Plasma cell myeloma, more commonly known as multiple myeloma, is a cancer that develops in specialized white blood cells called plasma cells, which normally help protect the body from infections by producing antibodies. When these cells become cancerous, they multiply uncontrollably in the bone marrow, crowding out healthy blood cells and producing abnormal proteins that can damage organs and bones.

Understanding the Disease Pattern Around the World

Plasma cell myeloma represents a relatively uncommon form of cancer when compared to other types of malignancies. In the United States, it accounts for approximately 1.6 percent of all cancer cases diagnosed each year^[15]. Within the category of blood-related cancers, however, it holds more significance, making up roughly 10 percent of all blood and bone marrow malignancies^[15]. In 2015, medical professionals diagnosed around 28,850 new cases in the United States alone, and the disease was responsible for more than 11,000 deaths during that same year^[15].

The disease shows clear patterns in terms of who it affects. Age plays the most important role in determining risk. People younger than 45 years old very rarely develop this condition^[3]. The vast majority of patients, about 85 percent, are older than 65 when they receive their diagnosis^[15]. The median age at diagnosis sits at around 70 years, with only 15 percent of those diagnosed being younger than 65^[7]. A median represents the middle point in a group, meaning half of patients are younger than this age and half are older.

Gender also influences who develops the disease. Men experience plasma cell myeloma more frequently than women, with the ratio being approximately 1.4 men for every woman diagnosed^[7]. Perhaps most striking is the difference seen across racial groups. Black individuals develop this cancer at rates more than twice as high as White individuals^[3][7]. Additionally, Black patients tend to present with the disease at younger ages compared to other racial groups^[7].

What Causes Plasma Cell Myeloma

Scientists still do not fully understand why some people develop plasma cell myeloma while others do not^[3][4]. What medical researchers do know is that the disease begins when changes occur in the genetic material of plasma cells. These cells are a type of white blood cell that develops from B lymphocytes, which are infection-fighting cells made in the bone marrow^[8].

Under normal circumstances, when bacteria or viruses enter the body, some B cells transform into plasma cells. These plasma cells then manufacture antibodies, which are specialized proteins designed to identify and attack germs, preventing infection and disease^[8]. In plasma cell myeloma, however, genetic mutations cause these cells to behave abnormally. The mutations lead plasma cells to divide and multiply out of control^[5].

These genetic changes are not inherited from parents. Instead, they develop over the course of a person’s lifetime^[5]. Researchers have identified that genetic abnormalities appear in the cells of about 90 percent of patients with this disease^[7]. Particularly, frequent alterations involve chromosome 14, and multiple genetic changes appear to occur in steps as the disease progresses^[7]. Other genes that may contribute to the uncontrolled growth of plasma cells include NRAS, KRAS, and BRAF^[7].

The disease typically develops gradually through stages. Most cases of plasma cell myeloma appear to originate from a condition called monoclonal gammopathy of undetermined significance, or MGUS^[4][7]. This is a benign condition where abnormal plasma cells are present but do not cause symptoms or health problems. MGUS is relatively common, found in more than 3 percent of people over age 50^[7]. While MGUS itself is not dangerous, it progresses to plasma cell myeloma at a rate of about 1 percent per year^[7]. Before becoming full myeloma, the condition passes through another stage known as smoldering myeloma^[4].

Who Is at Higher Risk

Several factors increase the likelihood of developing plasma cell myeloma, though having these risk factors does not guarantee someone will develop the disease. Age stands as the most significant risk factor. Because the disease predominantly affects older adults, anyone approaching or past middle age faces incrementally higher risk as years pass^[3].

Being male increases risk compared to being female^[3][5]. Black individuals carry substantially higher risk compared to people of other races, with rates approximately double those seen in White populations^[3][5].

Obesity and being overweight represent known risk factors for developing plasma cell myeloma^[3][4][5][7]. This connection suggests that maintaining a healthy weight through diet and physical activity may play some role in prevention, though more research is needed to confirm this relationship.

Family history appears to play a minor role. Rarely, more than one member of the same family develops plasma cell myeloma, but experts do not fully understand why this connection exists^[5]. The condition is not considered hereditary, meaning it does not pass directly from parent to child through genes present at birth.

Certain environmental exposures may contribute to risk. In rare cases, exposure to radiation, including medical X-rays or other forms of ionizing radiation, which is a type of energy that can damage cells, may increase the likelihood of developing the disease^[3][4]. Some occupations carry increased risk due to workplace exposures^[4]. Specifically, exposure to certain chemicals such as pesticides, fertilizers, aromatic hydrocarbon solvents, and Agent Orange has been linked to higher rates of plasma cell myeloma^[4][5][7]. Workers in jobs involving these substances should follow safety guidelines to minimize exposure.

Recognizing the Symptoms

One of the challenging aspects of plasma cell myeloma is that many people have no symptoms at all in the early stages of the disease^[2][4]. In these cases, doctors may discover abnormalities during routine blood or urine tests performed for other reasons, when elevated protein levels appear^[3]. As the disease advances, however, various symptoms can emerge.

Bone pain represents the most common early symptom that brings patients to medical attention. This pain typically affects the back, but can also occur in the ribs, chest, pelvis, head, or upper legs^[2][3][5]. The pain develops because cancerous plasma cells form tumor masses in bones and produce chemicals that break down bone tissue while preventing new bone from forming^[13]. This process weakens bones, making them prone to breaking easily, sometimes with minimal trauma^[2][3].

Because myeloma cells crowd out normal blood cells in the bone marrow, patients frequently develop anemia, which is a condition of having too few red blood cells^[2][5]. Anemia causes tiredness, weakness, and a pale appearance^[2][5][13]. Some patients describe feeling extremely fatigued or experiencing mental fogginess and confusion^[2].

When healthy white blood cells and plasma cells become depleted, the immune system cannot function properly, leaving patients vulnerable to frequent infections^[2][5]. Pneumonia and other bacterial infections occur more commonly in people with this disease^[3][5]. Similarly, low platelet counts, which are blood cells that help with clotting, can result in unusual bruising or bleeding^[5][13].

Other symptoms may include digestive complaints such as nausea, constipation, and loss of appetite^[2][5]. Some patients experience unexplained weight loss^[2][3][5]. Neurological symptoms like numbness or tingling in the arms and legs can occur due to nerve damage^[5]. Increased thirst and frequent urination may develop in some cases^[2]. Fever without an obvious cause and difficulty breathing are additional possible symptoms^[3].

In some patients, weakness in the arms or legs develops^[3]. These symptoms can also arise from many other, less serious conditions. Anyone experiencing persistent or concerning symptoms should consult with a doctor for proper evaluation^[2].

Steps to Lower Your Risk

Because scientists do not yet fully understand what causes plasma cell myeloma, specific prevention strategies remain limited. However, addressing modifiable risk factors may help reduce the likelihood of developing the disease.

Maintaining a healthy weight appears important, since obesity represents a known risk factor^[3][5][7]. Eating a balanced diet rich in fruits, vegetables, whole grains, and lean proteins while limiting processed foods and excess calories can help achieve and maintain a healthy body weight. Regular physical activity not only helps with weight management but provides numerous other health benefits that support overall well-being.

Minimizing exposure to potentially harmful chemicals represents another prudent step. People working in occupations where exposure to pesticides, fertilizers, aromatic hydrocarbon solvents, or other industrial chemicals occurs should strictly follow workplace safety protocols, use appropriate protective equipment, and ensure adequate ventilation^[4][5][7].

Limiting unnecessary exposure to radiation is also advisable, though the connection between radiation and plasma cell myeloma appears relatively weak^[3]. Medical imaging using radiation should only be performed when medically necessary and the benefits outweigh potential risks.

Since plasma cell myeloma often develops from MGUS, people known to have this precursor condition should maintain regular follow-up appointments with their healthcare provider. While MGUS itself requires no treatment, monitoring can detect if and when it progresses to a more serious stage, allowing for earlier intervention.

How the Disease Affects the Body

Understanding what happens inside the body when plasma cell myeloma develops helps explain why symptoms occur and why the disease causes such diverse problems. The disease begins in the bone marrow, the soft, spongy tissue inside bones where blood cells are produced^[2][5]. Normal bone marrow contains only a small percentage of plasma cells, but in people with myeloma, these abnormal plasma cells accumulate and multiply excessively^[6].

As cancerous plasma cells build up, they physically crowd out healthy blood cells^[2][5]. This crowding prevents the bone marrow from producing adequate numbers of red blood cells, white blood cells, and platelets. The shortage of red blood cells leads to anemia and its associated fatigue and weakness. Insufficient white blood cells compromise the immune system’s ability to fight infections. Low platelet counts impair blood clotting, increasing bleeding and bruising risk.

Instead of producing helpful antibodies that fight infection, the cancerous plasma cells manufacture abnormal proteins called M proteins or monoclonal proteins^[2][5][8]. These proteins do not help defend against germs and instead cause harm. The abnormal proteins can accumulate in the bloodstream, causing the blood to become overly thick, a dangerous condition called hyperviscosity syndrome^[2][5]. When blood becomes too thick, it cannot flow properly through small vessels, potentially leading to serious complications.

M proteins can also damage organs, particularly the kidneys^{[2][5][8][13]}. As these abnormal proteins pass through the kidneys, they can cause kidney dysfunction or even kidney failure, resulting in symptoms like nausea, loss of appetite, and changes in urination patterns^[13]. Sometimes the abnormal proteins deposit in tissues throughout the body, causing a condition called amyloidosis, where protein buildup damages the heart, kidneys, nerves, and other organs^[2][5].

The myeloma cells themselves cause significant damage to bones. They produce substances that activate cells responsible for breaking down bone while simultaneously inhibiting cells that build new bone^[8][13]. This imbalance leads to areas of bone destruction called lytic lesions, which appear as holes in bones on imaging tests^[15]. The weakened bones become prone to fractures and cause persistent pain. Additionally, as bone breaks down, calcium releases into the bloodstream, potentially causing hypercalcemia, or abnormally high calcium levels^{[2][5][13][15]}. High calcium can cause confusion, constipation, excessive thirst, frequent urination, and other problems.

Myeloma cells can also form solid tumor masses called plasmacytomas^[2][8][11]. When only one tumor exists, doctors call the condition solitary plasmacytoma. When multiple tumors develop throughout the skeleton, the term multiple myeloma applies. Sometimes plasma cell tumors grow outside bones in soft tissues like muscles or organs, called extramedullary plasmacytomas^[3][8][11].

The complex nature of how plasma cell myeloma affects multiple body systems explains why treatment requires a comprehensive approach addressing not just the cancer cells themselves, but also the various complications they cause. Understanding these mechanisms helps patients and families grasp why certain symptoms occur and why multiple types of treatments may be necessary.