Multiple Myeloma

Picture of Different Types of Cancer (Bone Marrow Showing Multiple Myeloma)

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 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 risk factors for multiple myeloma?

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. 

Risk factors for multiple myeloma include:

• Age: The condition is more common in people over 60 years of age
• Race: Multiple myeloma is twice as common in Black people as in White people. It is also more common in people in the Middle East, North Africa, and the Mediterranean than in other parts of the world.
• Multiple myeloma is slightly more common in men.
• Family history is a known risk factor for multiple myeloma, although the genetic mutations linked to the condition are acquired and not inherited.
• Exposure to radiation or chemicals: Exposures known to increase risk of developing multiple myeloma include radiation, asbestos, benzene, pesticides, other chemicals used in rubber manufacturing, wood products, and herbicides.

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.

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:

• Anemia
• Bleeding
• Nerve damage
• Skin lesions (rash)
• Enlarged tongue (macroglossia)
• Bone tenderness or pain, including back pain
• Weakness, fatigue or tiredness
• Infections
• Pathologic bone fractures
• Back pain
• Spinal cord compression
• Kidney failure and/or other end-organ damage
• Loss of appetite and weight loss
• Constipation
• Hypercalcemia
• Leg swelling

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. 

Flurorescence in situ hybridization (FISH) is used to find changes in a person's chromosomes. FISH helps predict whether the myeloma is high risk and aggressive The FISH test is used for most people with myeloma. Other molecular testing can include sequencing of the nucleic acids (DNA and/or RNA) from an individual’s tumor.

Imaging tests that may be used include x-rays, CT scans, MRI, or PET-CT scans. 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.

Staging for multiple myeloma assigns patients to one of 3 stages based on the measurement of serum albumin, lactase dehydrogenase (LDH), and serum beta-2 microglobulin (β2-M) and whether high-risk chromosomes are found using a fluorescence in situ hybridization (FISH) test.

The Revised international staging system (R-ISS) for multiple myeloma is as follows:

Stage I: All of the following apply:

• β2-M less than 3.5 mg/L
• Serum albumin of 3.5 g/dL or more
• Normal LDH
• No high-risk chromosome changes in myeloma cells found by FISH test

Stage II: Not stage I or stage III.

Stage III: β2-M is more than 5.5 mg/L, plus one of the following:

• Myeloma cells have high-risk chromosome changes found by FISH test
• High LDH

However, each individual is unique and may do better or worse than the prediction based on the various stages.

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 as well as targeted therapies that address the specific changes in the individual's tumor. These are usually used in combinations.

For some patients 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. 

Radiation therapy may treat painful areas of bone damage. Surgeons can surgically repair broken bones in many cases.

Immunotherapy, including chimeric antigen receptor (CAR-T) T cell therapy, may be appropriate for some patients. This treatment is designed to use the body’s own immune system to help destroy the cancer cells.

Health care professionals who specialize in cancer treatment are aware of the newest treatments for multiple myeloma. 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. 

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.

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. 

Currently, the five-year survival rate for localized multiple myeloma (one plasmacytoma) is about 79.5 percent, and when multiple tumors are found inside or outside the bones, (classic multiple myeloma) the five-year survival rate  is about 59 percent.

What are the complications of multiple myeloma?

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).

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. Individuals should discuss the use of home remedies with their doctor before use.

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