Multiple myeloma emerges when plasma cells, white blood cells that help fight infections, begin to develop abnormally. Those cells crowd out the healthy cells in your bone marrow and form tumors. Over time, they can cause a wide range of symptoms, from calcium build-up and kidney problems to anemia, bone lesions and fractures.
Being diagnosed with multiple myeloma can be challenging, but as you learn more about the disease you’ll find that there are effective treatment options to manage it, with new ones on the way in 2021. While there is no cure for multiple myeloma, scientific advances have led to better treatment options and longer life expectancies, giving myeloma patients and their loved ones a reason to remain hopeful.
Multiple myeloma is more common in men than in women, more common in people of African and African American descent than in people of European/Caucasian descent, and most prevalent in people age 65 years and older.
- What is Multiple Myeloma?
- MM Symptoms
- MM Causes and Risk Factors
- MM Diagnosis
- MM Stages
- MM Treatment
- MM Survival
- Frequently Asked Questions
Multiple myeloma is a cancer of plasma cells, a type of white blood cell found in the bone marrow. Healthy plasma cells create antibodies in response to infections and are an important part of the immune system. When plasma cells become cancerous, they can crowd out normal white blood cells, red blood cells and platelets, all of which are also made in the bone marrow. The disease is called “multiple” because it often affects several areas of the body, and “myeloma” because it affects the bone marrow.
Multiple myeloma does not always cause obvious symptoms, especially early on. When multiple myeloma symptoms do occur, they usually include one or more of the following:
- bone pain — often in the back, hips, shoulders or ribs
- broken bones (fractures)
- frequent infections or infections that don’t go away
- pain or numbness in your toes
Approximately 10% to 15% percent of patients diagnosed with myeloma will have no symptoms at the time of their diagnosis. But even without symptoms, myeloma can be caught on a routine blood test. If your doctor notices that your red blood counts are low or you have elevated protein levels in your blood, they will likely send you for additional testing.
It is not currently understood what causes multiple myeloma. However, according to the Mayo Clinic, the disease almost always begins as a generally benign condition known as monoclonal gammopathy of undetermined significance, or MGUS. In both MGUS and multiple myeloma, the body produces abnormal antibodies called monoclonal proteins or M-proteins. Unlike antibodies produced by healthy plasma cells, the M-proteins produced by myeloma cells can’t help the body fight infections. Instead, they lead to problems with the bones, blood, calcium levels and kidneys.
There are a number of risk factors that have been identified with developing multiple myeloma:
- Gender: Men are more likely than women to develop the disease.
- Race/Ethnicity: According to the Mayo Clinic, Black people are twice as likely as others to develop multiple myeloma.
- Age: Your risk of developing the disease rises as you age. Most multiple myeloma patients are diagnosed in their 60s.
- Weight: Obesity increases your risk of developing multiple myeloma.
- Family History: A family history of the disease will increase your chance of having it, as will a personal history with MGUS.
- Exposure to radiation: Some studies have found that occupational exposure to radiation may be a risk factor, but further research is needed.
It’s difficult to detect multiple myeloma early, especially since symptoms can be subtle and many don’t realize they have it until it has already started to affect the organs. However, those with MGUS should have regular blood tests done to check for disease progression.
This aside, there are tests that are able to detect myeloma. Here are some tests that your doctor might recommend:
Complete Blood Count
A complete blood count (CBC) will measure your red and white blood cells and your blood platelets. Because myeloma cells replace healthy blood cells in bone marrow, low levels can be indicative of myeloma.
Blood Chemistry Tests
Blood chemistry tests check for a number of different components in your blood that can be signs of myeloma. High creatinine and calcium levels in addition to low albumin levels are common in people with the disease. In addition, total protein levels may be elevated due to the excess antibody production from the malignant plasma cells.
Serum Protein Electrophoresis
Serum protein electrophoresis measures antibodies (a type of protein) in your blood. As we normally have different types of immune cells making many different antibodies to fight an array of infections (flu, pneumonia, etc.), this test typically finds a polyclonal pattern; poly meaning many. In myeloma, where there is one group of malignant plasma cells making one bad protein, this test will show a monoclonal pattern; mono meaning one.
Urine Protein Electrophoresis
Urine protein electrophoresis (UPEP) and urine immunofixation (UIFE) are urine tests that check for certain proteins created by myeloma cells that have been filtered through your kidneys. The presence of monoclonal proteins (M-proteins) indicates an immune system disorder, such as multiple myeloma. These tests use a routine urine sample, but you may be asked to collect all of your urine over a 24-hour period.
Bone Marrow Biopsy
A bone marrow biopsy is another way to test for myeloma. There are two parts to the procedure — bone marrow aspiration and biopsy. The procedure itself is an office procedure lasting typically 10-20 minutes. A local anesthetic is injected to numb the skin and covering of the bone called the periosteum. During the biopsy procedure, a small amount of bone marrow tissue will be withdrawn with a needle, (aspiration) and a marrow core (biopsy) will be taken from the hip bone. The sample will then be examined under the microscope to check for myeloma cells.
If you’ve been diagnosed with multiple myeloma, your doctor will likely recommend additional tests to diagnose and determine the presence of genetic mutations. These follow-up tests are important because they can help you and your medical team decide which treatment is right for you.
I’ve Been Diagnosed With Multiple Myeloma, Now What?
Your doctor will help you determine the best immediate course of action. If possible, consult a specialist. With telemedicine, you may even be able to speak to a myeloma expert from the comfort of your own home.
Patients without symptoms may not need to begin treatment for months, years or potentially ever. If you’ve been diagnosed with multiple myeloma but don’t need treatment right away, you can expect your doctor to regularly monitor your condition, likely in the form of routine blood and/or urine tests. Routine radiographic imaging may be needed as well.
Some patients find that joining a multiple myeloma support group helps them process their diagnosis and learn from others who are on a similar journey.
The International Staging System (ISS) and the Revised International Staging System (R-ISS) are the two systems used to determine the stages of multiple myeloma. Here, we use R-ISS. If your doctor uses ISS, the information they provide may differ. Both are correct.
According to the American Cancer Society, there are four factors taken into consideration when staging myeloma:
- the amount of albumin in the blood,
- the amount of beta-2 microglobulin in the blood,
- the amount of LDH in the blood,
- the gene abnormalities (cytogenetics) of the cancer.
The three R-ISS stages of multiple myeloma are as follows:
- Stage I: Serum beta-2 microglobulin is less than 3.5 (mg/L) AND albumin level is 3.5 (g/dL) or greater AND cytogenetics are considered “not high risk”
- Stage II: Not stage I or III
- Stage III: Serum beta-2 microglobulin is 5.5 (mg/L) or greater AND cytogenetics are considered “high-risk” AND LDH levels are high
High-risk cytogenetics is defined as the presence of del(17p) and/or translocation t(4;14) and/or translocation t(14;16).
To learn more about cancer staging, talk to your doctor. He or she can answer your questions and help you better understand your stage and prognosis.
There are numerous myeloma treatment options that can help you continue to live a happy and productive life.
This treatment option uses drugs that focus on specific abnormalities of cancer cells, and interferes with their ability to break down proteins, causing them to die. Targeted therapy drugs used to treat myeloma include:
- Immunomodulating drugs: These drugs boost the immune system while impeding the ability of cancer cells to divide and spread. Examples: lenalidomide (Revlimid), pomalidomide (Pomalyst), and thalidomide (Thalomid).
- Proteasome inhibitors: All cells make garbage. Myeloma cells make lots of garbage (M-spike, M-protein). Proteasome inhibitors block the “garbage disposal system” of the cell. The cell fills up with garbage and explodes or dies. Examples: bortezomib (Velcade), carfilzomib (Kyprolis) and ixazomib (Ninlaro).
- Monoclonal antibodies: These are manufactured versions of a protein (antibodies) made by the immune system to fight infections. Just as healthy immune cells make antibodies to attack bacteria and viruses, these drugs/ antibodies attack cancer cells. Examples: daratumumab (Darzalex), isatuximab (Sarclisa) and elotuzumab (Empliciti).
- Histone deacetylase (HDAC) inhibitors: These drugs target a protein that allows myeloma cells to grow and spread rapidly, and they affect which genes are active inside cells. Example: panobinostat (Farydak).
- Selective inhibitors of Nuclear Export (SINE): Our body has a natural process of killing cancer cells; called apoptosis (programmed cell death). Cancer cells can avoid apoptosis by moving key components/proteins of this pathway outside of the nucleus. SINE compounds prevent the cancer cells from moving these proteins, forcing the cell to follow the body’s signal to kill itself. Example: selinexor (Xpovio).
Chemotherapy uses strong oral and/or intravenous drugs to attack cells that are in the process of dividing. It primarily kills cancer cells, but some healthy cells will be affected too. Chemotherapy drugs used to treat myeloma include cyclophosphamide (Cytoxan), doxorubicin (Adriamycin), bendamustine (Treanda) and melphalan (alkeran).
These drugs help regulate the immune system and are also active in combating myeloma cells. They can be used alone or in combination with other myeloma drugs. Examples: dexamethasone and prednisone.
This treatment uses X-rays to target and attack myeloma cells. The goal of radiation therapy is to damage the cancer cells and stop them from spreading.
Stem Cell Transplant
Also called a bone marrow transplant, this treament is a multi-step process. First, your myeloma specialist will collect healthy stem cells from your blood. Next, they will administer a high dose of chemotherapy, intended to wipe out almost the entire bone marrow. Once this happens, stem cells are then infused into your blood, where they make their way to your bone marrow to begin the production of healthy cells.
There are new multiple myeloma treatments on the horizon, with immune therapies (including CAR-T) likely to be approved in 2021.
Here are a few questions to ask when discussing treatment options with your doctor:
What type of myeloma do I have?
- What stage is the cancer and what does that mean?
- Do I need to start treatment right away?
- Which treatment option/s do you recommend, and why?
- How long will the treatment last?
- What are the risks and side effects?
- How will we know the treatment is working?
- If I don’t need to start treatment immediately, how will you monitor my health? And how often will I see you?
Your treatment plan will depend on your symptoms, overall health and fitness level, results of your blood tests, and your own personal preferences. Talk to your doctor and to a myeloma specialist to get the care that’s right for you.
What Happens If Multiple Myeloma Goes Untreated?
If left untreated, multiple myeloma may not cause many issues at first, as it can be a slow-growing form of cancer. However, if treatment is not begun once symptoms start, the symptoms and the disease will continue to worsen in intensity and will eventually lead to death.
One of the issues most likely to become serious quickly is the health of your kidneys, as higher amounts of myeloma protein can eventually lead to renal damage and even total kidney failure.
While multiple myeloma is not curable, it is treatable. According to Surveillance, Epidemiology, and End Results (SEER) data, published by the National Cancer Institute, the relative five-year survival rate from 2010 to 2016 was 53.9%. This means that approximately 54 of 100 people with myeloma were still alive five years after their diagnosis. Even better, this data also shows that survival rates have steadily increased over the last ten years, meaning the actual five-year estimates may be better than current numbers show.
It’s important to recognize that there is hope — regular medical advancements are making progress.
What Is the M-Spike in Multiple Myeloma?
Because this isn’t produced by healthy plasma cells, M-Spike is often looked for in blood tests as a sign of the disease. Likewise, if M-Spike is found in someone not known to have multiple myeloma, doctors will likely recommend that the patient undergo further testing.
What Is IgG Kappa in Multiple Myeloma?
IgG kappa refers to a specific type of immunoglobulin, or antibody, produced by myeloma cells. These antibodies are made using different types of light chains and heavy chains in their basic structure.
In all of us, there are five different options for heavy chains: IgG, IgA, IgM, IgD, IgE. The “Ig” means immune globulin (protein). We also have two light chain options: kappa and lambda. Plasma cells make antibodies that are typically comprised of one heavy chain and one light chain. IgG kappa antibody is made with an IgG heavy chain and a kappa light chain. As IgG kappa antibody-producing plasma cells are the most common type in the body, they are statistically more likely to become malignant; hence IgG kappa is the most common form of myeloma. When plasma cells only use a light chain to make antibodies, these are called free kappa and free lambda myeloma.
Your doctor will order tests to figure out what kind of multiple myeloma you have, because understanding this nuance will help determine the best treatment plan for you.
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Myeloma occurs most commonly in people over the age of 60. The average age at diagnosis is 70, and only 2% of cases occur in people under 40. However, geriatric oncologists with expertise in hematological malignancies such as multiple myeloma are rare.