Multiple Myeloma

  • Medical Author:
    Charles Patrick Davis, MD, PhD

    Dr. Charles "Pat" Davis, MD, PhD, is a board certified Emergency Medicine doctor who currently practices as a consultant and staff member for hospitals. He has a PhD in Microbiology (UT at Austin), and the MD (Univ. Texas Medical Branch, Galveston). He is a Clinical Professor (retired) in the Division of Emergency Medicine, UT Health Science Center at San Antonio, and has been the Chief of Emergency Medicine at UT Medical Branch and at UTHSCSA with over 250 publications.

  • Medical Editor: William C. Shiel Jr., MD, FACP, FACR
    William C. Shiel Jr., MD, FACP, FACR

    William C. Shiel Jr., MD, FACP, FACR

    Dr. Shiel received a Bachelor of Science degree with honors from the University of Notre Dame. There he was involved in research in radiation biology and received the Huisking Scholarship. After graduating from St. Louis University School of Medicine, he completed his Internal Medicine residency and Rheumatology fellowship at the University of California, Irvine. He is board-certified in Internal Medicine and Rheumatology.

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Multiple myeloma facts

  • Multiple myeloma is a cancer of the plasma cells in the bone marrow.
  • The cause of multiple myeloma is not known.
  • Risk factors for multiple myeloma have not been established although researchers have suggested genetic abnormalities, such as c-Myc genes or environmental exposures, may play a role.
  • Symptoms and signs of multiple myeloma include
  • Multiple myeloma is diagnosed with a bone marrow aspiration and/or biopsy. Other tests include blood monoclonal immunoglobulin and radiology tests to determine the extent of bone lesions.
  • Although there are several staging systems, stages I, II, and III usually represent multiple myeloma with increasing severity of disease.
  • Treatment for multiple myeloma includes drugs that modulate the immune system, chemotherapy drugs, radiation therapy, stem cell transplants and, in some patients, surgery.
  • Although the patient's primary care physician is involved in organizing treatments, specialists who treat multiple myeloma include oncologists, hematologists, radiologists, experts in stem cell transplantation and orthopedic and/or spine surgeons.
  • The prognosis for myeloma is only fair. Median survival is about three years, but some patients have a life expectancy of 10 years.
  • The International Myeloma Foundation can provide further support for myeloma patients.

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Multiple Myeloma Symptoms

Multiple myeloma is a cancer of certain cells of the bone marrow called plasma cells. Multiple myeloma is a form of bone marrow cancer. Plasma cells normally produce our antibodies. Multiple myeloma features abnormal proliferation of plasma cells in the bone marrow, destructive bone lesions, and the production of abnormal proteins, specifically antibodies. Multiple myeloma is also referred to as myeloma.

Multiple myeloma causes a host of organ problems and symptoms. Common symptoms of multiple myeloma include:

  • fatigue,
  • bone pain,
  • bone fracture,
  • susceptibility to infection,
  • kidney failure.

What is multiple myeloma? What are plasma cells?

Multiple myeloma definition

Multiple myeloma is a type of cancer of the plasma cells of the bone marrow. These are protein-making cells that normally make all of the different kinds of antibodies of the immune system. In multiple myeloma, the plasma cells undergo what is referred to as a malignant transformation and become cancerous. These myeloma cells stop making different forms of protein in response to the immune system's needs and instead start to produce a single abnormal type of protein, a monoclonal or M protein. Multiple myeloma plasma cell populations accumulate in the bone marrow and these collections of cells called plasmacytomas can erode the hard outer shell or cortex of the bone that normally surrounds the marrow. These weakened bones show thinning of the bone such as is seen in nonmalignant osteoporosis or what appear to be punched out or lytic bone lesions. These lesions may cause pain and even breaks or fractures of the weakened bones. They may cause other systemic problems listed below. Multiple myeloma is often referred to simply as myeloma (also termed Kahler's disease after the physician who first described this cancer). The disease usually occurs in people past middle-age. However, rarely it is possible to occur in a child.

What causes multiple myeloma?

What triggers the malignancy of plasma cells in multiple myeloma is not known. The cancerous myeloma plasma cells proliferate and crowd out normal plasma cells and can etch away areas of bones. The proteins produced in large amounts can cause many of the symptoms of the disease by making the blood more thickened (viscous) and depositing the proteins in organs that can interfere with the functions of the kidneys, nerves, and immune system.

What are risk factors for multiple myeloma? Is multiple myeloma hereditary?

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 so it is not considered to be a hereditary disease. 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 two to 19 years after MGUS diagnosis. In addition, smoldering multiple myeloma (also termed inactive) is an early precursor to multiple myeloma. Abnormal proteins in blood or urine are detectable with special testing before multiple myeloma symptoms occur.

What are multiple myeloma symptoms and signs?

Patients with myeloma may be found asymptomatic with an unexplained increase in protein in the blood. With more advanced disease, some myeloma patients may present with weakness due to anemia caused by inadequate production of red blood cells, with bone pain due to the aforementioned bone damage, and as the abnormal M protein can accumulate in and damage the kidneys thereby resulting in a patient being found to have otherwise unexplained kidney damage and decreased kidney function.

The following is a list symptoms and signs of multiple myeloma:

What tests do health care professionals use to make a diagnosis of multiple myeloma?

In many patients, multiple myeloma is first suspected when a routine blood test shows an abnormal amount of protein in the bloodstream or an unusual stickiness of red blood cells causing them to stack up almost like coins in a pattern called rouleaux, an unusual formation for red blood cells. The health care professional will do a history and physical exam, looking for signs and symptoms (see above) of multiple myeloma. If multiple myeloma is suspected, several studies help confirm the diagnosis. They include a bone marrow aspiration and biopsy most commonly from the large bones of the pelvis. Cells obtained from the marrow are studied by a pathologist to determine if there is one (plasmacytoma) or more (multiple myeloma) abnormal types or numbers of cells. A sample of the bone marrow aspirate is also studied for more detailed characteristics such as the presence or absence of abnormal numbers or types of chromosomes (DNA) by what is called cytogenetic testing. Other molecular testing may be done on the marrow sample as well. The bone marrow biopsy can assess the concentrations of cells in the marrow and the presence of abnormal invasive growth of cellular elements. Blood testing and urine testing by several methods can determine levels and types of monoclonal protein produced. The M protein may be a complete form of a type of antibody called an immunoglobulin (IgG or IgA, for example) or only a portion of the protein called a lambda or kappa light chain. Normal antibodies consist of both heavy and light chain components. In 2011, the National Comprehensive Cancer Network (NCCN) recommended that a serum free light chain assay and fluorescence in situ hybridization (FISH) test be used to further identify multiple myeloma in patients. Most clinicians will use X-ray studies to identify skeletal lesions and MRI for spinal, paraspinal, or spinal cord lesions in multiple myeloma. In addition, several routine tests (CBC, sedimentation rate, BUN, C-reactive protein, and others) are also done.

What types of health care professionals treat multiple myeloma?

Although the patient's primary care doctor helps to manage the patient's care, the specialists involved often include an oncologist, hematology pathologist, radiologist, stem cell transplant specialist, and occasionally a surgeon (orthopedist and/or spine surgeon).

What are the stages of multiple myeloma?

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

  • Smoldering: multiple myeloma with no symptoms
  • Stage I: early disease with little anemia, relatively small amount of M protein and no bone damage
  • Stage II: more anemia and M protein as well as bone damage
  • Stage III: still more M protein, anemia, as well as signs of kidney damage

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 albumin levels; over time this defined criteria may become widely accepted.

What is the medical treatment for multiple myeloma?

There is no known medical treatment that cures multiple myeloma. However, there are methods to decrease the occurrence and severity of symptoms and prolong life. The therapy is decided based upon the patient's condition and the cancer management team, made with the patient's input. The team will likely involve both a medical specialist in the treatment of myeloma called a medical oncologist, as well as a radiation oncologist and other consultants as appropriate. Oncology trained nurses and other personnel will likely be important members of the treatment team.

The choices for treatment(s) often include combinations of drugs, some of which are given as pills and others by intravenous injection. These include drugs which affect or modulate the immune system, steroids, and some oral or injectable chemotherapy drugs. These are usually used in combinations. There may be a role for high-dose chemotherapy followed by the administration of bone marrow stem cells called a stem cell transplant or autotransplantation. Numerous factors come into play in determining whether or not to do such a transplant. Further information may be obtained from the National Comprehensive Cancer Network Guidelines (NCCN.org), which are updated at least yearly. Other medical treatments may include steroids, bisphosphonate therapy, blood or platelet transfusions, autotransplantation and/or plasmapheresis, and other combination therapy depending on the individual patient's disease stage.

Painful areas of bone damage may be treated with radiation therapy. Broken bones can be surgically repaired in many cases.

There are many drugs used to treat multiple myeloma. The following drugs are used often in combination with dexamethasone, sometimes orally or by IV, depending on the patient's individual disease status:

There are at least seven or eight other drugs that are occasionally used alone or in combination with others to aid patients. In addition, some patients with anemia can benefit from blood transfusions although the transfusion effects are temporary. Research is ongoing and newer drugs and drug combinations are being investigated and used for treatment with some frequency. Most health care professionals who specialize in cancer treatment are aware of the newest treatments for multiple myeloma (for example, Procrit, Revlimid, Kyprolis). In addition, your doctor can address the side effects (for example, nausea and vomiting with chemotherapy) that may occur with treatment.

What are lifestyle and diet tips for people with multiple myeloma?

To stay healthy, lifestyle changes can help individuals with multiple myeloma. Giving up tobacco, reducing alcohol intake, eating better, and getting more exercise is recommended. Eating better may be difficult because of changes in your diet and tastes. After multiple myeloma treatments, it can be helpful to eat small meals about two to three hours apart until you feel as if you can eat a larger meal. During treatment, fitness or endurance and muscle strength can decline. For exercise, start slowly by taking short walks or getting involved with an exercise program that gradually increases without pushing the body too hard.

What is the prognosis for multiple myeloma? What is the survival rate for multiple myeloma?

The prognosis of multiple myeloma is variable, depending on the approximate stage and response to therapy. Though there is no cure for the disease, today's treatments are more effective and less toxic (have fewer side effects) than did many in the past. Multiple myeloma is a focus of active ongoing research. The median survival rate, beginning at the point of first treatment according to the American Cancer Society (ACS), according to stage of the disease is as follows:

  • Stage I, 62 months
  • Stage II, 44 months
  • Stage III, 29 months

However, the ACS suggests that with treatment improvements, current survival rates are likely better. Unfortunately, life expectancy after relapse averages about nine months.

Complications of multiple myeloma may include kidney insufficiency, bleeding disorders, bone problems like pathological fractures, hypercalcemia, and neurological problems (for example, spinal cord compression, intracranial plasmacytomas, and others).

Is it possible to prevent multiple myeloma?

Because the risk factors for multiple myeloma are not fully understood, it is not a preventable disease. Currently, there is no cure for the disease. Even some individuals who recommend herbal home remedies like cayenne peppers suggest the herbals are used with drugs. Individuals should discuss the use of home remedies with their doctor before use.

What support systems are available for multiple myeloma?

The International Myeloma Foundation (IMF) can provide caregivers and patients information about many aspects of this disease. IMF's phone number is 1-800-452-2873. There are local, state, and national support groups for multiple myeloma and for palliative care.

What is the latest research on multiple myeloma?

Experimental studies on multiple myeloma have shown that if stem cells from patients with multiple myeloma are grown in cell culture, patients can improve but could also relapse because the stem cells often were contaminated with a few multiple myeloma cells. However, myxoma virus kills human multiple myeloma cells but not stem cells. Consequently, if stem cells for multiple myeloma patients are treated with myxoma viruses, the patient's stem cells are not contaminated multiple myeloma cells. Researchers have used this method to provide multiple myeloma patients with uncontaminated stem cells successfully preventing relapse of multiple myeloma due to contaminated stem cell cultures.

Myxoma viruses exclusively infect rabbit's cells and are not infectious to humans, so the researchers tried another method. In a mouse model of multiple myeloma, the mice were injected with the myxoma viruses and impressively, according to the researchers, 25% of mice had a complete eradication of multiple myeloma and no evidence of relapse. Researchers plan to try to improve this technique in humans and improve the remission rate.

REFERENCES:

American Cancer Society. "Lifestyle Changes After Having Multiple Myeloma." Jan. 19, 2016. <https://www.cancer.org/cancer/multiple-myeloma/after-treatment/lifestyle-changes.html>.

American Cancer Society. "Multiple Myeloma." <http://www.cancer.org/cancer/multiplemyeloma/>.

Bartee, Eric, et al. "Systemic Therapy With Oncolytic Myxoma Virus Cures Established Residual Multiple Myeloma in Mice." Mol Ther Oncolytics 3 (2016): 16032. <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5142464/>.

"Multiple Myeloma Support Groups." The Myeloma Beacon.

"NCCN Guidelines." National Comprehensive Cancer Network.

Fanning, Suzanne R., et al. "Monoclonal gammopathies of uncertain origin." Medscape. 12 Jun 2013.

Shah, Dhaval. "Multiple Myeloma." Medscape.com. Feb. 5, 2016. <http://emedicine.medscape.com/article/204369-overview>.

Last Editorial Review: 2/27/2017

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Reviewed on 2/27/2017
References
REFERENCES:

American Cancer Society. "Lifestyle Changes After Having Multiple Myeloma." Jan. 19, 2016. <https://www.cancer.org/cancer/multiple-myeloma/after-treatment/lifestyle-changes.html>.

American Cancer Society. "Multiple Myeloma." <http://www.cancer.org/cancer/multiplemyeloma/>.

Bartee, Eric, et al. "Systemic Therapy With Oncolytic Myxoma Virus Cures Established Residual Multiple Myeloma in Mice." Mol Ther Oncolytics 3 (2016): 16032. <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5142464/>.

"Multiple Myeloma Support Groups." The Myeloma Beacon.

"NCCN Guidelines." National Comprehensive Cancer Network.

Fanning, Suzanne R., et al. "Monoclonal gammopathies of uncertain origin." Medscape. 12 Jun 2013.

Shah, Dhaval. "Multiple Myeloma." Medscape.com. Feb. 5, 2016. <http://emedicine.medscape.com/article/204369-overview>.

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