Understanding the Leading Causes of End-Stage Multiple Myeloma

Multiple myeloma is a chronic (long-term) blood cancer that affects plasma cells made in the bone marrow, which is spongy tissue found inside bones. While people with multiple myeloma can live for years with treatment, the condition can become fatal when it no longer responds to treatment or when it progresses and damages major organs, such as the kidneys.

Plasma cells are a type of white blood cell that form in the bone marrow and make antibodies. Antibodies are proteins that help your body fight infections. In multiple myeloma, abnormal plasma cells build up in the bone marrow and crowd out healthy blood-forming cells, including red blood cells, white blood cells, and platelets. Platelets are small parts of larger cells that help form clots and stop bleeding. 

When someone with multiple myeloma passes away, it’s usually not from the cancer itself, but from complications the condition causes. Cancerous plasma cells produce abnormal antibodies called M-proteins that can’t fight infections. These proteins can also build up in the body and damage the bones, kidneys, and other organs, causing life-threatening and fatal complications.

The causes of death in multiple myeloma often affect the immune system and several organs in the body.

Impaired Immune Function

Infections are the leading cause of death in people with multiple myeloma. Multiple myeloma weakens your immune system, making it harder for your body to fight off infections. This happens for a few reasons. First, myeloma cells multiply in the bone marrow and crowd out healthy blood-forming cells, including white blood cells that help protect against and fight infections.

Healthy plasma cells make antibodies to fight off infection-causing microorganisms, including viruses, bacteria, fungi, and parasites. In multiple myeloma, cancerous plasma cells produce large amounts of an abnormal antibody, M-protein, that can’t fight infections. Not being able to properly fight infections weakens the immune system, making you more vulnerable to infectious diseases.

Some treatments for multiple myeloma, such as chemotherapy and steroids, can also suppress the immune system. These medications can lower the number of neutrophils, a type of white blood cell that helps fight bacterial infections. When neutrophil levels drop too low (a condition called neutropenia), the risk of infection increases. 

People with multiple myeloma are at higher risk of serious infections, including:

• Pneumonia
• Urinary tract infections (UTIs)
• Gastrointestinal infections
• Shingles, a reactivation of the herpes zoster/chickenpox virus.
• Sepsis

Kidney Damage

Kidney failure is the second most common cause of death in people with multiple myeloma. At the time of diagnosis, about half of all people with the condition already show signs of weak kidney function. People who have kidney damage when diagnosed with multiple myeloma have a higher risk of complications and death.

Your kidneys filter waste, excess fluids, and toxins from your blood. In multiple myeloma, cancerous plasma cells make abnormal proteins called monoclonal light chains. These proteins are too large for the kidneys to filter properly. As they build up, they can clog the kidneys’ nephrons, the tiny tubes that filter waste from blood, causing permanent kidney damage. These protein-related blockages are responsible for about 85% of kidney complications in people with multiple myeloma.

When kidney function declines, your body can’t filter and remove waste properly. This can lead to a buildup of toxins, edema (fluid overload), and imbalances in electrolytes, which can be life-threatening. 

Disease Progression

Multiple myeloma is a relapsing and remitting disease, meaning it can respond to treatment for a time and disappear temporarily (remits), but often returns (relapses). Each relapse may be more difficult to treat than the last. Over time, the cancer can stop responding to therapy altogether, becoming what’s known as treatment-resistant or refractory multiple myeloma.

As the disease progresses, cancerous plasma cells multiply quickly and can crowd out healthy cells in the bone marrow. This prevents your body from making enough red blood cells, white blood cells, and platelets.

A severe drop in red blood cells (anemia) lowers the amount of oxygen reaching your organs. Low white blood cell counts weaken your immune system, making you more likely to get serious infections. Low platelet counts increase the risk of uncontrolled bleeding. When these complications progress and no longer respond to treatment, vital organs can begin to shut down, which may result in death.

Bone Loss and Hypercalcemia

Multiple myeloma can weaken bones and increase the risk of fractures (breaks) when cancerous plasma cells stop the normal process of bone breakdown and rebuilding. As bones break down, calcium, a mineral that helps maintain bone and tooth health, is released into the bloodstream. This can lead to hypercalcemia, which is a condition where there are high levels of calcium in the blood.

Symptoms of hypercalcemia include:

Severe hypercalcemia is a medical emergency that requires immediate treatment to lower calcium blood levels. Without prompt treatment, hypercalcemia can disrupt normal heart function, leading to cardiac arrest and death. 

Heart and Lung Complications

Multiple myeloma and some of its treatments, particularly immunomodulatory drugs (IMiDs), increase the risk of blood clots, such as deep vein thrombosis (DVT) or pulmonary embolism (PE). A PE occurs when a blood clot that forms in a deep vein, such as in a leg, travels to the lungs and blocks blood flow, which can be life-threatening.

Some myeloma medications may damage the heart or lungs and increase the risk of heart failure. Generally, the longer you take medications to treat multiple myeloma, the higher your risk for heart and lung complications, which can be fatal without prompt treatment.

Life expectancy with multiple myeloma varies from person to person. Several factors influence your prognosis (outcome), including your age, stage and subtype of myeloma when you receive a diagnosis, and your overall health. A subtype, in this case, is a more specific type of myeloma, like smoldering multiple myeloma. 

Based on current cancer statistics across the United States, the overall five-year relative survival rate for people with multiple myeloma is 62.4%. That means about 62 out of 100 people with myeloma are still alive five years after diagnosis. 

Research advancements and new treatment discoveries have improved the outlook for people with multiple myeloma in recent years. Modern therapies, including targeted drugs, immunotherapy, and stem cell transplants, help many people achieve long periods of remission. While there’s no cure for multiple myeloma, these treatments have made it possible for many people to live fulfilling, active lives for years after their diagnosis.

Multiple myeloma is a blood cancer that affects plasma cells in the bone marrow. People with multiple myeloma may pass away from complications such as severe infections due to a weakened immune system, kidney failure, disease progression with treatment-resistant cancer, or heart and lung complications related to the disease or their treatments.

While the overall five-year survival rate is about 62%, outcomes can vary based on age, condition stage, subtype, and overall health. With current treatment advances, many people with multiple myeloma live for years with a good quality of life.