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What is myeloma?
Myeloma is a cancer of plasma cells, a type of white blood cell. Healthy plasma cells are part of the immune system. Plasma cells develop from B cells, a type of white blood cell. Normally when bacteria or viruses enter the body, some B cells mature and change into plasma cells. Plasma cells then make antibodies (also called immunoglobulins) that help the body fight infection.
Myeloma happens when there is a mutation (change) to a single plasma cell, causing it to become a myeloma cell instead of a normal plasma cell. This mutated myeloma cell multiplies into many myeloma cells. As the myeloma cells build up in the bone marrow, they crowd out other types of healthy blood cells. As a result, the body may not have enough healthy red blood cells, white blood cells and platelets.
When myeloma cells build up in the bone marrow, they may form masses called plasmacytomas. These masses can weaken bones and cause pain. The myeloma cells also release substances that break down bones. This causes the bones to become weaker and increases the risk of fractures or breaks.
When myeloma cells damage bones, calcium is released from the bones into the blood. If this happens too quickly, high blood calcium levels can occur. This can cause kidney failure, heart attack or coma.
Myeloma cells make large amounts of abnormal antibodies known as “M” proteins. Other common names for the M protein are “monoclonal protein,” “M spike”, and “paraprotein.”
M proteins are made up of two large pieces called heavy chains and two small pieces called light chains. They do not help fight infection like normal antibodies, and they can also damage the kidneys.
Multiple myeloma
In most patients with myeloma, the disease already involves multiple sites at the time of diagnosis. Because of this, it's often called “multiple myeloma” or “active myeloma.”
What should I do if am diagnosed with myeloma?
- Talk with your doctor about your diagnostic tests and what the results mean.
- Learn how to choose a blood cancer specialist or treatment center.
- Talk with your doctor about all your treatment options and the results you can expect from treatment.
- Ask your doctor whether a clinical trial is a good treatment option for you.
How does myeloma develop?
Myeloma develops when a plasma cell is changed (mutated). Plasma cells are made from B lymphocytes (B cells), a type of white blood cell that is found in the bone marrow. Healthy plasma cells are part of the immune system and make proteins called “antibodies,” which help fight infection.
The mutated plasma cell (myeloma cell) multiplies, and, if untreated, these cells continue to grow in the marrow. They crowd out healthy plasma cells and the normal stem cells in the bone marrow that form white blood cells, red blood cells, and platelets. If left untreated, the cancerous cells can do the following:
- Crowd out functioning white cells so that the immune system can't guard against infection effectively
- Secrete high levels of protein in the blood and urine, which can lead to kidney damage
- Build up in the bone, causing it to weaken, which can lead to bone pain and fractures
What are fisk factors for myeloma?
A “risk factor” is anything that increases a person’s chance of developing a disease. Doctors don't know why some cells become myeloma cells and others don't. For most people who have myeloma, there are no obvious reasons why they developed the disease.
There are some factors that may increase the risk of developing myeloma:
- Age: most people who develop myeloma are over age 50
- Sex: more males than females develop myeloma
- Race: People who have non-Hispanic black heritage have more than twice the age-adjusted incidence rate of myeloma than those who have non-Hispanic white heritage
- Family risk/germline predisposition: having a parent or sibling with myeloma
- Medical history: people with a history of MGUS (monoclonal gammopathy of unknown significance) are at higher risk
- Environment: studies are investigating a link between the development of myeloma and exposure to radiation; certain chemicals, such as pesticides, fertilizer, and Agent Orange, and certain metals, such as cadmium, antimony, and lead
- Occupation: studies indicate that firefighters have a statistically significant higher risk for multiple types of cancer than the general population
Plasmacytomas
Malignant plasma cells are most commonly found in bone marrow, but they may accumulate in any part of the body. This is known as a “plasmacytoma.” If the malignant cells form only a single tumor, it is called a “solitary plasmacytoma.” A plasmacytoma can often be cured with radiation therapy alone, but it may recur or later develop into multiple myeloma.
Precursors to myeloma
Before developing active myeloma (myeloma that causes symptoms), patients pass through two earlier stages: monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma. These two pre-cancerous plasma cell disorders may develop into active myeloma.
- Monoclonal gammopathy of uncertain significance (MGUS): This is a condition in which there is a higher-than-normal level of M protein in the blood. MGUS does not cause any symptoms. Patients with MGUS are usually monitored with blood tests once or twice a year. Only 20 percent of people diagnosed with MGUS eventually develop myeloma.
- Smoldering myeloma: This is the stage between MGUS and active myeloma. People with smoldering myeloma usually have no symptoms but need to be checked often for signs of progression to active myeloma.
You should be treated by a hematologist-oncologist, a specialist who treats people with myeloma or other types of blood cancer.
Treatment outcomes vary widely among patients; results depend on many individual factors.
Related diseases
Myeloma shares some similar features and symptoms with other blood disorders, including the following:
This is a group of conditions that cause kidney damage. The damage is caused by plasma cells or B cells that make M proteins that can build up in the kidneys and damage them. MGRS is not cancer and not active myeloma. However, it does require treatment to help kidney function. A bone marrow and kidney biopsy are needed for diagnosis. Typically, treatment for MGRS is similar to treatment for active myeloma.
This disease has some features in common with myeloma. It is a malignancy of B lymphocytes that produce a monoclonal immunoglobulin that can be measured in the blood. The malignant B lymphocytes replace the normal marrow cells and may cause anemia and other blood cell deficiencies by preventing the normal marrow cells from making blood cells efficiently. The monoclonal (M) immunoglobulin, produced by the malignant B lymphocyte, is a very large type of immunoglobulin M (IgM), referred to as a “macroglobulin” (large globulin).
Learn more about WM in our free fact sheet, Waldenström Macroglobulinemia Facts.
AL amyloidosis (amyloid light chain or primary amyloidosis) involves clumps of the light chain produced by myeloma cells that are called amyloid fibrils and can deposit in organs. Symptoms include nerve damage, kidney damage or heart damage. AL amyloidosis can occur in patients who also have active multiple myeloma, but it is more often diagnosed in patients who otherwise only have MGUS or smoldering myeloma. In other words, AL amyloidosis is often diagnosed because the proteins (light chain clumps called amyloid fibrils) are causing symptoms, not because the cells (pre-cancerous myeloma cells that are not themselves causing bone damage) are causing symptoms.
Many of the drugs that work against myeloma are also effective against amyloidosis, including corticosteroids, melphalan, bortezomib and daratumumab. In contrast, lenalidomide should be used with caution particularly in patients who have heart issues (shortness of breath) or gut issues (constipation) related to their underlying amyloidosis.
The goal of amyloidosis treatment is to normalize the light chains to prevent any further amyloid fibril (clump) deposition in the organs; after that, the body can slowly clear out the clumps on its own. For patients whose light chains normalize with treatment, autologous stem cell transplantation can be considered but is no longer required (unlike in multiple myeloma, where it is generally still recommended).
Learn more about AL amyloidosis in our free fact sheet, Amyloidosis.
This is a rare plasma cell disease that may be primary (without known cause) or secondary (evolving from an existing diagnosis of myeloma). Most cases are primary; only about 5 percent of cases are diagnosed in patients who have myeloma. In this disorder, patients have a high level of plasma cells (greater than 20 percent) circulating in the blood, often creating plasmacytomas throughout the body. This disease is treated like myeloma. However, patients frequently require more aggressive therapy because PCL is more aggressive than myeloma.
POEMS syndrome is an uncommon marrow disorder related to myeloma. It gets its name from its five most common features:
- Peripheral neuropathy
- Organ enlargement
- Endocrine gland dysfunction
- Monoclonal plasma cell tumors and monoclonal immunoglobulin
- Skin changes
Peripheral neuropathy is often the most disabling feature of the syndrome and can include progressive weakness of the arms or legs. Liver or spleen enlargement is less common. The bone alterations related to the accumulation of plasma cells in the marrow are different from bone alterations in classic myeloma (the marrow looks denser than normal, rather than less dense). Thyroid or sex hormone deficiencies caused by endocrine gland dysfunction may require hormone replacement therapy.
Other features not included in the POEMS acronym are high red blood cell or platelet counts, extravascular volume overload (swelling), and lung disease. Patients can benefit from radiation or chemotherapy treatment and, in some cases, from autologous stem cell transplantation.
Find facts and statistics for myeloma and other blood cancers.
Find more information on myeloma in the National Comprehensive Cancer Network (NCCN) Guidelines for Patients.
Source: Myeloma. Reviewed by Rahul Banerjee, MD, FACP.
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