Multiple Myeloma

What is multiple myeloma?

Multiple Myeloma is a cancer that forms in a type of white blood cell called a plasma cell. Healthy plasma cells help fight infections by making antibodies (which are special proteins) that recognize and attack germs.[1]

In multiple myeloma, cancerous plasma cells accumulate in the bone marrow, preventing normal, healthy blood cells from being produced. Instead of producing helpful antibodies, these cancer cells produce an abnormal protein, called monoclonal protein (pronounced MAH-noh-KLOH-nul PROH-teen) or M protein, that can cause complications. In some people, the cancerous plasma cells only produce a part of the abnormal protein. This is called ‘free light chain’.[2, 3]

Signs and Symptoms

The signs and symptoms of multiple myeloma can vary greatly, person by person. The most common symptoms of the disease include:

• Bone pain, especially in your spine or chest 
• Nausea
• Constipation 
• Loss of appetite
• Mental fogginess or confusion
• Fatigue 
• Frequent infections
• Weight loss
• Weakness or numbness in your legs
• Excessive thirst

What are the risk factors for multiple myeloma?

While the exact cause of myeloma is not known, the following factors are recognized to be associated with an increased risk of developing the disease.[4, 5]

• Increasing age: Your risk of developing multiple myeloma increases as you age, with most people being diagnosed in their mid-60s. 
• Male gender: Men are more likely to develop the disease than women.
• Family history: People with a parent, sibling, or child who has myeloma are up to twice as likely to develop the disease compared to those who do not have a family history.
• Race & ethnicity: Black people or people of African origin are more likely to develop multiple myeloma than white or Asian people. One possible reason for this is that people of African origin have a higher chance of developing a blood disorder called monoclonal gammopathy of undetermined significance (or MGUS). 

MGUS is a condition in which the body makes M protein (an abnormal protein) within the bone marrow, which is the soft, blood-producing tissue that fills the center of most of our bones. MGUS occurs most commonly in older men, and while it usually causes no problems, it can lead to more serious diseases, like multiple myeloma. People who have MGUS should get regular checkups so they can get earlier treatment if the condition progresses.

It is important to highlight that not everyone who has MGUS develops multiple myeloma but everyone with multiple myeloma has had MGUS before they got cancer.

Types of myeloma

As previously noted, the first stage of myeloma is a benign condition called monoclonal gammopathy of undetermined significance (or MGUS). At this stage, there is a low level of M protein in the blood and it does not cause any symptoms or problems for the person. In fact, most people with MGUS are unaware that they even have the condition. Only 20 percent of people diagnosed with MGUS eventually get multiple myeloma over the course of their entire life.[9]

Smoldering multiple myeloma (SMM) is an intermediate state between MGUS and multiple myeloma.[10] Like MGUS, SMM does not have any symptoms and is usually diagnosed by the doctor during routine check-ups. However, unlike MGUS, people with SMM have up to 60 percent abnormal bone marrow plasma cells compared to people with MGUS who have a maximum of 10 percent abnormal cells. The amount of M protein in people with SMM is also higher than in those with MGUS.[11]

Multiple myeloma is the final stage of myeloma that is diagnosed by having both abnormal bone marrow plasma cells and active indicators of the disease (which means the multiple myeloma is causing damage to the person’s body). These indicators may include an increase of calcium in the blood (also called hypercalcemia), kidney damage (where the kidneys are less able to filter and purify the blood), low red blood cell count (also known as anemia), and/or bone damage.[12]

What are the complications of multiple myeloma? [13]

• Frequent infections: Multiple myeloma reduces the body’s ability to fight infections. This is because instead of producing healthy cells that can help the immune system, the bone marrow of a multiple myeloma patient produces cancerous cells.
• Anemia: Most people with multiple myeloma have anemia, a condition in which the body does not produce enough healthy red blood cells to carry adequate oxygen throughout the body. This happens because the bone marrow of a multiple myeloma patient produces cancer cells, which “crowd out” the healthy red blood cells that are being produced. This can leave a person feeling weak and tired. 
• Bone damage: Multiple myeloma can also damage or weaken the bones, leading to bone pain, broken bones, and osteoporosis, a condition that results in brittle and thin bones. This happens when rapidly growing myeloma cells form growths or masses in the bone marrow, causing physical damage to the bone. Myeloma cancer cells also create substances that harm the body’s ability to grow new bone, slowing down the possibility to fix damaged bones.
• Hypercalcemia: Bone damage resulting from multiple myeloma can lead to hypercalcemia, a condition in which the calcium level in the blood is higher than normal. This happens because when bones are damaged, calcium leaks from the bones into the bloodstream. High levels of calcium in the blood can lead to a coma or heart attack. 
• Kidney problems: About half of the people with multiple myeloma have kidney damage. If you have kidney damage, you may notice a drop in how much urine you make. Your blood work may show high levels of creatinine, a protein that healthy kidneys usually filter out.
• Heart and lung problems: Multiple myeloma also puts you at risk of developing heart and lung problems, such as blood clots, pulmonary hypertension, heart failure, and irregular heartbeat. A person’s risk of developing these problems is greater if you already have high blood pressure, type 2 diabetes, or high cholesterol.

How is multiple myeloma diagnosed?

Multiple myeloma is often diagnosed when your doctor detects it accidentally during a routine blood test or test for another condition. It can also be diagnosed if your doctor suspects you could have multiple myeloma based on your signs and symptoms.

Tests and procedures used to diagnose multiple myeloma include:

• Blood tests: Laboratory analysis of your blood may reveal the M proteins produced by myeloma cells, as well as the presence of abnormal free light chains (a part of the M protein). Approximately 20 percent of people diagnosed with multiple myeloma, do not have any signs of M proteins in their blood, which means that free light chains are the only detectable product of their cancerous plasma cells. Additionally, blood tests to examine your kidney function, blood cell counts, calcium levels and uric acid levels can give your doctor even more clues about your diagnosis.
• Urine tests: Analysis of your urine may show M proteins, also known as Bence Jones proteins when they're detected in urine. The amount of protein in the urine is a good way for doctors to understand just how much protein is being leaked by the kidneys as a result of damage caused by multiple myeloma.
• Examination of your bone marrow: Your doctor may remove a sample of bone marrow for laboratory testing. The sample is collected with a long needle inserted into a bone in the pelvis (known as a bone marrow aspiration and biopsy). In the lab, the sample is examined for myeloma cells. Specialized tests, such as fluorescence in situ hybridization (FISH) can analyze myeloma cells to identify genetic mutations. Bone marrow samples can also be taken to assess the remission (decrease in or disappearance of signs and symptoms) of the disease after treatment, which may not be measured by standard tests. These samples are analyzed using specialized tests to detect any remaining small amounts of myeloma cells, also known as Minimal Residual Disease (MRD). For more information about MRD testing, please see a brief video here.

• Imaging tests: Imaging tests may be recommended to detect bone problems (such as fractures, holes in the bones, reduced bone density) associated with multiple myeloma. Tests may include an X-ray, magnetic resonance imaging (MRI), computerized tomography (CT) scan, or positron emission tomography (PET). Imaging is also important to detect if the bone marrow cells are growing outside the bones (pushing on a nerve and causing pain) or if there are lumps of myeloma cells growing on their own in other parts of the body other than the bone.

What are the treatment options for multiple myeloma?[14, 15, 16, 17, 18, 19]

There are many different options for the treatment of multiple myeloma. The medication or combination of medications used by your physician depends on many factors, including your:

• Age, 
• Overall health,
• Overall physical condition,
• Medicines you may have used previously,
• Whether you are a candidate for a stem cell transplant, and
• How aggressive your disease is.

Currently, treatments for multiple myeloma include:

• Stem cell transplant (also called a bone marrow transplant): Is a procedure where healthy blood-forming cells (called stem cells) are collected and reintroduced to a patient’s bloodstream after cancer treatments like chemotherapy have been given.

A stem cell transplant is usually given after a few cycles of chemotherapy (called induction therapy), which are used to kill as many abnormal cancer cells in the body as possible. Before a patient goes through induction therapy, their stem cells are collected from their blood using a machine that is similar to a kidney dialysis machine. Patients then go through another round of treatment with high-dose chemotherapy to kill any cancer cells that may have remained in the body after induction therapy. This process is very effective at killing abnormal cancer cells, but it also causes significant damage to healthy cells in the bone marrow and elsewhere in the body. Once a patient completes the induction therapy period, their previously collected stem cells are then infused back into the body (through a process that is similar to a blood transfusion) where they move to the bone and begin rebuilding the bone marrow to help the body speed up the recovery of its healthy tissue. The process of using a patient’s own stem cells for a transplant is called an autologous transplant. This type of transplant is a standard treatment for multiple myeloma, and although it can make the disease go away for a while (a period called remission), it is not a cure for multiple myeloma.[20, 21, 22]

In rare cases, some patients are offered a different type of stem cell transplant called an allogeneic transplant where the patient gets stem cells from a donor, usually a close relative like a brother or sister. In this approach, the stem cells are collected either from the donor’s blood, from the bone marrow within a donor’s hipbone, or from the blood of a donated umbilical cord. Before going through an allogeneic stem cell transplant, the patient receives immunosuppressive therapy or radiation (called a conditioning period) to prepare the acceptance of the donor stem cells. The donor stem cells expand and generate a new immune system replacing the one of the patient; this new immune system is responsible to detect and kill the myeloma cells. The type of treatment a patient undergoes during the conditioning period depends on their disease and their individual case. Allogeneic transplants are riskier than autologous transplants and are currently not considered a standard treatment for multiple myeloma.[23, 24]

• Chemotherapy: Are medicines that use powerful chemicals to kill all fast-growing cells, such as cancer cells, in the body.
• Immunotherapy drugs: Are a type of medicine that boosts the body’s immune system to fight cancer. They use substances made by the body or in a laboratory to improve how the immune system works to find and destroy cancer cells.[25] Monoclonal antibodies are one example of immunotherapy drugs.
• Radiation therapy: Uses high-powered energy beams from sources, such as X-rays to kill cancer cells. Radiation therapy may be used to shrink myeloma cells in a specific area like on a tumor that’s causing pain or destroying the bone.[26]
• Proteasome inhibitors: Are a type of medicine that blocks the ability of myeloma cells to appropriately function, leading to their own cell death.[27]
• Immunomodulatory drugs: Are medicines that increase the body’s own immune system’s ability to recognize and kill myeloma cells.[28, 29, 30, 31]
• Corticosteroids: Are medicines that regulate the immune system to control inflammation in the body. They are usually given in combination with other medicines, such as immunotherapy, immunomodulatory drugs, or chemotherapy as they have some anticancer effects, and can help manage side effects from other medicines.[32, 33]