hard for you to do. All these feelings are normal.

As one man with cancer said:

“I had always been the strong one. Now I had to turn to others for help. It wasn't easy at first, but the support of others helped me get through a lot of hard times.”

For more information, visit our Multiple Myeloma Health Center.

Please be aware that this information is provided to supplement the care provided by your physician. It is neither intended nor implied to be a substitute for professional medical advice. CALL YOUR HEALTHCARE PROVIDER IMMEDIATELY IF YOU THINK YOU MAY HAVE A MEDICAL EMERGENCY. Always seek the advice of your physician or other qualified health provider prior to starting any new treatment or with any questions you may have regarding a medical condition.

DISCLAIMER: This information is intended for educational purposes. EBSCO is in no way liable for the use of this information and makes no warranty or guarantee as to its accuracy.

Copyright © 2008 EBSCO Publishing

How Much Do You Know About Multiple Myeloma?
About 20,520 cases of multiple myeloma are diagnosed each year in the U.S., according to the American Cancer Society. Has your life been affected by a diagnosis?