Multiple Myeloma Treatment- Cancer/Oncology, Neurology

Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment (PDQ®) – Patient Version was originally published by the National Cancer Institute.

KEY POINTS

• Plasma cell neoplasms are diseases in which the body makes too many plasma cells.

• Plasma cell neoplasms can be benign (not cancer) or malignant (cancer).

• There are several types of plasma cell neoplasms.

  • Monoclonal gammopathy of undetermined significance (MGUS)

  • Plasmacytoma

  • Multiple myeloma

• Multiple myeloma and other plasma cell neoplasms may cause a condition called amyloidosis.

• Age can affect the risk of plasma cell neoplasms.

• Tests that examine the blood, bone marrow, and urine are used to detect (find) and diagnose multiple myeloma and other plasma cell neoplasms.

• Certain factors affect prognosis (chance of recovery) and treatment options.

Plasma cell neoplasms are diseases in which the body makes too many plasma cells.

Plasma cells develop from B lymphocytes (B cells), a type of white blood cell that is made in the bone marrow. Normally, when bacteria or viruses enter the body, some of the B cells will change into plasma cells. The plasma cells make antibodies to fight bacteria and viruses, to stop infection and disease.

Plasma cell neoplasms are diseases in which abnormal plasma cells or myeloma cells form tumors in the bones or soft tissues of the body. The plasma cells also make an antibody protein, called M protein, that is not needed by the body and does not help fight infection. These antibody proteins build up in the bone marrow and can cause the blood to thicken or can damage the kidneys.

Plasma cell neoplasms can be benign (not cancer) or malignant (cancer).

Monoclonal gammopathy of undetermined significance (MGUS) is not cancer but can become cancer. The following types of plasma cell neoplasms are cancer:

• Lymphoplasmacytic lymphoma. (See Adult Non-Hodgkin Lymphoma Treatment for more information.)

• Plasmacytoma.

• Multiple myeloma.

There are several types of plasma cell neoplasms.

Plasma cell neoplasms include the following:

Monoclonal gammopathy of undetermined significance (MGUS)

In this type of plasma cell neoplasm, less than 10% of the bone marrow is made up of abnormal plasma cellsand there is no cancer. The abnormal plasma cells make M protein, which is sometimes found during a routine blood or urine test. In most patients, the amount of M protein stays the same and there are no signs, symptoms, or health problems.

In some patients, MGUS may later become a more serious condition, such as amyloidosis, or cause problems with the kidneys, heart, or nerves. MGUS can also become cancer, such as multiple myeloma, lymphoplasmacytic lymphoma, or chronic lymphocytic leukemia.

Plasmacytoma

In this type of plasma cell neoplasm, the abnormal plasma cells (myeloma cells) are in one place and form one tumor, called a plasmacytoma. Sometimes plasmacytoma can be cured. There are two types of plasmacytoma.

• In isolated plasmacytoma of bone, one plasma cell tumor is found in the bone, less than 10% of the bone marrow is made up of plasma cells, and there are no other signs of cancer. Plasmacytoma of the bone often becomes multiple myeloma.

• In extramedullary plasmacytoma, one plasma cell tumor is found in soft tissue but not in the bone or the bone marrow. Extramedullary plasmacytomas commonly form in tissues of the throat, tonsil, and paranasal sinuses.

Signs and symptoms depend on where the tumor is.

• In bone, the plasmacytoma may cause pain or broken bones.

• In soft tissue, the tumor may press on nearby areas and cause pain or other problems. For example, a plasmacytoma in the throat can make it hard to swallow.

Multiple myeloma

In multiple myeloma, abnormal plasma cells (myeloma cells) build up in the bone marrow and form tumors in many bones of the body. These tumors may keep the bone marrow from making enough healthy blood cells. Normally, the bone marrow makes stem cells (immature cells) that become three types of mature blood cells:

• Red blood cells that carry oxygen and other substances to all tissues of the body.

• White blood cells that fight infection and disease.

• Platelets that form blood clots to help prevent bleeding.

As the number of myeloma cells increases, fewer red blood cells, white blood cells, and platelets are made. The myeloma cells also damage and weaken the bone.

Sometimes multiple myeloma does not cause any signs or symptoms. This is called smoldering multiple myeloma. It may be found when a blood or urine test is done for another condition. Signs and symptoms may be caused by multiple myeloma or other conditions. Check with your doctor if you have any of the following:

• Bone pain, especially in the back or ribs.

• Bones that break easily.

• Fever for no known reason or frequent infections.

• Easy bruising or bleeding.

• Trouble breathing.

• Weakness of the arms or legs.

• Feeling very tired.

A tumor can damage the bone and cause hypercalcemia (too much calcium in the blood). This can affect many organs in the body, including the kidneys, nerves, heart, muscles, and digestive tract, and cause serious health problems.

Hypercalcemia may cause the following signs and symptoms:

• Loss of appetite.

• Nausea or vomiting.

• Feeling thirsty.

• Frequent urination.

• Constipation.

• Feeling very tired.

• Muscle weakness.

• Restlessness.

• Confusion or trouble thinking.

Multiple myeloma and other plasma cell neoplasms may cause a condition called amyloidosis.

In rare cases, multiple myeloma can cause peripheral nerves (nerves that are not in the brain or spinal cord) and organs to fail. This may be caused by a condition called amyloidosis. Antibody proteins build up and stick together in peripheral nerves and organs, such as the kidney and heart. This can cause the nerves and organs to become stiff and unable to work the way they should.

Amyloidosis may cause the following signs and symptoms:

• Feeling very tired.

• Purple spots on the skin.

• Enlarged tongue.

• Diarrhea.

• Swelling caused by fluid in your body's tissues.

• Tingling or numbness in your legs and feet.

Age can affect the risk of plasma cell neoplasms.

Anything that increases your risk of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn't mean that you will not get cancer. Talk with your doctor if you think you may be at risk.

Plasma cell neoplasms are most common in people who are middle aged or older. For multiple myeloma and plasmacytoma, other risk factors include the following:

• Being black.

• Being male.

• Having a personal history of MGUS or plasmacytoma.

• Being exposed to radiation or certain chemicals.

Tests that examine the blood, bone marrow, and urine are used to detect (find) and diagnose multiple myeloma and other plasma cell neoplasms.

The following tests and procedures may be used:

• Physical exam and history : An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken.

• Blood and urine immunoglobulin studies: A procedure in which a blood or urine sample is checked to measure the amounts of certain antibodies (immunoglobulins). For multiple myeloma, beta-2-microglobulin, M protein, free light chains, and other proteins made by the myeloma cells are measured. A higher-than-normal amount of these substances can be a sign of disease.

• Bone marrow aspiration and biopsy : The removal of bone marrow, blood, and a small piece of bone by inserting a hollow needle into the hipbone or breastbone. A pathologist views the bone marrow, blood, and bone under a microscope to look for abnormal cells.

• The following test may be done on the sample of tissue removed during the bone marrow aspiration and biopsy:

  • Cytogenetic analysis : A test in which cells in a sample of bone marrow are viewed under a microscope to look for certain changes in the chromosomes. Other tests, such as fluorescence in situ hybridization (FISH) and flow cytometry, may also be done to look for certain changes in the chromosomes.

• Skeletal bone survey: In a skeletal bone survey, x-rays of all the bones in the body are taken. The x-rays are used to find areas where the bone is damaged. An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body.

• Complete blood count (CBC) with differential : A procedure in which a sample of blood is drawn and checked for the following:

  • The number of red blood cells and platelets.

  • The number and type of white blood cells.

  • The amount of hemoglobin (the protein that carries oxygen) in the red blood cells.

  • The portion of the blood sample made up of red blood cells.

• Blood chemistry studies : A procedure in which a blood sample is checked to measure the amounts of certain substances, such as calcium or albumin, released into the blood by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease.

• Twenty-four-hour urine test: A test in which urine is collected for 24 hours to measure the amounts of certain substances. An unusual (higher or lower than normal) amount of a substance can be a sign of disease in the organ or tissue that makes it. A higher than normal amount of protein may be a sign of multiple myeloma.

• MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. This procedure is also called nuclear magnetic resonance imaging (NMRI). An MRI of the spine and pelvis may be used to find areas where the bone is damaged.

• PET scan (positron emission tomography scan): A procedure to find malignant tumor cells in the body. A small amount of radioactive glucose (sugar) is injected into a vein. The PET scanner rotates around the body and makes a picture of where glucose is being used in the body. Malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells do.

• CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, such as the spine, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.

• PET-CT scan : A procedure that combines the pictures from a positron emission tomography (PET) scan and a computed tomography (CT) scan. The PET and CT scans are done at the same time with the same machine. The combined scans give more detailed pictures of areas inside the body, such as the spine, than either scan gives by itself.

Certain factors affect prognosis (chance of recovery) and treatment options.

The prognosis (chance of recovery) depends on the following:

• The type of plasma cell neoplasm.

• The stage of the disease.

• Whether a certain immunoglobulin (antibody) is present.

• Whether there are certain genetic changes.

• Whether the kidney is damaged.

• Whether the cancer responds to initial treatment or recurs (comes back).

Treatment options depend on the following:

• The type of plasma cell neoplasm.

• The age and general health of the patient.

• Whether there are signs, symptoms, or health problems, such as kidney failure or infection, related to the disease.

• Whether the cancer responds to initial treatment or recurs (comes back).

Stages of Plasma Cell Neoplasms

KEY POINTS

• There are no standard staging systems for monoclonal gammopathy of undetermined significance (MGUS), macroglobulinemia, and plasmacytoma.

• After multiple myeloma has been diagnosed, tests are done to find out the amount of cancer in the body.

• The stage of multiple myeloma is based on the levels of beta-2-microglobulin and albumin in the blood.

• The following stages are used for multiple myeloma:

  • Stage I multiple myeloma

  • Stage II multiple myeloma

  • Stage III multiple myeloma

There are no standard staging systems for monoclonal gammopathy of undetermined significance (MGUS), macroglobulinemia, and plasmacytoma.

After multiple myeloma has been diagnosed, tests are done to find out the amount of cancer in the body.

The process used to find out the amount of cancer in the body is called staging. It is important to know the stage in order to plan treatment. The following tests and procedures may be used in the staging process:

• Skeletal bone survey: In a skeletal bone survey, x-rays of all the bones in the body are taken. The x-rays are used to find areas where the bone is damaged. An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body.

• MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body, such as the bone marrow. This procedure is also called nuclear magnetic resonance imaging (NMRI).

• Bone densitometry: A procedure that uses a special type of x-ray to measure bone density.

The stage of multiple myeloma is based on the levels of beta-2-microglobulin and albumin in the blood.

Beta-2-microglobulin and albumin are found in the blood. Beta-2-microglobulin is a protein found on plasma cells. Albumin makes up the biggest part of the blood plasma. It keeps fluid from leaking out of blood vessels. It also brings nutrients to tissues, and carries hormones, vitamins, drugs, and other substances, such as calcium, all through the body. In the blood of patients with multiple myeloma, the amount of beta-2-microglobulin is increased and the amount of albumin is decreased.

The following stages are used for multiple myeloma:

Stage I multiple myeloma

In stage I multiple myeloma, the blood levels are as follows:

• beta-2-microglobulin level is lower than 3.5 mg/L; and

• albumin level is 3.5 g/dL or higher.

Stage II multiple myeloma

In stage II multiple myeloma, the blood levels are in between the levels for stage I and stage III.

Stage III multiple myeloma

In stage III multiple myeloma, the blood level of beta-2-microglobulin is 5.5 mg/L or higher and the patient also has one of the following:

• high levels of lactate dehydrogenase (LDH); or

• certain changes in the chromosomes.

Refractory Plasma Cell Neoplasms

Plasma cell neoplasms are called refractory when the number of plasma cells keeps going up even though treatment is given.

Treatment Option Overview

KEY POINTS

• There are different types of treatment for patients with plasma cell neoplasms.

• Eight types of treatment are used:

  • Chemotherapy

  • Other drug therapy

  • Targeted therapy

  • High-dose chemotherapy with stem cell transplant

  • Biologic therapy

  • Radiation therapy

  • Surgery

  • Watchful waiting

• New types of treatment are being tested in clinical trials.

  • New combinations of therapies

• Treatment for plasma cell neoplasms may cause side effects.

• Supportive care is given to lessen the problems caused by the disease or its treatment.

• Patients may want to think about taking part in a clinical trial.

• Patients can enter clinical trials before, during, or after starting their cancer treatment.

• Follow-up tests may be needed.

There are different types of treatment for patients with plasma cell neoplasms.

Different types of treatments are available for patients with plasma cell neoplasms. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.

Eight types of treatment are used:

Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid, an organ, or a body cavitysuch as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). The way the chemotherapy is given depends on the type and stage of the cancer being treated.

Other drug therapy

Corticosteroids are steroids that have antitumor effects in multiple myeloma.

Targeted therapy

Targeted therapy is a treatment that uses drugs or other substances to identify and attack specific cancer cells without harming normal cells. Several types of targeted therapy may be used to treat multiple myeloma and other plasma cell neoplasms.

Proteasome inhibitor therapy is a cancer treatment that blocks the action of proteasomes in cancer cells. A proteasome is a protein that removes other proteins no longer needed by the cell. When the proteins are not removed from the cell, they build up and may cause the cancer cell to die. Bortezomib, carfilzomib, and ixazomib are proteasome inhibitors used in the treatment of multiple myeloma and other plasma cell neoplasms.

Monoclonal antibody therapy is a cancer treatment that uses antibodies made in the laboratory, from a single type of immune system cell. These antibodies can identify substances on cancer cells or normal substances that may help cancer cells grow. The antibodies attach to the substances and kill the cancer cells, block their growth, or keep them from spreading. Monoclonal antibodies are given by infusion. They may be used alone or to carry drugs, toxins, or radioactive material directly to cancer cells. Daratumumab and elotuzumab are monoclonal antibodies used in the treatment of multiple myeloma and other plasma cell neoplasms.

Histone deacetylase (HDAC) inhibitor therapy is a type of targeted therapy that blocks enzymes needed for cell division and may stop the growth of cancer cells. Panobinostat is an HDAC inhibitor used in the treatment of multiple myeloma and other plasma cell neoplasms.

High-dose chemotherapy with stem cell transplant

This treatment is a way of giving high doses of chemotherapy and replacing blood -forming cells destroyed by the cancer treatment. Stem cells (immature blood cells) are removed from the blood or bone marrow of the patient (autologous transplant) or a donor (allogeneic transplant) and are frozen and stored. After the chemotherapy is completed, the stored stem cells are thawed and given back to the patient through an infusion. These reinfused stem cells grow into (and restore) the body's blood cells.

Biologic therapy

Biologic therapy is a treatment that uses the patient's immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body's natural defenses against cancer. This type of cancer treatment is also called biotherapy or immunotherapy.

Immunomodulators are a type of biologic therapy. Thalidomide, lenalidomide, and pomalidomide are immunomodulators used to treat multiple myeloma and other plasma cell neoplasms.

Interferon is a type of biologic therapy. It affects the division of cancer cells and can slow tumor growth.

Radiation therapy

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy:

• External radiation therapy uses a machine outside the body to send radiation toward the cancer.

• Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer.

The way the radiation therapy is given depends on the type and stage of the cancer being treated. External radiation therapy is used to treat plasma cell neoplasms.

Surgery

Surgery to remove the tumor may be done. After the doctor removes all the cancer that can be seen at the time of the surgery, some patients may be given radiation therapy after surgery to kill any cancer cells that are left. Treatment given after the surgery, to lower the risk that the cancer will come back, is called adjuvant therapy.

Watchful waiting

Watchful waiting is closely monitoring a patient’s condition without giving any treatment until signs or symptoms appear or change.

New types of treatment are being tested in clinical trials.

This summary section describes treatments that are being studied in clinical trials. It may not mention every new treatment being studied. Information about clinical trials is available from the NCI website.

New combinations of therapies

Clinical trials are studying different combinations of biologic therapy, chemotherapy, steroid therapy, and drugs. New treatment regimens using thalidomide or lenalidomide are also being studied.

Treatment for plasma cell neoplasms may cause side effects.

For information about side effects caused by treatment for cancer, see our Side Effects page.

Supportive care is given to lessen the problems caused by the disease or its treatment.

This therapy controls problems or side effects caused by the disease or its treatment and improves quality of life. Supportive care is given to treat problems caused by multiple myeloma and other plasma cell neoplasms.

Supportive care may include the following:

• Plasmapheresis: If the blood becomes thick with extra antibody proteins and interferes with circulation, plasmapheresis is done to remove extra plasma and antibody proteins from the blood. In this procedure blood is removed from the patient and sent through a machine that separates the plasma (the liquid part of the blood) from the blood cells. The patient's plasma contains the unneeded antibodies and is not returned to the patient. The normal blood cells are returned to the bloodstream along with donated plasma or a plasma replacement. Plasmapheresis does not keep new antibodies from forming.

• High-dose chemotherapy with stem cell transplant: If amyloidosis occurs, treatment may include high-dose chemotherapy followed by stem cell transplant using the patient's own stem cells.

• Biologic therapy: Biologic therapy with thalidomide, lenalidomide, or pomalidomide is given to treat amyloidosis.

• Targeted therapy: Targeted therapy with proteasome inhibitors is given to decrease how much immunoglobulin M is in the blood and treat amyloidosis.

• Radiation therapy: Radiation therapy is given for bone lesions of the spine.

• Chemotherapy: Chemotherapy is given to reduce back pain from osteoporosis or compression fractures of the spine.

• Bisphosphonate therapy: Bisphosphonate therapy is given to slow bone loss and reduce bone pain. See the following PDQ summaries for more information on bisphosphonates and problems related to their use:

  • Cancer Pain

  • Oral Complications of Chemotherapy and Head/Neck Radiation

Patients may want to think about taking part in a clinical trial.

For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.

Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.

Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.

Follow-up tests may be needed.

Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests.

Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.

Treatment Options for Plasma Cell Neoplasms

Monoclonal Gammopathy of Undetermined Significance

Treatment of monoclonal gammopathy of undetermined significance (MGUS) is usually watchful waiting. Regular blood tests to check the level of M protein in the blood and physical exams to check for signs or symptoms of cancer will be done.

Isolated Plasmacytoma of Bone

Treatment of isolated plasmacytoma of bone is usually radiation therapy to the bone lesion.

Extramedullary Plasmacytoma

Treatment of extramedullary plasmacytoma may include the following:

• Radiation therapy to the tumor and nearby lymph nodes.

• Surgery usually followed by radiation therapy.

• Watchful waiting after initial treatment, followed by radiation therapy, surgery, or chemotherapy if the tumor grows or causes signs or symptoms.

Multiple Myeloma

Patients without signs or symptoms may not need treatment. When signs or symptoms appear, the treatment of multiple myeloma may be done in phases:

• Induction therapy: This is the first phase of treatment. Its goal is to reduce the amount of disease, and may include one or more of the following:

  • Corticosteroid therapy.

  • Biologic therapy with lenalidomide, pomalidomide, or thalidomide therapy.

  • Targeted therapy with proteasome inhibitors (bortezomib, carfilzomib, and ixazomib) or monoclonal antibodies (daratumumab and elotuzumab).

  • Chemotherapy.

  • Histone deacetylase inhibitor therapy with panobinostat.

  • A clinical trial of different combinations of treatment.

• Consolidation chemotherapy: This is the second phase of treatment. Treatment in the consolidation phase is to kill any remaining cancer cells. High-dose chemotherapy is followed by either:

  • one autologous stem cell transplant, in which the patient's stem cells from the blood or bone marrow are used; or

  • two autologous stem cell transplants followed by an autologous or allogeneic stem cell transplant, in which the patient receives stem cells from the blood or bone marrow of a donor; or

  • one allogeneic stem cell transplant.

• Maintenance therapy: After the initial treatment, maintenance therapy is often given to help keep the disease in remission for a longer time. Several types of treatment are being studied for this use, including the following:

  • Chemotherapy.

  • Biologic therapy with interferon.

  • Corticosteroid therapy.

  • Lenalidomide therapy.

  • Targeted therapy with a proteasome inhibitor (bortezomib).

Refractory Multiple Myeloma

Treatment of refractory multiple myeloma may include the following:

• Watchful waiting for patients whose disease is stable.

• A different treatment than treatment already given, for patients whose tumor kept growing during treatment. (See Multiple Myeloma treatment options.)

• A clinical trial of a new therapy.

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