Multiple Myeloma: Cancer Causes, Symptoms, Diagnosis, Treatment, Prevention

Multiple Myeloma: Cancer Causes, Symptoms, Diagnosis, Treatment, Prevention

What Is Multiple Myeloma?

In multiple myeloma, a certain kind of white blood cell called a plasma cell begins to multiply abnormally within the bone marrow. Normally, plasma cells are responsible for producing antibodies that help fight infections. In multiple myeloma, however, excessive plasma cells release unhealthy levels of protein (called immunoglobulin) into the bones and blood. The excessive protein accumulates throughout the body, causing organ damage. 

The plasma cells also cause problems inside bones, where they multiply and crowd out normal blood cells. Inside the bone marrow, multiple myeloma plasma cells release chemicals that prompt the body to dissolve areas of bone. This creates weak areas of bone, which are called lytic lesions.

As multiple myeloma progresses, plasma cells begin to spill out of the bone marrow and deposit elsewhere in the body, causing further organ damage.

Read more: Multiple Sclerosis Treatment, Causes, Types, Symptoms, Diagnosis And Prevention

Normal Cells

The body is made up of many kinds of cells. Each type of cell has special functions. Normal cells are produced in an orderly, controlled way as the body needs them. This process keeps us healthy.

Plasma cells and other white blood cells are part of the immune system, which helps protect the body from infection and disease. All white blood cells begin their development in the bone marrow, the soft, spongy tissue that fills the center of most bones. Certain white blood cells leave the bone marrow and mature in other parts of the body. Some of these develop into plasma cells when the immune system needs them to fight substances that cause infection and disease.

Plasma cells produce antibodies, proteins that move through the bloodstream to help the body get rid of harmful substances. Each type of plasma cell responds to only one specific substance by making a large amount of one kind of antibody. These antibodies find and act against that one substance. Because the body has many types of plasma cells, it can respond to many substances.

Myeloma Cells

When cancer involves plasma cells, the body keeps producing more and more of these cells. The unneeded plasma cells -- all abnormal and all exactly alike -- are called myeloma cells.

Myeloma cells tend to collect in the bone marrow and in the hard, outer part of bones. Sometimes they collect in only one bone and form a single mass, or tumor, called a plasmacytoma. In most cases, however, the myeloma cells collect in many bones, often forming many tumors and causing other problems. When this happens, the disease is called multiple myeloma. This booklet deals mainly with multiple myeloma.

(It is important to keep in mind that cancer is classified by the type of cell or the part of the body in which the disease begins. Although plasmacytoma and multiple myeloma affect the bones, they begin in cells of the immune system. These cancers are different from bone cancer, which actually begins in cells that form the hard, outer part of the bone. This fact is important because the diagnosis and treatment of plasmacytoma and multiple myeloma cancer are different from the diagnosis and treatment of bone cancer.)

Because people with multiple myeloma have an abnormally large number of identical plasma cells, they also have too much of one type of antibody. These myeloma cells and antibodies can cause a number of serious medical problems:

  • As myeloma cells increase in number, they damage and weaken bones, causing pain and sometimes fractures. Bone pain can make it difficult for patients to move.
  • When bones are damaged, calcium is released into the blood. This may lead to hypercalcemia -- too much calcium in the blood. Hypercalcemia can cause loss of appetite, nausea, thirst, fatigue, muscle weakness, restlessness, and confusion.
  • Myeloma cells prevent the bone marrow from forming normal plasma cells and other white blood cells that are important to the immune system. Patients may not be able to fight infection and disease.
  • The cancer cells also may prevent the growth of new red blood cells, causing anemia. Patients with anemia may feel unusually tired or weak.
  • Multiple myeloma patients may have serious problems with their kidneys. Excess antibody proteins and calcium can prevent the kidneys from filtering and cleaning the blood properly.

Causes of Multiple Myeloma

Multiple myeloma's cause is unknown. Certain risk factors slightly increase a person's chances of developing multiple myeloma. The risk factors are:

  • Being over age 65
  • Being male
  • Being African-American
  • Having a family member affected by multiple myeloma
A significant number of people with certain conditions will develop multiple myeloma. These conditions are:

  • Monoclonal gammopathy of uncertain significance (MGUS)
  • Solitary plasmacytoma
Rather than being causes of multiple myeloma, these conditions may be early forms of multiple myeloma.

What are risk factors for multiple myeloma?

The definitive cause of multiple myeloma has not been established but research has suggested several factors may be risk factors or contribute to multiple myeloma development in an individual. A genetic abnormality such as c-Myc oncogenes and others have been associated with multiple myeloma development. Currently, there is no evidence that heredity plays a role in multiple myeloma development. Environmental exposures to herbicides, insecticides, benzene, hair dyes, and radiation have been suggested as causes but definitive data is lacking. Inflammation and infection have been suggested but again not proven to cause multiple myeloma. However, a "benign" proliferation of a plasma cell can result in a situation where a monoclonal antibody is produced in high amounts (but not as high as seen with multiple myeloma). This result is termed monoclonal gammopathy of unknown or undetermined significance (abbreviated as MGUS). About 19% of MGUS patients develop multiple myeloma in about 2 to 19 years after MGUS diagnosis. In addition, about 7% of multiple myeloma patients develop MGUS within a year of developing multiple myeloma (this particular form of MGUS is termed secondary MGUS). Some researchers think MGUS antibody may result from as yet undetermined sources of inflammation or infection.

What are the signs and symptoms of multiple myeloma?

Multiple myeloma can have no symptoms, especially early in the disease, to severe symptoms, especially in those people diagnosed late in the disease process. The following is a list symptoms and signs of multiple myeloma that may be present in multiple myeloma:

  • Anemia
  • Bleeding
  • Nerve damage
  • Skin lesions
  • Enlarged tongue (macroglossia)
  • Bone tenderness or pain
  • Weakness or tiredness
  • Infections
  • Pathologic bone fractures
  • Spinal cord compression
  • Kidney failure

Multiple Myeloma Diagnosis

Most often, testing for multiple myeloma begins after a doctor discovers abnormal blood tests in someone with or without symptoms of multiple myeloma. Some common lab-test clues to the presence of multiple myeloma are:

  • High blood calcium (hypercalcemia)
  • Anemia (low red blood cell count)
  • Elevated creatinine (impaired kidney function)
  • High protein levels in blood, combined with a low albumin level (a "globulin gap")
  • Protein in the urine
When a doctor suspects multiple myeloma, tests of the blood, urine, and bones can make the diagnosis. The most important lab tests of the blood and urine are:

  • Serum protein electrophoresis (SPEP) and immunoelectrophoresis (IFE)
  • Urine protein electrophoresis (UPEP) and urinary immunoelectrophoresis (UFE)
Ninety-seven percent of people with multiple myeloma have an abnormal result on SPEP, UPEP, or both tests. 

An abnormal SPEP (IFE) and/or UPEP (UFE) may lead doctors to recommend a bone marrow biopsy. A bone marrow biopsy is a necessary step in the diagnosis of multiple myeloma. A needle is inserted into a bone, usually in the hip, and a sample of bone marrow is extracted. A diagnosis of multiple myeloma is made when the biopsy reveals an abnormally high number of plasma cells in the bone marrow.

Imaging tests also help doctors make a diagnosis of multiple myeloma and measure its spread. Plain X-ray films of the body's large bones (called a skeletal survey) can identify spots of bone weakened by multiple myeloma. In a few people, a CT scan, MRI, or PET scan may be needed to find bone involvement from multiple myeloma. 

What are the stages of multiple myeloma?

There are four stages of multiple myeloma. While many doctors use different staging, these are various stages cited by many clinicians:

  • Smoldering: Multiple myeloma with no symptoms
  • Stage I: Early disease with some symptoms
  • Stage II: Multiple symptoms and more advanced disease
  • Stage III: Multiple areas with multiple myeloma cells and more serious symptoms
Because staging criteria differ according to different groups, some clinicians simply define the individual's multiple myeloma without assigning a stage and simply estimate a prognosis (see below) for their patient. In 2013, an international group divided stages into three stages based on two criteria, the concentration of beta-2-microglobulin and serum albumen levels; over time this defined criteria may become widely accepted.

Multiple Myeloma Treatment

In general, multiple myeloma treatment primarily helps people who already have signs of organ damage from multiple myeloma. These signs include anemia, high blood calcium, impaired kidney function, or bone lytic lesions.

The initial therapy to treat multiple myeloma is known as induction therapy, using various drugs (described below). In persons under the age of 70, this may be followed by autologous stem cell transplantation (SCT), In SCT, some of a person's stem cells are removed by a machine and are frozen and stored. The stem cells are taken from the person with multiple myeloma, usually after induction therapy. The procedure continues this way:

  • The person with multiple myeloma undergoes high-dose chemotherapy. The strong chemotherapy destroys almost all the cells in the bone marrow -- both healthy cells and the plasma cells causing the disease.
  • The harvested stem cells are then injected into the person's veins. They travel to the bone marrow, where they multiply and make new healthy blood cells.
  • Some people undergo two stem cell transplantation procedures 6 months apart. This is known as tandem stem cell transplantation. Patterns of stem cell transplantation are undergoing clinical trial to determine which pattern is most effective.
  • Allogeneic transplantation is usually reserved for patients with multiple myeloma who have progressed after autologous stem cell transplantation. However, there are clinical trials utilizing tandem autologous stem cell followed by reduced intensity allogeneic stem cell transplantation.
  • After SCT, patients are usually take maintenance therapy for up to 2 years, usually with thalidomide or lenalidomide.
Stem cell transplantation doesn't cure multiple myeloma, but it leads to longer survival. However, SCT can cause serious complications, especially vulnerability to infections.

Chemotherapy refers to drugs that kill cancer cells. Chemotherapy alone is not as effective as stem cell transplantation for multiple myeloma treatment. However, chemotherapy is often a good option for people at higher risk for complications from stem cell transplantation.

To treat multiple myeloma, doctors generally use a combination of chemotherapy and other drugs, which may include:

  • Adriamycin (doxorubicin)
  • Alkeran (melphalan)
  • Cytoxan (cyclophosphamide)
  • Oncovin (vincristine)
  • Pomalyst (pomalidomide)
  • Revlimid (lenalidomide)
  • Thalomid (thalidomide)
  • Velcade (bortezomib)
Doctors can choose from multiple combinations of chemotherapy drugs. Corticosteroids (such as prednisone or dexamethasone) are often given with chemotherapy, to reduce side effects. Interferon is a hormone-like drug that can help keep multiple myeloma in remission after chemotherapy.

Bisphosphonates are drugs used to treat bone damage from multiple myeloma. With multiple myeloma, the bisphophonates primarily used are Aredia (pamidronate) and Zometa (zoledronic acid), which are given intravenously through a vein. A serious side effect of jaw bone death can occur with use of these medications, although it is rare.

Radiation therapy may also help treat multiple myeloma. A beam of radiation is directed from a machine to a bone or other part of the body affected by multiple myeloma. The high-energy rays kill multiple myeloma plasma cells, helping to reduce pain and stabilize the weakened bone. Multiple myeloma cells are highly sensitive to radiation. 

People who aren't candidates for SCT, usually due to age, are given induction therapy followed by chemotherapy.

Multiple myeloma research is ongoing, including clinical trials to identify more effective chemotherapy drugs and combinations.

The doctor also considers the person's age and general health. The doctor may want to discuss the patient's case with other doctors who treat multiple myeloma cancer. Also, the patient may want to talk with the doctor about taking part in a research study of new treatment methods. Such studies, called clinical trials, are designed to improve the treatment of this type of cancer. These studies are discussed in the Treatment Studies section.

Many patients want to learn all they can about their disease and their treatment choices so they can take an active part in decisions about their medical care. Patients have many important questions about their health, and the doctor is the best person to answer them. Most people want to know the extent of their cancer, how it can be treated, how effective the treatment is likely to be, and how much it is expected to cost. These are some questions patients may want to ask the doctor:

  • What are my treatment choices?
  • Would a clinical trial be appropriate for me?
  • What are the expected benefits of treatment?
  • What are the risks and possible side effects of treatment?
  • If I have pain, how will you help me?
  • Will I need to change my normal activities?
  • How often will I need to have checkups?

Many people find it helpful to make a list of their questions before they see the doctor. Taking notes can make it easier to remember what the doctor says. Some patients also find that it helps to have a family member or friend with them when they see the doctor -- to take part in the discussion or just to listen.

There is a lot to learn about cancer and its treatment. Patients do not need to ask all their questions or remember all the answers at one time. They will have other chances to ask the doctor to explain things and to get more information.

Multiple Myeloma Treatment Methods

Plasmacytoma and multiple myeloma are very hard to cure. Although patients who have a plasmacytoma may be free of symptoms for a long time after treatment, many eventually develop multiple myeloma. For those who have multiple myeloma, treatment can improve the quality of a patient's life by controlling the symptoms and complications of the disease.

People who have multiple myeloma but do not have symptoms of the disease usually do not receive treatment. For these patients, the risks and side effects of treatment are likely to outweigh the possible benefits. However, these patients are watched closely, and they begin treatment when symptoms appear. Patients who need treatment for multiple myeloma usually receive chemotherapy and sometimes radiation therapy.

Chemotherapy is the use of drugs to treat cancer. It is the main treatment for multiple myeloma. Doctors may prescribe two or more drugs that work together to kill myeloma cells. Many of these drugs are taken by mouth; others are injected into a blood vessel. Either way, the drugs travel through the bloodstream, reaching myeloma cells all over the body. For this reason, chemotherapy is called systemic therapy.

Anticancer drugs often are given in cycles -- a treatment period followed by a rest period, then another treatment and rest period, and so on. Most patients take their chemotherapy at home, as outpatients at the hospital, or at the doctor's office. However, depending on their health and the drugs being given, patients may need to stay in the hospital during treatment.

Radiation therapy (also called radiotherapy) uses high-energy rays to damage cancer cells and stop them from growing. In this form of treatment, a large machine aims the rays at a tumor and the area close to it. Treatment with radiation is local therapy; it affects only the cells in the treated area.

Radiation therapy is the main treatment for people who have a single plasmacytoma. They usually receive radiation therapy every weekday for 4 to 5 weeks in the outpatient department of a hospital or clinic.

People who have multiple myeloma sometimes receive radiation therapy in addition to chemotherapy. The purpose of the radiation therapy is to help control the growth of tumors in the bones and relieve the pain that these tumors cause. Treatment usually lasts for 1 to 2 weeks.

Treatment Studies Relevant to Multiple Myeloma

Because multiple myeloma is so hard to control, many researchers are looking for more effective treatments. They also are looking for treatments that have fewer side effects and for better ways to care for patients who have complications caused by this disease. When laboratory research shows that a new method has promise, doctors use it to treat cancer patients in clinical trials. These trials are designed to find out whether the new approach is both safe and effective and to answer scientific questions. Patients who take part in clinical trials may have the first chance to benefit from improved treatment methods, and they make an important contribution to medical science.

Many clinical trials of new treatments for multiple myeloma are under way. In some studies, doctors are testing new drugs and new drug combinations. In others, they are using chemotherapy along with biological therapy, treatment with substances that boost the immune system's response to cancer.

Researchers also are testing new approaches to cancer treatment that allow the use of very high doses of anticancer drugs, sometimes along with radiation. Doctors believe that higher doses of anticancer drugs and radiation might be more effective than the usual doses in destroying myeloma cells. However, higher doses also cause greater damage to healthy bone marrow. New approaches to treatment may help the healthy marrow recover or may allow doctors to replace marrow that is destroyed.

Patients interested in taking part in a clinical trial should discuss this option with their doctor.

One way to learn about clinical trials is through PDQ, a computerized resource developed by the National Cancer Institute. This resource contains information about cancer treatment and about clinical trials in progress all over the country. The Cancer Information Service can provide PDQ information to patients and the public.

Can multiple myeloma be prevented?

For some types of cancer, risk factors are known for the majority of cases. For example, smoking causes most lung cancers. This provides an opportunity for prevention. For other cancers, such as cervical cancer, pre-cancers can be detected early by a screening test (such as the Pap test) and treated before they develop into an invasive cancer.

With multiple myeloma, few cases are linked to risk factors that you can avoid. For those people with monoclonal gammopathy of undetermined significance or solitary plasmacytomas there is no known way to prevent multiple myeloma from developing.

Side Effects of Treatment of Multiple Myeloma

The methods used to treat multiple myeloma are very powerful. Treatment can help patients feel better by relieving symptoms such as bone pain. However, it is hard to limit the effects of therapy so that only cancer cells are destroyed. Because healthy cells also may be damaged, treatment can cause unpleasant side effects.

The side effects that patients have during cancer treatment vary for each person. They may even be different from one treatment to the next. Doctors try to plan treatment to keep side effects to a minimum. They also monitor patients very carefully so they can help with any problems that occur.

The side effects of chemotherapy depend on the drugs that are given. In general, anticancer drugs affect rapidly growing cells, such as blood cells that fight infection, cells that line the digestive tract, and cells in hair follicles. As a result, patients may have lower resistance to infection, loss of appetite, nausea, vomiting, or mouth sores. Patients also may have less energy and may lose their hair. One drug used to treat multiple myeloma, called prednisone, may cause swelling of the face and feet, burning indigestion, mood swings, restlessness, and acne. The side effects of chemotherapy usually go away over time after treatment stops.

During radiation therapy, the patient may be more tired than usual. Resting is important, but doctors usually advise patients to stay as active as they can. Also, the skin in the treated area may become red or dry. The skin should be exposed to the air but protected from the sun, and patients should avoid wearing clothes that rub the treated area. They should not use any lotion or cream on the skin without the doctor's advice. Patients may have other side effects, depending upon the areas treated. For example, radiation to the lower back may cause nausea, vomiting, or diarrhea because the lower digestive tract is exposed to radiation. The doctor often can prescribe medicine or suggest changes in diet to ease these problems. Side effects usually disappear gradually after radiation therapy is over.

Loss of appetite can be a problem for patients with multiple myeloma. People may not feel hungry when they are uncomfortable or tired. Some of the common side effects of cancer treatment, such as nausea and vomiting, can also make it hard to eat. Yet patients who eat well often feel better and have more energy, so good nutrition is important. Eating well means getting enough calories and protein to prevent weight loss, regain strength, and rebuild normal tissues. Many patients find that having several small meals and snacks during the day works better than having three regular meals.

Doctors, nurses, and dietitians can explain the side effects of cancer treatment and can suggest ways to deal with them.

Supportive Care

The complications of multiple myeloma can affect many parts of the body. Chemotherapy and radiation therapy often can help control complications such as pain, bone damage, and kidney problems. However, from time to time, most patients need additional treatment to manage these and other problems caused by the disease. This type of treatment, called supportive care, is given to improve patients' comfort and quality of life.

Patients with multiple myeloma frequently have pain caused by bone damage or by tumors pressing on nerves. Doctors often suggest that patients take pain medicine and/or wear a back or neck brace to help relieve their pain. Some patients find that techniques such as relaxation and imagery can reduce their pain.

Preventing or treating bone fractures is another important part of supportive care. Because exercise can reduce the loss of calcium from the bones, doctors and nurses encourage patients to be active, if possible. They may suggest appropriate forms of exercise. If a patient has a fracture or a breakdown of certain bones, especially those in the spine, a surgeon may need to operate to remove as much of the cancer as possible and to strengthen the bone.

Patients who have hypercalcemia may be given medicine to reduce the level of calcium in the blood. They also are encouraged to drink large amounts of fluids every day; some may need intravenous (IV) fluids. Getting plenty of fluids helps the kidneys get rid of excess calcium in the blood. It also helps prevent problems that occur when calcium collects in the kidneys.

If the kidneys aren't working well, dialysis or plasmapheresis may be necessary. In dialysis, the patient's blood passes through a machine that removes wastes, and the blood is then returned to the patient. Plasmapheresis is used to remove excess antibodies produced by the myeloma cells. This process thins the blood, making it easier for the kidneys and the heart to function.

Multiple myeloma weakens the immune system. Patients must be very careful to protect themselves from infection. It is important that they stay out of crowds and away from people with colds or other infectious diseases. Any sign of infection (fever, sore throat, cough) should be reported to the doctor right away. Patients who develop infections are treated with antibiotics or other drugs.

Patients who have anemia may have transfusions of red blood cells. Transfusions can help reduce the shortness of breath and fatigue that can be caused by anemia.

Living With Multiple Myeloma Cancer

The diagnosis of multiple myeloma can change the lives of patients and the people who care about them. These changes can be hard to handle. It is common for patients and their families and friends to have many different and sometimes confusing emotions.

At times, patients and their loved ones may feel frightened, angry, or depressed. These are normal reactions when people face a serious health problem. Most people handle their problems better if they can share their thoughts and feelings with those close to them. Sharing can help everyone feel more at ease and can open the way for people to show one another their concern and offer their support.

Worries about tests, treatments, hospital stays, and medical bills are common. Doctors, nurses, social workers, and other members of the health care team may help calm fears and ease confusion. They also can provide information and suggest resources.

Patients and their families are naturally concerned about what the future holds. Sometimes people use statistics to try to figure out whether a cure is possible or how long the patient will live. It is important to remember, however, that statistics are averages based on large numbers of patients. They can't be used to predict what will happen to a certain patient because no two cancer patients are alike. The doctor who takes care of the patient and knows his or her history is in the best position to discuss the person's outlook (prognosis).

People should feel free to ask the doctor about their prognosis, but not even the doctor knows for sure what will happen. Doctors may talk about the chances of remission. They also may talk about managing or controlling multiple myeloma cancer rather than curing it, even when patients respond well to treatment. They use these terms because the disease may get worse at a later time.

Services for Cancer Patients

Living with a serious disease isn't easy. Cancer patients and those who care about them face many problems and challenges. Finding the strength to cope with these difficulties is easier when people have helpful information and support services.

The doctor can explain the disease and give advice about treatment, working, or other activities. Patients also may want to discuss concerns about the future, family relationships, and finances. It may help to talk with a nurse, social worker, counselor, or member of the clergy.

Friends and relatives can be very supportive. Also, it helps many patients to meet and talk with others who are facing problems like theirs. Cancer patients often get together in support groups, where they can share what they have learned about cancer, its treatment, and coping with the disease. It's important to keep in mind, however, that each patient is different. Treatments and ways of dealing with cancer that work for one person may not be right for another -- even if they both have the same kind of cancer. It is always a good idea to discuss the advice of friends and family members with the doctor.

Often, a social worker at the hospital or clinic can suggest local and national groups that help with rehabilitation, emotional support, financial aid, transportation, or home care.