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Multiple myeloma facts
- Multiple myeloma is a cancer of the plasma cells in the bone marrow.
- Seek medical care for unexplained pain, nausea, vomiting, weight loss, vision problems, or chronic tingling or numbness.
- There is no cure for multiple myeloma. Treatment of multiple myeloma focuses on decreasing the severity of symptoms with medications, stem cell transplants, bisphosphonate therapy, platelet transfusions, and/or plasmapheresis.
The cause of multiple myeloma is unknown. Though there are no known risk factors for multiple myeloma, researchers suggest that genetic abnormalities, such as c-Myc genes or environmental exposures, may play a role.
Symptoms and signs of multiple myeloma include
- bone tenderness,
- bone pain,
- bone fractures,
- kidney damage,
- nerve damage,
- skin lesions,
- enlarged tongue, and
Physicians diagnose multiple myeloma 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.
What is multiple myeloma? What are plasma cells?
Multiple myeloma definition
Multiple myeloma is a type of cancer of the plasma cells (a type of white blood cells) of the bone marrow. Plasma cells are protein-making cells that normally produce the different kinds of antibodies of the disease-fighting immune system. In multiple myeloma, the plasma cells undergo a malignant transformation and become cancerous. These myeloma cells (cancer 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 sometimes termed 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, as 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. People often refer to multiple myeloma 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 can occur in a child.
The National Cancer Institute also notes that one type of myeloma-related plasma cell neoplasm is called a monoclonal gammopathy of undetermined significance (MGUS). In MGUS, medical professionals only find low levels of M protein and people have no symptoms; MGUS infrequently develops into multiple myeloma. Plasma cell neoplasm is another name for multiple myeloma.
What causes multiple myeloma?
What triggers the malignancy of plasma cells in multiple myeloma is unknown. 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. However, triggers or causes related to multiple myeloma may include toxic chemicals, radiation, some viruses, immune disorders, and family history of the disease or other related problems like MGUS.
What are multiple myeloma symptoms and signs?
Patients with myeloma may be asymptomatic with an unexplained increase in protein in the blood. With more advanced disease, some myeloma patients may have 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. Multiple myeloma cancer cells may be in or outside the bone marrow.
The following is a list of symptoms and signs of multiple myeloma:
- Nerve damage
- Skin lesions (rash)
- Enlarged tongue (macroglossia)
- Bone tenderness or pain, including back pain
- Weakness, fatigue or tiredness
- Pathologic bone fractures
- Back pain
- Spinal cord compression
- Kidney failure and/or other end-organ damage
- Loss of appetite and weight loss
- Leg swelling
What are risk factors for multiple myeloma? Is multiple myeloma hereditary?
Medical professionals have not established the definitive cause of multiple myeloma, 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 a hereditary disease. People have suggested environmental exposures to herbicides, insecticides, benzene, hair dyes, and radiation as causes, but definitive data is lacking. Some have suggested inflammation and infection as causes, 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 tests do health care professionals use to make a diagnosis of multiple myeloma?
For many patients, physicians first suspect multiple myeloma 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. Medical professionals also study a sample of the bone marrow aspirate for more detailed characteristics such as the presence or absence of abnormal numbers or types of chromosomes (DNA) by what is called cytogenetic testing. They may perform other molecular testing 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 (for example, serum creatinine) by several methods can determine levels and types of monoclonal protein produced and if there is kidney damage. 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 health care professionals use a serum free light chain assay and fluorescence in situ hybridization (FISH) test 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, medical professionals also perform several routine tests (CBC, sedimentation rate, BUN, C-reactive protein, and others such as beta 2 microglobulin). Bence-Jones proteins, monoclonal polypeptides that compose antibody light chains, may be found in the urine by immunofixation (detection of compounds with antibodies on an electrophoretic gel). Such tests help distinguish between myelomas and lymphomas, such as non-Hodgkin lymphoma and Hodgkin disease.
What specialties 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). Researchers like Avet-Loiseau and others are actively seeking better treatments.
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, these 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 medical professionals give as pills and others by intravenous injection. These include drugs that 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 to do such a transplant. People may obtain further information 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. Also, researchers use meta-analysis (systematically combining data from selected studies to develop a more significant conclusion) of several studies to help determine better treatment protocols for the disease.
Radiation therapy may treat painful areas of bone damage. Surgeons can surgically repair broken bones in many cases.
There are many drugs used to treat multiple myeloma. Medical professionals often use the following drugs in combination with dexamethasone, sometimes orally or by IV, depending on the patient's individual disease status:
- Dexamethasone (Decadron) -- immune cell modulation
- Bortezomib (Velcade) -- protease inhibitor
- Lenalidomide (Revlimid) -- immune cell modulation
- Pamidronic acid (Aredia) -- inhibits bone resorption
- Zoledronic acid (Zometa) -- inhibits bone resorption
- Melphalan (Alkeran) -- alkylating agent that is toxic to myeloma cells
- Carfilzomib (Kyprolis) -- protease inhibitor that is FDA approved usually for patients who have failed a previous treatment
- Daratumumab (Darzalex) -- monoclonal antibody that may damage or kill multiple myeloma cells (and others) that have CD38 protein on their surface
- Elotuzumab (Empliciti) -- a compound that activates the body's natural killer cells to destroy multiple myeloma cells, usually in combination with Revlimid and Decadron
- Ninlaro (Ixazomib) -- This proteasome inhibitor, in combination with Revlimid and dexamethasone, improves the survival rates of some patients with multiple myeloma.
At least seven or eight other drugs that are occasionally used alone or in combination transfusions although the transfusion effects are temporary. Researchers are investigating newer drugs and drug combinations 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. One goal of treatment is progression-free survival; that is the length of time during and after treatment that the patient lives without the symptoms worsening. In addition, low-dose therapy with drugs is being studied in elderly multiple myeloma patients. Risk-adapted therapy is another treatment approach with the design to minimize late disease effects while not compromising the chance for another potential cure.
What are lifestyle and diet tips for people with multiple myeloma?
To stay healthy, lifestyle changes can help individuals with multiple myeloma. Physicians recommend giving up tobacco, reducing alcohol intake, eating better, and getting more exercise. 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 health care professionals do not fully understand the risk factors for multiple myeloma, 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 that patients use the herbals 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, researchers injected the mice 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.
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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/>.
Fanning, Suzanne R., et al. "Monoclonal gammopathies of uncertain origin." Medscape. June 12, 2013.
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