Multiple myeloma

Multiple myeloma originates in the plasma cells of the bone marrow. Marrow is the soft, spongy center of most bones that produces new blood cells. These blood cells include:

• White blood cells, which help protect the body against infections
• Red blood cells, which carry oxygen to tissues throughout the body
• Platelets, which help blood form clots to prevent or stop heavy bleeding

A plasma cell (also referred to as a plasma B cell) is a type of white blood cell that creates antibodies, which are special proteins that identify and target germs and help prevent infections. Plasma cells are just one component of the immune system. All told, the immune system is an intricate network of cells, organs, and tissues that work together to defend the body against agents that may cause harm, such as viruses and bacteria.

In multiple myeloma, cancerous plasma cells grow rapidly and accumulate in the bone marrow. These cells eventually crowd out noncancerous cells and disrupt the bone marrow’s ability to produce healthy red blood cells, white blood cells, and platelets. A lack of healthy blood cells in the body can lead to a variety of conditions and complications. These include anemia (in which the body has a low number of red blood cells), frequent infections, heavy bleeding, and other issues.  

Myeloma is the most common type of plasma cell cancer. Because the cancer tends to form in multiple areas of the bone marrow and travel (metastasize) to other parts of the body, it’s often called “multiple” myeloma.

Other types of plasma cell cancer include:

• Solitary plasmacytoma: With this condition, one plasma cell tumor forms in a single part of the body, usually in a bone.  
• Extramedullary plasmacytoma: This involves a plasma cell tumor that forms in a lung, the throat, or another soft tissue.

Overall, multiple myeloma is uncommon. The NCI estimates more than 35,700 people in the U.S. will be diagnosed with myeloma in 2023, which makes up about 1.5 percent of all cancer cases. The rate of new myeloma cases is about 7.1 per 100,000 people each year. Multiple myeloma comprises around 10 percent of blood cancers.  

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The signs of multiple myeloma can vary from person to person. Some cases (such as those caused by a form of the disease called smoldering multiple myeloma) don’t cause any noticeable symptoms. These cases are only detected after a blood or urine test for another condition.

CRAB is a mnemonic sometimes used by healthcare providers (HCPs) to describe multiple myeloma symptoms:

• C: Calcium levels in the blood are high (hypercalcemia)
• R: Renal (kidney) disease or failure symptoms, such as confusion, fatigue, itching, and nausea
• A: Anemia (low red blood cell count)
• B: Bone pain, usually in the hips, ribs, or spine

Bone pain is often the first sign of multiple myeloma. It may be the result of several factors, including:

• A compression fracture in the spine (small breaks in the vertebral bones)
• Lytic lesions (bone damage or destruction causing holes in various areas of bone)
• Osteoporosis (weakening and thinning of bones)

Other possible signs and symptoms of multiple myeloma include: 

• Severe, persistent fatigue
• Muscle weakness
• Numbness in an arm or leg
• Nausea or vomiting
• Unexplained weight loss 
• Easy bruising or bleeding
• Fever 
• Easily broken bones
• Frequent infections
• Brain fog or confusion 
• Constipation
• Increased thirst
• Frequent urination 

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Multiple myeloma occurs when a genetic mutation (an abnormal change) causes a single plasma cell to become cancerous. What triggers this change is not fully understood, although a combination of genetic and environmental factors is likely to play a role.  

The cancerous plasma cell grows and divides at a rapid rate, continuing to live on when a healthy cell would otherwise die at the end of its life span. Eventually, cancerous plasma cells build up in the bone marrow and crowd out healthy blood cells. M proteins produced by these abnormal plasma cells also accumulate and cause damage in the body, such as kidney problems. M protein is an atypical immunoglobin (blood protein) that’s produced by cancerous plasma cells.

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Researchers aren’t sure why some people develop multiple myeloma and others don’t, but a few factors that can increase a person’s risk of this blood cancer have been identified.

Established multiple myeloma risk factors include:

• Age: Most people who experience multiple myeloma are over the age of 60, with the average age at diagnosis being 70. Only 2 percent of cases occur in people younger than 40.
   
• Sex assigned at birth: People assigned male at birth have a slightly higher risk of multiple myeloma than people assigned female at birth.
   
• Race: Multiple myeloma is twice as common among Black people than white people. The reasons for this are still largely unclear.
   
• Family medical history: People with a first-degree blood relative (such as a parent or sibling) with multiple myeloma have a higher risk of this cancer. 
   
• Personal medical history: Someone with the precancerous condition monoclonal gammopathy of undetermined significance (MGUS) or a solitary plasmacytoma (a single mass of abnormal or cancerous plasma cells that occurs in bone or soft tissue) has an elevated risk of eventually developing multiple myeloma.
   
• Chemical exposures: Frequent or prolonged exposure to certain pesticides may increase the risk of multiple myeloma. Veterans of the Vietnam War (during which a chemical called Agent Orange was widely used to destroy vegetation) and workers in petroleum-related industries may have a heightened risk of multiple myeloma due to chemical exposures.
   
• Weight: Being overweight or obese is associated with an increased risk of developing multiple myeloma.

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There are two main types of multiple myeloma:

Smoldering (indolent) multiple myeloma

Smoldering (indolent) multiple myeloma (SMM) refers to cancer that doesn’t cause noticeable symptoms and may not require immediate treatment. As such, it is sometimes called asymptomatic multiple myeloma.

In this cancer, the level of abnormal monoclonal (M) proteins in the blood is 30 grams per liter (g/L) or higher, or 10 percent or more of the blood cells in the bone marrow are plasma cells.(Ordinarily, between 2 and 3 percent of bone marrow cells are plasma cells.) People with SMM should be periodically evaluated by an HCP for signs of worsening disease.

SMM is generally viewed as the step in between monoclonal gammopathy of undetermined significance (MGUS) and active multiple myeloma. MGUS is a precancerous condition that produces small amounts of abnormal M proteins. People with MGUS have a collective 1 percent chance per year of developing myeloma and, in rare cases, other diseases such as:

• Amyloidosis, a condition that causes an abnormal protein called amyloid to build up in various organs and tissue such as the brain, heart, kidneys, and spleen.
• Chronic lymphocytic leukemia, a type of leukemia that starts in white blood cells called lymphocytes.
• Lymphoma, a blood cancer affecting part of the body’s immune system called the lymphatic system, which consists of the lymph nodes, bone marrow, spleen, and thymus gland.

Active (symptomatic) multiple myeloma

Active (symptomatic) multiple myeloma is an active cancer that causes noticeable symptoms. Immediate treatment is usually recommended. Someone with this cancer can develop complications such as anemia, hypercalcemia (high blood calcium), kidney failure, a bone or soft tissue plasmacytoma, or bone damage.

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If an HCP suspects a person might have multiple myeloma, several tests may be performed to rule out or confirm a diagnosis.  

Blood and urine tests

Diagnosing multiple myeloma usually begins with a series of blood tests. This can include:

• Electrophoresis: This test checks for M proteins (produced by myeloma cells) in blood.
• Complete blood count (CBC): This blood test measures levels of red and white blood cells, along with the concentration of red blood cells and how much hemoglobin (the protein that helps deliver oxygen to tissues) they contain. 
• Blood chemistry test: This blood test measures levels of substances that could indicate cancer or another health concern. These substances include calcium, creatine (an amino acid and an indicator of kidney health), albumin (a protein produced by the liver), and lactase dehydrogenase (called LDH, an enzyme that can signal organ or tissue damage).  
• Quantitative immunoglobin test: Low levels of proteins called immunoglobulins in blood could indicate multiple myeloma.

Additional blood tests may be performed to screen for beta-2-microglobulin (a protein produced by myeloma cells), portions of M proteins called light chains (in a test called a serum-free light chain assay), and other possible indicators of blood cancer.

An HCP may also recommend a urine analysis that examines urine collected over a 24-hour period using an at-home test. This sample is screened for M proteins, which are referred to as Bence Jones proteins when they’re present in urine.

Imaging tests  

Imaging tests can uncover bone damage associated with multiple myeloma. An HCP may recommend one or more of the following imaging methods:

• X-ray: X-ray imaging uses a small amount of radiation to create images of bones. It’s often the first imaging test performed to check for skeletal signs of myeloma.
   
• Magnetic resonance imaging (MRI): MRI technology uses a magnetic field to create more detailed images of bones than X-rays. It can also show if bone marrow has been impacted by a plasmacytoma or myeloma cells.
   
• Computed tomography (CT): CT scans produce detailed, 3D images of bones and soft tissues by combining a series of cross-sectional pictures. It can reveal tumors and other irregularities associated with multiple myeloma.
   
• Positron emission tomography (PET): A PET scan (sometimes called a PET-CT scan) involves injecting a very small amount of radioactive sugar into the body. Active cancer cells absorb more of this sugar than healthy cells and show up brighter on a CT scan.

Bone marrow tests

Bone marrow tests like biopsies and aspirations are an important part of confirming a multiple myeloma diagnosis. Bone marrow features solid and liquid components. A bone marrow biopsy involves drawing out a small sample of solid tissue with a needle. A bone marrow aspiration uses a needle to collect a small sample of fluid for testing.

Bone marrow biopsy and aspiration are usually performed at the same time, most often in the pelvic (hip) bone. Liquid and solid samples of bone marrow are then evaluated for myeloma cells under a microscope by a pathologist (a medical doctor who specializes in evaluating cells for disease). 

HCPs also use bone marrow tests to learn more about the cancer’s characteristics and help develop appropriate multiple myeloma treatment plans. For instance, a fluorescence in situ hybridization (FISH) test provides insight on the cancerous plasma cells’ genetic makeup, and genomic sequencing can uncover what abnormal changes took place in the cancer cells’ DNA (genetic material). This study of genetic changes in cells is known as cytogenetics.

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Many cancers are staged according to the TNM (tumor, node, metastasis) system, but blood cancers like multiple myeloma are different. The Revised International Staging System (R-ISS) is commonly used in the U.S. to describe the extent of a person’s multiple myeloma. This system focuses on four key factors that are linked to fast-growing, aggressive blood cancers and can influence a person’s multiple myeloma prognosis.

These factors include:

• The cancer’s cytogenetics: This refers to gene abnormalities. Certain abnormal changes in or between chromosomes (threadlike structures of DNA) are associated with poorer outcomes in multiple myeloma cases.  
• The level of lactase dehydrogenase (LDH) in blood: Generally, the greater the amount of LDH in the blood, the poorer the prognosis.
• The level of albumin in blood: Low levels of albumin in the blood can indicate more aggressive multiple myeloma.
• The level of beta-2-microglobulin in blood: High levels of this protein in the blood suggest more aggressive multiple myeloma.

Based on these factors, multiple myeloma is assigned a stage between 1 and 3. Stage 1 multiple myeloma tends to grow slowly, while stage 3 multiple myeloma is aggressive and spreads rapidly.

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Multiple myeloma treatment is usually overseen by a medical doctor who specializes in evaluating and treating cancer, called an oncologist. Your healthcare team might also include a hematologist (a medical doctor who specializes in treating blood diseases), among other HCPs. 

Smoldering multiple myeloma (SMM) may not require immediate treatment. Often, someone with SMM is simply monitored by their HCP for warning signs of active multiple myeloma. This approach is referred to as “watchful waiting.”

Prompt medical intervention is usually recommended in cases of active multiple myeloma. While there’s no known cure for this cancer, treatment can help alleviate symptoms, slow the cancer’s progression, and prolong life.

Multiple myeloma can be managed for years with treatment. In fact, you may achieve partial or full multiple myeloma remission if the disease responds well to treatment. Partial remission means your tumors have shrunk and you have fewer cancer cells present, although you may still experience some symptoms and some tests may still find cancer cells in your body. Full remission means there’s a period when symptoms resolve and the disease isn’t detectable. 

Multiple myeloma treatment typically involves a combination of therapies. Treatments may be given at the same time or one after the other, depending on the details of your diagnosis, other health conditions you may have, and your care preferences.

Common treatments for multiple myeloma include:

Chemotherapy 

Chemotherapy (chemo) uses potent anti-cancer drugs to attack myeloma cells throughout the body. It may be given as a pill or administered intravenously in multiple cycles. Chemo was once the main form of treatment for multiple myeloma, but advances in cancer care have diversified treatment options for patients.

Medication

Corticosteroid medications like prednisone and dexamethasone help reduce inflammation in the body and reduce cancer-related pain. They may also be prescribed to ease chemo side effects like nausea and vomiting. Corticosteroids are only recommended for short-term use since long-term usage may worsen bone damage and further suppress the immune system. 

Immunomodulators like thalidomide and lenalidomide are another type of medication used in multiple myeloma treatment. These drugs help bolster the immune system and prevent new blood vessels from developing and fueling myeloma cells. 

Many people with multiple myeloma are also prescribed bone modulators. These medications, including zoledronic acid, pamidronate, and denosumab, can help ease bone pain, strengthen bones, and reduce the risk of fractures.

Targeted therapy  

Targeted therapy uses drugs like monoclonal antibodies (elotuzumab, isatuximab, and daratumumaband) and proteasome inhibitors (bortezomib, carfilzomib, and ixazomib) to disrupt processes that feed cancer growth. While this treatment doesn’t focus on destroying the myeloma cells themselves, it targets specific chemicals in cancer, helping prevent the growth and spread of cancer while limiting damage to surrounding healthy tissues.

Immunotherapy 

Immunotherapy harnesses the disease-fighting abilities of the body’s own immune system to target myeloma. Ordinarily, cancer cells can thrive by hiding from the immune system. Immunotherapy helps the immune system better identify and attack cancer cells. 

The most common type of immunotherapy for multiple myeloma is chimeric antigen receptor (CAR) T-cell therapy. This method uses drugs (such as idecabtagene vicleucel or ciltacabtagene autoleucel) to target a protein called B-cell maturation antigen (BCMA) on the surface of cancer cells.

CAR T-cell therapy involves separating T-cells (one of the main lymphocytes of the immune system) from other components of the patient’s blood in a process known as leukapheresis. The T-cells are then sent to a lab where they’re multiplied and genetically altered to include CARs. These are receptors that help T-cells adhere to the BCMA proteins on cancer cells. The altered T-cells are then infused back into the patient so that they may target cancer cells.

Other drug therapies

Your multiple myeloma treatment plan may also include other drug therapies, including:  

• Bispecific T-cell engagers (BiTEs): Bispecific antibodies, which are designed to adhere to two different targets, are a more recent advance in cancer treatment. BiTEs are a type of bispecific antibody that work by attaching to myeloma cells as well as T-cells. This brings the two cells together and allows the immune cell to attack the cancer.
• Nuclear export inhibitors: Selinexor is a nuclear export inhibitor. This is a type of drug that disrupts a myeloma cell’s ability to transport an important protein from its nucleus (center) to other parts of the cell. When this process can’t be completed, the cell dies.

Radiation therapy

Radiation therapy uses high-powered, precisely aimed radiation to destroy cancer cells in a specific area. In multiple myeloma, radiation therapy may be used to attack a collection of myeloma cells that form a plasmacytoma (a bone or soft tissue tumor). It can also help treat bone pain caused by myeloma in areas that have not responded well to other therapies.  

Bone marrow transplantation

A bone marrow transplant (also called a stem cell transplant) replaces cancerous bone marrow with hematopoietic stem cells. These are blood-forming cells that can develop into healthy platelets, red blood cells, and white blood cells. 

Bone marrow transplantation involves collecting hematopoietic stem cells from the patient’s blood, then administering high doses of chemotherapy to destroy cancerous bone marrow. The stem cells are then administered back to the patient, where they begin to create healthy blood cells and replenish bone marrow.

A bone marrow procedure that uses the patient’s own hematopoietic stem cells is called an autologous bone marrow transplant. Other procedures may use healthy stem cells from a carefully matched donor. This type of transplant is known as an allogenic bone marrow transplant.

Clinical trials

A clinical trial is a research study with human participation. There are several clinical trials underway with the goal of improving outcomes for patients with multiple myeloma. For example, some trials focus on developing new treatments, while others aim to improve the effectiveness of existing therapies.

Because many multiple myeloma clinical trials involve evaluating the safety and effectiveness of new treatments, it’s important to note that participation comes with possible risks. Talk to your HCP if you’re interested in learning more about clinical trials for multiple myeloma. You can also find ongoing myeloma clinical trials that are sponsored or supported by the National Cancer Institute (NCI) by visiting their website.

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Multiple myeloma can initiate a ripple effect of health issues. Some of the most common complications associated with this blood cancer include:

• Anemia: When myeloma cells drive out healthy cells from the bone marrow, it can result in a lack of red blood cells. Around 75 percent of people with multiple myeloma present with anemia.    
• Frequent infections: A lack of healthy white blood cells, chemotherapy side effects, and other myeloma-related factors may hinder the immune system and cause frequent infections. This often includes pneumonia, COVID-19, and urinary tract infections.
• Bone damage: Bone erosion or thinning of bones (known as osteoporosis) can result from growing plasmacytomas or excess amounts of substances called cytokines produced by myeloma cells.
• Hypercalcemia: Myeloma-related bone erosion can contribute to elevated calcium levels in the blood.
• Hyperviscosity: Blood may thicken as a result of a buildup of M proteins that can slow blood flow through smaller vessels.
• Kidney failure: Myeloma may cause dysfunction in one or both kidneys (sometimes referred to as “myeloma kidney”). An excess of blood calcium and M proteins can overwork kidneys as they try to clean the blood. Kidney failure affects between 20 and 40 percent of people with multiple myeloma at diagnosis, and more than half experience impaired kidney function at some point during their time with multiple myeloma.    
• Thrombosis: A combination of factors related to myeloma, co-existing conditions, and cancer treatment drugs may contribute to blood clotting in veins or arteries that blocks blood flow and increases heart attack and stroke risk.  
• Peripheral neuropathy: Multiple myeloma, its treatment, or a combination of both may damage nerves located outside of the spinal cord and brain. This may cause weakness or pain in the arms or legs.  

Many multiple myeloma complications can be treated or managed through medication or by receiving vaccinations to help prevent infections. If you develop kidney failure, you’ll likely receive dialysis. This is an inpatient treatment that cleans your blood—a job typically performed by healthy kidneys.

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It’s always smart to consult with your HCP if you develop any symptoms that concern you, such as unexplained fatigue, weakness, or bone pain that doesn’t improve in a few days. Your HCP can help you identify the source of your symptoms and recommend appropriate treatment.

If you’ve already received a multiple myeloma diagnosis, you should promptly visit your HCP if you develop worsening symptoms or possible signs of multiple myeloma complications. This might include frequent infections, high fever, shortness of breath, leg or arm swelling, and vomiting, among other changes in health.

What questions should you ask your healthcare provider?    

Plenty of emotions can accompany a multiple myeloma diagnosis, including confusion or anxiety about the condition itself and what it means for you (or a loved one). Keeping a running list of questions to ask your HCP can help you make informed, confident decisions about your care and get the most out of your medical appointments.

A few basic questions you may want to add to your list include: 

• Should I get a second or third opinion?
• Is my multiple myeloma smoldering or active?
• What is the main goal of treatment for my specific case?  
• Are my kidneys affected?  
• Can you explain my treatment options? What are the risks and benefits of each?
• Can I receive outpatient treatment or will I need to stay in a hospital?
• How will my everyday routine be affected by multiple myeloma and its treatment?
• Will I need a bone marrow transplant?
• How can I help relieve side effects from treatment or the cancer itself?
• Which symptoms require prompt and/or emergency medical care? How can I tell the difference?
• Who should I call if I have questions?
• How can I manage my other health conditions (if applicable) with multiple myeloma?
• Can you refer me to a supportive care professional, such as a clinical social worker or psychologist?  
• If I need financial assistance during cancer treatment, where can I turn?  
• What steps should I take to plan for the future?

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Multiple myeloma isn’t preventable at this point, but research is focused on ways to identify precursor diseases like MGUS and SMM early and to prevent these conditions from turning into active, symptomatic multiple myeloma. Some of the same drug therapies used in active multiple myeloma treatment are being investigated as treatment for MGUS and SMM, with a goal of stopping cancer before it starts.

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Multiple myeloma is a complex disease with no known cure. Still, early diagnosis and treatment can help people manage the disease and live well for many years, sometimes decades. Treatments for blood cancers like multiple myeloma are steadily improving, and more people with this condition are living better, longer.

According to the NCI’s Surveillance, Epidemiology, and End Results (SEER) Program, the five-year survival rate for myeloma is 59.8 percent. This means nearly 60 percent of people with multiple myeloma are still alive five years after receiving their diagnosis, according to data collected between 2013 and 2019. (Compare that to a 24.8 percent five-year survival rate in 1975.) Data also shows that age-adjusted multiple myeloma death rates dropped an average of 1.3 percent each year between 2011 and 2020.

It's important to remember that no two cases of cancer are the same. Several factors will influence your multiple myeloma prognosis, including your age, overall health, the stage of your myeloma at diagnosis, and the individual characteristics of your cancer.

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There’s no one way to live with multiple myeloma. Your cancer journey is unique, so it’s best to work with your HCP to develop a treatment plan that makes the most sense for the type and severity of your disease, as well as your treatment preferences. 

That being said, many people with multiple myeloma find it helpful to follow some general recommendations when dealing with the ups and downs of cancer and its treatment. These include prioritizing:

Mental health  

The effects of a serious diagnosis like multiple myeloma extend beyond the physical. Many people with cancer experience emotional distress that impacts their daily routine. In fact, around 25 percent of people with multiple myeloma develop anxiety or depression.

Caring for someone with multiple myeloma can also pose challenges. A 2022 study published in Blood Advances found that anxiety levels may actually be higher among caregivers of loved ones with multiple myeloma than the patients themselves.

Whether you have multiple myeloma or are a caregiver for someone with cancer, it’s important to take steps to protect your mental health. You may find it helpful to share your feelings with trusted loved ones or consult with a licensed mental health provider, such as a psychologist, psychiatrist, counselor, or clinical social worker.

Many in-person and online support groups are available for people with multiple myeloma and their caregivers. Implementing stress management techniques, such as practicing yoga, journaling, or performing deep breathing exercises, can also be helpful.

Nutrition

Good nutrition is essential to living well with (or without) cancer. The Leukemia & Lymphoma Society (LLS)—a national authority on blood cancers—emphasizes the importance of a  nutrient-rich diet for people with multiple myeloma.

The LLS recommends:

• Eating a variety of fruits and vegetables every day
• Enjoying plenty of whole grains, such as oatmeal, whole wheat bread, and brown rice
• Eating protein-rich foods to help boost the immune system, including lean meats, nuts and nut butters, eggs, beans, and low-fat dairy products
• Opting for bland foods that are easy on the stomach (this means avoiding spicy, fried, or especially strong-smelling foods)
• Eating multiple, small meals throughout the day (around every three hours or so) rather than large meals
• Choosing healthy fats (such as omega-3 fatty acids and monounsaturated fats) found in whole foods such as nuts, avocados, olive oil, and fatty fish like salmon, sardines, and tuna
• Cutting back on alcohol or avoiding it altogether  
• Limiting sweets and added sugars  
• Staying hydrated by drinking healthy fluids such as water throughout the day, and eating water-rich foods such as melons, berries, leafy greens, and cucumbers

Physical activity

Multiple myeloma is a physically taxing disease, so the thought of prioritizing regular exercise during treatment may seem like an uphill climb. A growing body of research shows, however, that staying active (to the best of one’s ability) while living with cancer can boost both mental and physical well-being.

According to a 2023 review of studies published in the Journal of the Advanced Practitioner in Oncology, study participants with multiple myeloma who were the most physically active experienced improvements in blood counts, mood, pain, fatigue, and sleep. Researchers advise multiple myeloma patients to exercise at least twice a week. Cardiovascular exercises (such as cycling or brisk walking) combined with body weight or free-weight training activities (like sit-ups or light weightlifting) can enhance range of motion and strengthen muscles and joints.

Exercise is beneficial for just about everyone, but it’s important to consult with your HCP before starting or making substantial changes to your workout routine. They can suggest exercises or a fitness schedule that’s suited to your age, stage of cancer, and physical abilities. Your HCP may also refer you to a specialist, such as a clinical exercise physiologist, who can help you manage your cancer symptoms and improve your overall health through safe physical activity.  

Multiple myeloma can be managed well—often for many years. To learn more about living with multiple myeloma or how you can support a loved one with the disease, contact your HCP or browse information from trusted organizations like the Multiple Myeloma Research Foundation, the Leukemia & Lymphoma Society, or the American Cancer Society.

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• Questions to Ask Your Doctor About Multiple Myeloma Recurrence  
• 5 Mistakes to Avoid During Multiple Myeloma Remission 
• Why Multiple Myeloma Remission Doesn’t Mean Treatment is Over