Multiple Myeloma

Multiple myeloma is a type of blood cancer that forms in the plasma cells, or white blood cells in the bone marrow. Plasma cells normally produce antibodies, which are blood proteins the immune system uses to fight off harmful bacteria and viruses. The plasma cells in people with multiple myeloma grow out of control and limit the growth of healthy cells. If untreated, cancer cells can damage the kidneys, bones, and immune system, and cause anemia.

Many people with multiple myeloma may not notice symptoms. Multiple myeloma typically goes unnoticed until a healthcare provider discovers it during a routine blood test. People with the condition may sometimes have bone pain and fatigue.

A diagnosis of multiple myeloma can be scary and unsettling. An early diagnosis helps you get treatment in the early stages, reduce symptoms, slow disease progression, and prolong survival. The five-year relative survival rate is nearly 60%.

Multiple myeloma is rare, representing less than 2% of all cancer diagnoses in the United States. About 159,800 people have the condition. Read on to learn about multiple myeloma symptoms, stages, treatments, and more.

Types

Each type of multiple myeloma differs depending on what form of abnormal antibodies they produce. A healthcare provider may classify multiple myeloma into one of several types: typical, Bence Jones, non-secretory, or immunoglobulin gamma (IgM).

Typical Myeloma

Typical myeloma is the most common form of multiple myeloma. People with typical myeloma may have plasma cells that produce one of the following antibodies:

• IgA kappa or epsilon
• IgD
• IgE
• IgG kappa or epsilon 
• IgM
  

Bence Jones Myeloma

Bence Jones myeloma, also referred to as light chain myeloma, affects 15% to 20% of people with multiple myeloma. People with Bence Jones myeloma have cancerous plasma cells that produce proteins called kappa or epsilon. Kappa and epsilon proteins may damage the kidneys and nerve cells.

Non-Secretory Myeloma

People with non-secretory myeloma may produce little or no abnormal antibodies. Non-secretory myeloma is rare and generally only affects 1% to 5% of people with multiple myeloma.

Immunoglobulin Mu (IgM) Myeloma

People with IgM myeloma, also called Waldenström's disease, produce too many IgM antibodies. This type of myeloma is rare, affecting less than 1% of people with multiple myeloma.

The development and treatment of IgM myeloma are different from other types of multiple myeloma. IgM myeloma may cause damage to your lymph nodes, so the disease is classified as a plasmacytic lymphoma.

Multiple Myeloma Symptoms

The majority of people may not notice symptoms before receiving a diagnosis. You may begin to have multiple myeloma symptoms as the disease progresses, such as:

• Bone loss and fractures: Bone loss may happen if cancerous cells spread to the bone. If they metastasize (spread), cancer cells can form tumors and lytic lesions (a type of bone destruction) in the bones. Bone loss and destruction can increase fracture risk.
• Bone pain: This type of pain mainly occurs during an advanced stage of cancer. You may feel bone pain in your chest, arms, and legs. Moving your body too much can worsen bone pain.
• Bruising: If cancer cells build up underneath the skin, you may start to notice bruise-like bumps on your body.
• Frequent infections: Plasma cells are essential for proper immune system function. Multiple myeloma may weaken the immune system when plasma cells become cancerous. A weak immune system makes it hard for the body to fight off infections, making you more vulnerable to bacteria and viruses.
• Neurological damage: Multiple myeloma may cause fractures in the spine, which can damage nerve cells. Damaged nerve cells can result in neurological symptoms like numbness, tingling, pain, or muscle weakness. Loss of bowel or bladder control may also occur. 

Causes

Multiple myeloma affects the plasma cells, a type of white blood cell. These cells aid in the body's immune response. Bone marrow, or the soft tissue inside many bones, creates white blood cells. Abnormalities in the plasma cells grow out of control and can form tumors in people with multiple myeloma.

The exact cause of multiple myeloma is unknown, but experts believe that genetic changes play a role. People with the condition often have somatic mutations that affect genes that control cell division. Somatic mutations are genetic changes that aren't passed down from generation to generation. These changes instead develop over the course of a person's life.

Risk Factors

Some evidence suggests factors that can increase the likelihood of multiple myeloma include:

• A family history of the condition
• Being older than 65
• Exposure to radiation or harmful chemicals, such as herbicides or insecticides
• Infections
• Other conditions that also affect the plasma cells
  

Diagnosis

A healthcare provider or oncologist (who specializes in cancer) can diagnose multiple myeloma. They'll likely ask questions about your health history and symptoms. The "CRAB" criteria may indicate multiple myeloma.

CRAB is an acronym for:

• Calcium (higher than usual in the blood)
• Renal (liver) failure
• Anemia
• Bone disease

Not everyone with multiple myeloma has all of these issues at the time of diagnosis. Routine blood tests are one of the first signs the body is producing abnormal antibodies. A healthcare provider may further analyze blood samples or order additional tests if they suspect multiple myeloma.

Other diagnostic tests can include:

• Biopsy: A healthcare provider can take a sample of skin tissue to confirm multiple myeloma.
• Bone aspiration: This test involves removing a sample of bone marrow.
• Imaging tests: A healthcare provider may use imaging tests like an X-ray, MRI, or CT scan to determine if the cancer has spread and where. Bone loss may also be noticeable on X-rays.
• Urine tests: Abnormal proteins can also show up in a urine sample.

Stages of Multiple Myeloma

A healthcare provider will evaluate your blood tests, imaging tests, or bone or skin tissue to stage multiple myeloma. Stages include:

• Stage 1: This is also known as monoclonal gammopathy of undetermined significance (MGUS). Blood tests may show less than 3 grams (g) of abnormal antibodies per deciliter (dl) of blood. People with MGUS don't typically have symptoms. You may not meet the "CRAB" criteria or have any damage to your organs.
• Stage 2: This is also known as smoldering myeloma. Blood tests yield more than 3 g of abnormal antibodies per dl of blood. People with smoldering myeloma may not have symptoms or meet the "CRAB" criteria. About 50% of people in this stage will develop multiple myeloma within five years.
• Stage 3: This happens when smoldering myeloma progresses into multiple myeloma. People in stage 3 will have more than 3 g of abnormal antibodies per dl of blood. You may meet one or more of the "CRAB" criteria and have organ or tissue damage.
  

Multiple Myeloma Treatment

There is no cure for multiple myeloma. Treatments can slow disease progression, manage symptoms, and improve the quality of life.

Multiple myeloma typically progresses slowly. You might not need treatment right away if you are in stage 1 or stage 2. A healthcare provider may monitor disease progression closely by setting up check-ins and blood tests every three months.

People in stage 3 may require immediate treatment. Many different treatment options are available. A healthcare provider, oncologist, and any other specialist on your care team will conduct tests to determine the type of multiple myeloma you have.

A combination of treatments can be helpful in targeting multiple myeloma and reducing symptoms:

• CAR-T therapy: This is a type of immunotherapy. CAR-T therapy uses genetically-modified cells to target and attack cancer cells. 
• Chemotherapy: This drug treatment aims to kill fast-growing cancer cells. Chemotherapy may control or stop the progression of multiple myeloma in some people. 
• Corticosteroids: Some corticosteroids, like prednisone, can be combined with chemotherapy treatment to improve symptoms. These are generally available in pill form.
• Immunomodulators: These medicines help the immune system target and destroy cancer cells.
• Monoclonal antibodies: These proteins target antigens on cancer cells. Antigens are substances that help produce abnormal antibodies. 
• Nuclear export inhibitor: The nuclear export transfers proteins out of the nucleus in cells. The nucleus of a cell contains the genetic material that produces harmful proteins. Inhibitors can prevent protein build-up and kill cancer cells.
• Proteasome inhibitors: People with multiple myeloma have an abnormal amount of antibodies. Proteasome breaks down these antibodies in the cells and causes them to spread. Using a proteasome inhibitor can prevent the spread of cancer cells.
• Stem cell transplantation: A healthcare provider may use your or a donor's bone marrow stem cells for a transplant. Transplants do not cure multiple myeloma but can slow disease progression. 
  

Prevention

There are no known therapies that can stop MGUS or smoldering myeloma from progressing into multiple myeloma. Research has found preliminary evidence that preventing infections can slow the progression of multiple myeloma. Infections are currently one of the primary risk factors for developing the condition.

The following actions can prevent infections:

• Being vaccinated against common bacteria and viruses
• Receiving antimicrobial prophylaxis, which helps prevent infections before surgeries
• Replacing antibodies in people who are at risk of developing the disease 
• Taking infection control measures (e.g., hand hygiene, using personal protective equipment, and disinfecting shared surfaces)

Related Conditions

Multiple myeloma can increase the risk of different conditions. The reason why people with multiple myeloma can develop other conditions is because the cancer cells affect the blood and several organs.

Some of the most common related conditions include:

• Anemia: Fatigue often occurs due to anemia, or when the body doesn't have or make enough red blood cells to carry oxygen throughout the body.
• Hypercalcemia: The bones can release an excess amount of calcium into the blood if they break down. High blood calcium levels, or hypercalcemia, may cause symptoms like nausea and vomiting, frequent urination, and excessive thirst.
• Hyperviscosity syndrome: This condition causes the blood to thicken and makes it difficult for blood to move freely in and around the blood vessels. Hyperviscosity syndrome happens when there are too many proteins in the blood. Symptoms may include bleeding in the nose and mouth and heart failure.
• Kidney damage: Kidney damage or failure is one of the first noticeable complications of multiple myeloma. An abnormal amount of proteins and calcium in the blood may cause damage to the kidneys.
  

Living With Multiple Myeloma

Living with multiple myeloma can be difficult. You may feel sad, frustrated, or hopeless when you receive a diagnosis. These feelings are normal. It can be hard to live with symptoms and go in for treatment.

A team of healthcare providers can help make your condition feel more manageable. Some evidence suggests that partaking in regular light exercise, eating a nutritious diet, and getting enough sleep can ease symptoms.

You may also find it helpful to seek out support from your family, friends, and other people with multiple myeloma to make your condition feel less overwhelming. You may consider asking a healthcare provider for a referral to a mental health specialist if you feel like your diagnosis is weighing on your emotional well-being.