Multiple Myeloma

Medically Reviewed By William C. Lloyd III, MD, FACS
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What is multiple myeloma?

Multiple myeloma is a type of blood cancer that begins in the bone marrow and represents a cancer of the plasma cell, a particular type of lymphoid cell. Healthy plasma cells are like small factories that produce abundant antibodies. In myeloma, there is an unregulated proliferation of plasma cells from the bone marrow, clogging the body’s circulatory system with excess, meaningless (nonfunctional) antibodies. Eventually, the cancer cells move from the bone marrow and spread throughout the body. This makes the disease particularly hard to treat, since there is not a solid tumor to target.

Some myelomas, called smoldering myelomas, do not cause symptoms and may not need immediate treatment. If treatment is delayed, careful follow-up is important so treatment can be started as soon as significant progression or symptoms become apparent. While multiple myeloma is not curable, treatment can often control disease progression and symptoms.

Multiple myeloma can interfere with production of new blood cells in the bone marrow, which can result in anemia, increased risk of infection, and easy bruising and bleeding. It also produces a substance that weakens bones and abnormal proteins, including monoclonal (M) protein, that can cause kidney damage and other problems.

Multiple myeloma is not a very common cancer; approximately 20,000 people are diagnosed with multiple myeloma each year in the United States. The cause of multiple myeloma is not known, but it is most common in people over the age of 50 and in African Americans.

Because multiple myeloma can decrease production of new blood cells, people who have it can have problems with bleeding and serious infections. Seek immediate medical care (call 911) for uncontrolled bleeding, severe sweating, severe difficulty breathing, pale or blue lips, fast heart rate, confusion, or loss or change in level of consciousness.

Seek prompt medical care if you have experienced unexpected weight loss, persistent fever, frequent infections, night sweats, tiredness, or bone pain.

What are the different types of multiple myeloma?

The two main types of multiple myeloma are smoldering and active:

  • Smoldering myeloma is typically asymptomatic, but there are some laboratory findings: More than 10% of the cells in the bone marrow are plasma cells—compared to 1% normally—and the M protein they secrete into the blood is 30 g/L or higher. Oncologists may delay treatment for smoldering myeloma, depending on the genetic characteristics of the abnormal plasma cells. This type of myeloma is also known as indolent myeloma or asymptomatic myeloma. 
     
  • Active myeloma is symptomatic. In addition, medical tests show kidney and bone damage and low blood cell counts, including low red blood cells. Doctors may diagnose active myeloma based on the subtype of the abnormal plasma cells; certain cell markers predict progression of smoldering to active form of disease within 18 to 24 months.  

What are the symptoms of multiple myeloma?

Multiple myeloma may produce a variety of symptoms or none at all.

Common symptoms of multiple myeloma

Symptoms that can be experienced with multiple myeloma include:

Serious symptoms that might indicate a life-threatening condition

In some cases, multiple myeloma or its complications can be life-threatening. Seek immediate medical care (call 911) if you, or someone you are with, have any of these life-threatening symptoms:

What causes multiple myeloma?

The specific cause of multiple myeloma is not known, but cancer biologists believe several factors play a role in its development. As with other cancers, changes (mutations) in specific types of genes can cause cells to become cancerous and grow uncontrollably. With multiple myeloma, it is a plasma cell in the bone marrow that grows out of control and becomes a myeloma cell. The cell multiplies and, with time, the myeloma cells accumulate more changes that give them the ability to spread from the bone marrow to other areas of the body, forming tumors. People with active multiple myeloma develop tumors in more than one location in the bone marrow and elsewhere in the body.

In about half of all people with myeloma, part of one chromosome has switched with part of another chromosome in the myeloma cells. This is called a translocation. When this occurs in a crucial area next to a proto-oncogene (a gene that has potential to cause cancer), it can promote abnormal plasma cell growth.

Researchers have found that patients with plasma cell tumors have important abnormalities in other bone marrow cells too, and that these abnormalities may also cause excess plasma cell growth. Certain cells in the bone marrow called dendritic cells release a hormone called interleukin-6 (IL-6), which stimulates normal plasma cells to grow. Excessive production of IL-6 by these cells appears to be an important factor in development of plasma cell tumors.

Multiple myeloma is not considered an inherited condition. Rather, the cancer-causing changes develop during one’s lifetime. Most people who develop myeloma are older than 65. However, myeloma tends to run in families, so there may be some hereditary factors yet to be identified. In addition to older age, multiple myeloma is more common among Black males.

What are the risk factors for multiple myeloma?

A number of factors increase the risk of developing multiple myeloma. Not all people with risk factors will get multiple myeloma. Risk factors for multiple myeloma include:

  • African American ethnicity. Black people have twice the rate of myeloma as white people.

  • Age older than 65

  • Chemical exposure, such as benzene or Agent Orange

  • Family history of multiple myeloma

  • Male biological sex

  • Monoclonal gammopathy of undetermined significance (MGUS), an abnormal protein of plasma cells. Annually, 1 out of 100 people with MGUS develop cancer like myeloma or lymphoma

  • Obesity

  • Radiation exposure, either from previous cancer treatment or by accident

How do you prevent multiple myeloma?

Multiple myeloma is a type of cancer that most likely develops by chance, but you may be able to reduce your risk by protecting yourself from exposure to known cancer-causing chemicals (such as benzene) and radiation. The risk of multiple myeloma increases with age. It is also more common among African Americans and men. People with a family history of myeloma have a greater risk of developing it.

If you have risk factors for myeloma, you may want to talk with your doctor about the benefits and risks of regular blood work to monitor your blood health as you age.

What are some conditions related to multiple myeloma?

Myeloma-related conditions include:

  • Monoclonal gammopathy of undetermined significance (MGUS), a precancerous condition characterized by an increased level of an abnormal monoclonal antibody—M protein—in the blood. About 1 in 100 people with MGUS develop myeloma, so they have periodic blood tests to monitor the condition.
  • Waldenström’s macroglobulinemia, a very rare form of non-Hodgkin lymphoma (cancer of immature white blood cells). In some cases, MGUS can develop into Waldenstrom’s. 
  • Solitary plasmacytoma is a single plasma cell tumor growing in one area, such as a lung or in the throat. People with a solitary plasmacytoma do not have abnormal plasma cells accumulating in the bone marrow.
  • Systemic amyloidosis is characterized by an abnormal protein called amyloid in tissues throughout the body. Similar to multiple myeloma, accumulation of the abnormal protein damages organs and can lead to organ failure. 

How do doctors diagnose multiple myeloma?

It can take a long time before myeloma is discovered. Occasionally, doctors discover it by accident, through a routine blood test or because you have a fracture and the X-rays show unusual findings. Generally, healthcare professionals diagnose multiple myeloma by the symptoms it is causing and the results of some or all of these tests:

  • Blood tests to measure your red blood cells, white blood cells, and platelets; blood calcium; and M protein, an abnormal antibody that can thicken the blood; as well as other blood components.

  • Urine tests to determine how well your kidneys are functioning. (Myeloma-induced hypercalcemia damages the kidneys.)

  • X-rays and other imaging tests, such as magnetic resonance imaging (MRI), computed tomography scans (CT), and positron emission tomography (PET) scans, to examine bone structure and look for areas of weak bone

  • Bone marrow aspiration or bone marrow biopsy to check for cancer cells

Multiple myeloma diagnostic criteria include:

  • Anemia (low red blood cell count)

  • Bony lesions

  • Focal areas of malignant cells by MRI

  • Hypercalcemia (high levels of calcium in the blood)

  • Kidney failure

  • Malignant plasma cells make up at least 10% of cells in the bone marrow

  • Plasma cells make up at least 60% of cells in bone marrow

Once you have a diagnosis of multiple myeloma, your oncologist will stage it, which indicates how advanced the disease is. The doctor will analyze the myeloma cells for genetic changes, which can help determine how quickly the myeloma will progress and what treatment options may be most effective.

What are the stages of multiple myeloma?

Oncologists classify active myeloma into a specific stage, which helps determine treatment options and prognosis. Doctors use the Revised International Staging System (RISS) to assign myeloma to stage I, II or III. The levels of certain plasma cell proteins in the blood and chromosome abnormalities of the malignant plasma cells define the stage:

  • Albumin (serum albumin) 

  • Beta-2-microglobulin (beta2-M) 

  • Lactase dehydrogenase (LDH)

  • Chromosome abnormalities

Stage I has a better prognosis than stage II and III, which has a worse prognosis. The features of each stage are as follows

  • Stage I: Albumin 3.5 g/dL or greater, beta2-M is less than 3.5 mg/L, LDH is normal, and chromosome abnormalities are not high-risk for multiple myeloma

  • Stage II: not stage I or III

  • Stage III: Beta2-M is 5.5 mg/L or higher and chromosome abnormalities are considered high-risk

How is multiple myeloma treated?

The need for multiple myeloma treatment depends on whether or not you are experiencing symptoms. People without symptoms may not need myeloma treatment. Instead, their doctors may monitor the disease for signs it is progressing. This is watchful waiting.

However, people at high risk for disease progression may need to start treatment before symptoms develop. Typically, doctors advise people with increased calcium levels, kidney problems, anemia, and bone damage to begin treatment right away. Treatment is also recommended when more than 60% of the bone marrow cells are abnormal plasma cells.

The goal of multiple myeloma treatment is to bring about a complete remission of the disease. Remission means there is no longer any sign of the disease in the body, although it may recur or relapse later.

Once you and your doctor make the decision to start treatment for multiple myeloma, it typically goes in phases:

  • Induction therapy is the first phase of treatment. The goal is to quickly control the cancer and kill as many cancer cells as possible.

  • Consolidation therapy comes after induction therapy. The goal is to eliminate any remaining cancer cells.

  • Maintenance therapy is the third phase. The goal is to keep the disease in remission for as long as possible.

It is important to continue regular visits with your medical care team so significant progression or relapse can be identified early, and to watch for and treat any complications that might result from the disease or its treatments.

There are many approaches to treating multiple myeloma; the specific approach taken will depend on the stage of the disease, what symptoms are present, whether kidney damage has occurred, and whether any other health problems exist.

Treatment approaches include:

  • Chemotherapy to attack cancer cells

  • Targeted therapy to limit the production of new cancer cells

  • Immunotherapy 

  • Participation in a clinical trial testing promising new treatments for multiple myeloma

  • Radiation therapy to help control pain and reduce fracture risk

  • Stem cell transplant to provide healthy stem cells that can make new blood cells

  • Steroids to slow growth of cancer cells and enhance other therapies

  • Watchful waiting to identify when to start treatment

Here’s a closer look at each type of therapy:

Chemotherapy

Chemotherapy—or chemo—uses powerful drugs to kill cancer cells, or stop or slow their growth. These drugs travel through the bloodstream to find cancer cells everywhere in the body. This makes chemo very useful for treating multiple myeloma.

However, chemo is not selective—meaning it does not only kill cancer cells. Chemo drugs will kill any rapidly multiplying cell. This includes some types of normal cells, such as hair follicles and the lining of the digestive tract. Many of the side effects of chemo are the result of this action.

Multiple myeloma chemotherapy is usually part of all three phases of treatment. There are a variety of chemo drugs to treat multiple myeloma, including:

  • Bendamustine (Treanda)

  • Carmustine (BiCNU)

  • Cisplatin (Platinol)

  • Cyclophosphamide (Cytoxan, Neosar)

  • Doxorubicin (Adriamycin, Doxil)

  • Etoposide (Toposar, VePesid)

  • Melphalan (Alkeran)

  • Vincristine (Oncovin)

You typically take more than one chemo drug in cycles that last for a few weeks. Doctors may also use corticosteroids in combination with chemo.

Targeted Therapy

Unlike traditional chemotherapy, targeted therapy is selective. It works by using specific markers or characteristics unique to cancer cells. This often means fewer and less severe side effects. This therapy may also work when standard chemo does not. Targeted treatments can be useful during induction therapy and maintenance therapy.

The drugs in this group represent some of the newest treatments for multiple myeloma:

  • Histone deacetylase (HDAC) inhibitors target a specific enzyme. Panobinostat (Farydak) is in this class.

  • Monoclonal antibodies attack a target on myeloma cells. Elotuzumab (Empliciti) and daratumumab (Darzalex) are in this class.

  • Proteasome inhibitors target certain enzymes (proteasomes) and help control cell division. This class includes bortezomib (Velcade), carfilzomib (Kyprolis), and ixazomib (Ninlaro).

Immunotherapy

Immunotherapy—or biologic therapy—for multiple myeloma modulates the immune system to help fight cancer. These multiple myeloma drugs can boost the immune system to find and kill cancer cells better. Doctors use this kind of therapy for both induction and maintenance phases.

Drugs in this class include:

  • Immunomodulators including lenalidomide (Revlimid), pomalidomide (Pomalyst), and thalidomide (Synovir, Thalomid)

  • Interferons, which are proteins that boost overall immune system function

Stem Cell Transplant

Consolidation therapy for multiple myeloma involves high-dose chemotherapy. This treatment destroys the bone marrow where the myeloma cells grow. However, it can lead to life-threatening complications because you need your bone marrow to make new blood cells. So, it is necessary to restore the body’s ability to make new blood cells.

A stem cell transplant accomplishes this goal. With today’s technology, doctors collect your stem cells before high-dose chemo and freeze them for transplantation afterwards.

Other treatments for multiple myeloma

Other therapies may be added to help with your general state of health and any complications of the cancer or its treatment including:

  • Antinausea medications

  • Bisphosphonates to help strengthen bones. Drugs include zoledronic acid (Zometa) and pamidronate (Aredia). An alternative option is denosumab (Xgeva). It works differently, but is equally effective.

  • Blood transfusions to correct anemia or low platelets

  • Corticosteroids to inhibit plasma cells and reduce inflammation

  • Dietary counseling to help maintain strength and nutritional status

  • Intravenous fluids to help flush excess calcium out of the bloodstream

  • IVIG (intravenous immunoglobulin) gives antibodies through a vein to help fight or prevent infections. This may be necessary when blood tests show low levels of normal antibodies.

  • Pain medications if needed to increase comfort

  • Plasmapheresis to remove excess removes excessive amounts of M protein from the blood. This may be necessary when the blood becomes too thick with the protein, a condition called hyperviscosity. This can interfere with adequate blood flow.

  • Radiation therapy to treat bone pain in isolated areas

  • Surgery to support weakened bones or treat bone fractures

Complementary treatments

Some complementary treatments may help some people to better deal with multiple myeloma and its treatments. These treatments, sometimes referred to as alternative therapies, are used in conjunction with traditional medical treatments. Complementary treatments are not meant to substitute for traditional medical care. Be sure to notify your doctor if you are consuming nutritional supplements or homeopathic (nonprescription) remedies as they may interact with the prescribed medical therapy.

Complementary treatments may include:

  • Acupuncture

  • Massage therapy

  • Nutritional dietary supplements, herbal remedies, tea beverages, and similar products. (There is no evidence of dietary supplements having an effect on cancer remission or recurrence)

  • Yoga

Hospice care

In cases in which multiple myeloma has progressed to an advanced stage and has become unresponsive to treatment, the goal of treatment may shift away from controlling the disease and focus on measures to keep a person comfortable and maximize the quality of life. Hospice care involves medically controlling pain and other symptoms while providing psychological and spiritual support to the patient, as well as services to support loved ones.

Considering your treatment options

The treatment that is best for you depends on your symptoms and your overall health. Talk with your doctor about the goals, benefits, and side effects of multiple myeloma treatment. Being informed will help you make the best decision for you.

How does multiple myeloma affect quality of life?

Multiple myeloma is a rare cancer, but one that usually becomes a chronic condition requiring long-term treatment. Fatigue, pain and reduced physical function are the most important determinants of health-related quality of life for people with multiple myeloma. Treatment improvements (such as certain drug combinations) are allowing patients to undergo treatment longer with fewer side effects, which also improves life expectancy with multiple myeloma. All of this translates into better quality of life for these patients.

Coping tips and lifestyle changes

Living with a chronic condition, especially cancer can be very stressful, which can decrease quality of life. These coping tips may help:

  • Develop a plan of action with your care team, such as a schedule of appointments for the next six months, tests you may need, and when to call the doctor or nurse for symptoms. 
  • Get active with friends, acquaintances or family members. Stay as social as possible.
      
  • Inform your care team about any side effects from treatment. There are many options for addressing treatment side effects. There may also be a different medication option with fewer side effects. 
  • Join a myeloma support group, either online or in-person, where you can connect with others who may be experiencing the same type of challenges as you.
  • Work with a dietitian to develop delicious and nutritious meals that will entice you to eat. (Some myeloma treatments can decrease appetite.)

What are the potential complications of multiple myeloma?

Complications of untreated or poorly controlled multiple myeloma can be serious, even life-threatening in some cases. You can help minimize your risk of serious complications by following the treatment plan you and your healthcare professional design specifically for you. Complications of multiple myeloma include:

  • Adverse effects of multiple myeloma treatment

  • Amyloidosis (rare immune-related disorder characterized by protein buildup in organs and tissues that can cause serious complications)

  • Anemia (low red blood cell count)

  • Broken bones, including compression fracture

  • Hypercalcemia (increased calcium in the blood)

  • Hyperviscosity syndrome (thickened blood that is difficult for the heart to pump)

  • Immune deficiency and frequent infections

  • Kidney failure due to extra calcium in the bloodstream as bones weaken

  • Osteoporosis

  • Spread of cancer

What is the survival rate and prognosis for multiple myeloma?

Your multiple myeloma prognosis—the chance of remission—depends on how far the cancer has progressed, how quickly it grows (or is likely to grow), the response to treatment, and your age and overall health, among other factors. In general, the farther the disease has spread the poorer the prognosis. But, some people live for many years with myeloma. It might go away, then come back, then go into remission again with a different type of treatment. Your doctor can discuss your prognosis with you based on your test results and treatment options.

Survival rates for multiple myeloma are only estimates, based on what happened to myeloma patients in past years. They are five-year relative survival rates, which means they compare people with myeloma to people of the same age without it. For example, a five-year relative survival rate of 80% means that, on average, people diagnosed with multiple myeloma are 80% as likely as someone without it to live at least five years after diagnosis.

The following five-year relative survival rates come from the SEER (Surveillance, Epidemiology, and End Results) database, which stages myeloma as localized or distant. The rates are based on people diagnosed with a plasmacytoma or multiple myeloma between 2010 and 2016:

  • Localized, a solitary tumor (plasmacytoma): 75%

  • Distant, multiple plasmacytomas inside or outside bones: 53%

Most people (95%) are diagnosed with distant (multiple) myeloma. Multiple myeloma cannot be cured, but newer treatments are improving life expectancy after diagnosis. Following your treatment plan may help relieve symptoms and the disease’s progression. Attending all follow-up visits with your medical team can help identify problems associated with the disease, allowing for treatment adjustments as needed.

Multiple myeloma awareness

Multiple myeloma is not common: The National Cancer Institute estimates 32,000 people in the United States were diagnosed with multiple myeloma in 2020 (compared to more than 200,000 lung cancer diagnoses). Researchers are learning more everyday about what causes myeloma and the best ways to treat it. Survival rates will continue to improve with different and new combinations of treatments.

March is Multiple Myeloma Awareness month.

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Medical Reviewer: William C. Lloyd III, MD, FACS
Last Review Date: 2021 Aug 28
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THIS TOOL DOES NOT PROVIDE MEDICAL ADVICE. It is intended for informational purposes only. It is not a substitute for professional medical advice, diagnosis or treatment. Never ignore professional medical advice in seeking treatment because of something you have read on the site. If you think you may have a medical emergency, immediately call your doctor or dial 911.
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