Multiple Myeloma (MM)
What is Multiple Myeloma?
Multiple myeloma, also known as myeloma or Kahler's disease, is a type of blood cancer that affects specific white blood cells called plasma cells. It’s a DNA modification that happens during development in the bone marrow, leading to rapid and uncontrolled cell multiplication.
The build-up of myeloma cells in the bone marrow prevents normal blood cells from being produced leading to the release of only one type of antibody, known as paraprotein or M-protein, which has no valuable immune function.
Multiple myeloma accounted for approximately 34,470 US new myeloma cases in 2022, comprising 1.8% of all newly diagnosed cancer cases. According to the latest available cancer statistics from the "Surveillance, Epidemiology, and End Results (SEER)" program, there were an estimated 159,787 people living with myeloma in the U.S. in 2019.
Myeloma is most frequently diagnosed in individuals who are 65–74 years old, but it can also be diagnosed in people younger than 50. Only 5%–10% of myeloma patients are under the age of 40. Myeloma in children is extremely rare. Men are more likely than women to develop myeloma.
What are the types of Multiple Myeloma?
There are two types of Multiple Myeloma:
- Active Symptomatic myeloma form: a form of myeloma wherein the patient exhibits various clinical symptoms.
- Smoldering myeloma, also called asymptomatic myeloma form: It’s an early stage of myeloma, where the patient doesn’t present clinical symptoms. It usually progresses to active multiple myeloma but may take some time to do so. The risk of progression to active myeloma is 10% per year for the first five years, decreasing in subsequent years.
What are the symptoms of Multiple Myeloma?
There are several physical symptoms associated with multiple myeloma, but these are the most common ones.
Pain
Patients with MM may suffer from pain at different stages of their disease.
Bone pain could be related to osteoporosis, bone lesions, pathologic fractures, and/or vertebral compression fractures, which are common painful occurrences at diagnosis and throughout the course of the disease.
Neuropathic pain can also be caused by monoclonal protein's effect on nerve tissue.
Anemia
The reduction in the number of red blood cells, which carry oxygen throughout the body, results in anemia. This can cause fatigue, weakness, or shortness of breath, and can result either from myeloma or as a side-effect of treatment. The mechanism of anemia in myeloma is not fully understood.
Recurring infection
Multiple Myeloma patients have a greater risk of infection, as their immune system does not function properly, and their white blood cell count is lower than normal.
Unexplained bruising
Due to a low count of blood platelets, MM patients may experience a higher risk of bleeding.
Gastrointestinal symptoms
Calcium can be released into the blood as bone is broken down, resulting in the blood calcium level to be higher than normal. This can cause thirst, nausea, vomiting, confusion, or constipation.
Blurred vision, dizziness, or headaches
Source : Multiple Myeloma Symptoms
How is Multiple Myeloma diagnosed?
Smoldering myeloma does not normally cause symptoms, so it is often diagnosed by chance. The main clinical exams that reveal the disease are:
- Blood test: Blood tests may show an increased level of overall protein, prompting further investigation. These tests focus on measuring the level of blood cells and the amount of abnormal protein (paraprotein) and other substances in blood and/or urine.
- Imaging techniques: X-rays can show loss or thinning of bone (osteoporosis), holes in bone (lytic lesions in bones) or fractures. However, they lack the sensitivity to show the difference between recent and older bone damage, such as active versus inactive myeloma sites.
There are more sophisticated techniques like CT (Computerized Tomography) or MRI (Magnetic Resonance Imaging) scans that are more precise than X-rays, creating a three-dimensional digital image. - Bone marrow aspiration, biopsy and fluorescence in situ hybridization (FISH) tests: Theses procedures involves taking a sample of the liquid part of your bone marrow.
How to treat Multiple Myeloma?
Myeloma treatment is designed to stop or slow the growth of cancer, keeping the disease in remission for as long as possible, and helping patients live better, longer lives.
It is important to talk to your doctor about all your treatment options, including your goals and possible side effects, so that you can choose the best one for you. The specific treatment you choose will depend on several factors, including your age and overall health.
Younger patients who are relatively healthy may be offered higher doses of medication, followed by intensive chemotherapy to kill the abnormal plasma cells and a stem cell transplant to replenish healthy stem cells.
Some people over the age of 70, or those who are unable to tolerate the side effects of intensive treatments, may be given a combination of medications but no chemotherapy or stem cell transplant.
Drug therapies
Combined drug therapy has been found to be more effective than single drugs therapies. A typical combination includes:
- Chemotherapy to kill the myeloma cells (e.g.cyclophosphamide, melphalan or doxorubicin),
- Corticosteroids to suppress inflammation (e.g.dexamethasone or prednisolone),
- Immunomodulatory drugs (IMiDs) to adjust immune responses (e.g.thalidomide, lenalidomide (LEN) and pomalidomide (POM)).
Biological therapies
- Proteasome inhibitors stop and control cell division of myeloma cells. They appear to affect tumor cells more than normal cells, but they are not without side effects (e.g.bortezomib).
- Monoclonal antibodies (mAbs) target neoplastic cells and activate the immune system or disrupt a signaling pathway protecting neoplastic cells from immune-cell destruction (e.g.Elotuzumab).
- Bispecific antibodies (BiAbs) are mAbs simultaneously targeting a tumor-associated antigen and an immune cell-associated antigen to redirect the immune cell cytotoxicity against the tumor cell (e.g., talquetamab).
- CAR T cells Chimeric antigen receptor (CAR) T-cell therapy is to reprogram immune system by extracting T cells, genetically modifying them in vivo, and then reinfusing them back into the body. (e.g., idecabtagene vicleucel).
Transplantation
In a stem cell transplant, the patient receives high-dose chemotherapy to kill the cells in the bone marrow. Then the patient receives new, healthy blood-forming stem cells. When stem cell transplants were first developed, the new stem cells came from bone marrow, and so this was known as a bone marrow transplant. Now, stem cells are more often collected from blood (a peripheral blood stem cell transplant). Transplantation is commonly used to treat multiple myeloma.
Local therapies (Surgery, Radiation)
There is a tendency for these treatments to be helpful for early stage (less advanced) cancers; they are often used in the treatment of solitary plasmacytomas but are less commonly used in the treatment of multiple myeloma.
What are the complications of Multiple Myeloma?
Renal failure: 60 to 70% of patients affected by myeloma experience renal complications. The paraprotein or M-protein found in great quantities in the bloodstream tends to accumulate in kidneys, disrupting their normal function.
Therefore, the prevention of acute kidney failure is essential. This means avoiding dehydration and medication that can cause it (ex. non-steroidal anti-inflammatory drugs such as ibuprofen and ketoprofen, or iodinated contrast agents used for some medical imaging exams).
Heart and Lung Complications: Cardiovascular problems and lung complications are serious and potentially life-threatening conditions that may affect multiple myeloma patients. Many multiple myeloma patients already have conditions such as high blood pressure, high cholesterol, or diabetes. These conditions expose them to venous thromboembolism (VTE) risk and cardiovascular problems.
Finally, the presence of multiple myeloma increases the risk of developing certain cancers such as colon cancer and breast cancer.
How to follow-up after treatment for Multiple Myeloma?
People who have received treatment for multiple myeloma are followed closely by medical professionals. This lifelong follow-up is necessary because multiple myeloma is a chronic disease that is characterized by regular relapses that require treatment.
The follow-up consists of an appointment during which a physical examination and a blood test are performed. X-rays are also ordered. The schedule of these follow-up appointments depends on the patient's individual characteristics and treatment plan.
What signs should patients look out for after treatment for multiple myeloma?
People who have received treatment for multiple myeloma should contact their doctor immediately if they experience any of the following symptoms:
- Bone or back pain,
- Loss of sensation in the feet or hands,
- Mobility problems,
- Unexplained fever,
- Nausea or vomiting,
- Abnormally low or high urine output,
- Fatigue and/or shortness of breath,
- Frequent respiratory, urinary, or other infections,
- Bruising or bleeding.
Sources :
Myeloma-Patients-Guide.pdf (mpeurope.org)
Treating Multiple Myeloma | Ways to Treat Multiple Myeloma | American Cancer Society
Myeloma Statistics | American Cancer Society - Cancer Facts & Statistics
Après le traitement d'un myélome multiple - VIDAL
Multiple Myeloma Pain | International Myeloma Foundation
Published Oct 25, 2023
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