Myeloma is a rare blood cancer that begins in plasma cells, a type of white blood cell normally responsible for producing antibodies that help fight off infectious pathogens and other threats.
When these cells become cancerous, they grow out of control in the bone marrow, the spongy tissue inside some bones where blood cells are generated. Called myeloma cells, these abnormal cells also produce large amounts of an abnormal antibody, called M protein, which causes a number of complications.
Because most myeloma patients have myeloma masses in more than one bone marrow location, the disease is often called multiple myeloma.
The exact cause of most myeloma cases remains unclear, but scientists believe that genetic changes make plasma cells turn cancerous. These genetic abnormalities differ from patient to patient, and while some have been identified as genetic risk factors, the disease is not thought to be inherited.
Similar to other cancers, mutations in oncogenes and tumor suppressor genes have been identified in myeloma cells. Oncogenes promote cell growth, while tumor-suppressing genes are responsible for controlling cell growth and triggering cell death. Duplications and deletions of genetic material, as well as abnormal exchanges between chromosomes — called translocations — may either turn on oncogenes or turn off tumor-suppressing genes, making cells divide uncontrollably and thus allowing them to survive beyond their normal lifespan.
Several non-genetic factors also have been associated with an increased risk of developing myeloma. These include older age, being male, Black race, having a history of myeloma or other plasma cell-related conditions in the family, obesity, and exposure to high levels of radiation or to certain chemicals, pesticides, and herbicides.
Myeloma signs and symptoms can be diverse and, in the early stages of the disease, they may not be noticeable or may appear unrelated to each other.
The most common symptoms include bone pain and fragility, reduced blood cell numbers, and kidney damage. Notably, reduced blood cell numbers can result in weakness/fatigue, abnormal paleness, excessive bleeding and/or bruising, and recurrent infections.
People with myeloma also may experience increased thirst and urination, lack of appetite, nausea, and constipation. These symptoms often are due to abnormally high levels of calcium in the blood, a condition called hypercalcemia. The weakened bones in myeloma patients also may lead to spinal cord compression and nerve damage that result in sudden, severe back pain, muscle weakness, and numbness sensations, as well as bladder and bowel problems.
The diagnosis of myeloma typically requires a clinical assessment, a detailed patient history, and a variety of specialized laboratory, bone marrow, and imaging tests.
Such tests include the removal and evaluation of small samples of bone marrow — a biopsy or aspiration —and blood tests to examine blood cell counts, calcium levels, and kidney function. Various imaging scans of the bone, including magnetic resonance imaging, computed tomography, and positron emission tomography, also may be done to further the diagnosis.
Blood and urine tests also can be used to measure the levels of the abnormal M protein produced by myeloma cells, as well as a small fragment of that protein — called light chain when in the blood and Bence Jones protein when detected in the urine.
The criteria for a positive myeloma diagnosis include the biopsy-proven presence of myeloma tumors or at least 10% of plasma cells in the bone marrow, and one or more specific parameters. These include higher-than-normal blood calcium levels; impaired kidney function; anemia, or low red blood cell counts; bone lesions on imaging tests; excessive levels of one type of light chain (a natural fragment of antibodies); and 60% or more plasma cells in the bone marrow.
While there currently is no cure for myeloma, a variety of treatments are available to help control this cancer and relieve its symptoms. The most common therapeutic approaches include an autologous stem cell transplant, immunomodulatory treatments, proteasome inhibitors, CD38 inhibitors, and steroids (which suppress the immune system). Treatment of myeloma typically involves a combination of several types of treatment.
Autologous stem cell transplantation
Autologous stem cell transplant is a standard treatment for myeloma that involves the collection of blood stem cells from the patient’s bone marrow. After a course of high-dose chemotherapy to destroy the myeloma cells, the stem cells are introduced back into the patient to repopulate the bone marrow and produce new, healthy blood cells, including plasma cells. Because this approach involves high doses of chemotherapy, it is very invasive and only recommended for patients who are in good overall health.
One of the most commonly used therapies for myeloma is immunomodulatory medication. These medicines work through several mechanisms, including the suppression of myeloma cell growth and/or by boosting the immune system’s responses against cancer.
Proteasomes are protein complexes that are responsible for breaking down and recycling old proteins. Because cancer cells divide so quickly and produce so much protein, proteasomes have to work overtime to keep the cell functioning. By blocking protein breakdown, proteasome inhibitors promote the buildup of toxic waste proteins, which cause the cells to die.
CD38 inhibitors are antibodies that that targets a protein called CD38, which is primarily found on the surface of myeloma cells. By binding to CD38 on myeloma cells, these antibodies block the cells’ growth and induce their death.
Treatments also may be used to manage symptoms, such delaying bone lesions, easing pain, restoring red blood cells, and helping prevent and fight infections.
A number of experimental therapies also are currently being tested as potential treatments for myeloma.
Last updated: Dec. 5, 2021, by Marta Figueiredo PhD
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