Plasma Cell Myeloma

Plasma cell myeloma is a cancer that develops in a type of white blood cell called a plasma cell, where abnormal cells build up in bone marrow and can affect bones, kidneys, and blood cells throughout the body.

multiple myeloma, myeloma, myelomatosis, Kahler’s disease

Table of contents

• What is plasma cell myeloma
• Types of plasma cell neoplasms
• Symptoms
• Causes and risk factors
• Diagnosis
• Treatment
• Complications
• Statistics

What is plasma cell myeloma

Plasma cell myeloma is a cancer that forms in plasma cells, which are a type of white blood cell made in the bone marrow. Bone marrow is the soft matter inside bones where blood cells are made^[2]. Normally, plasma cells help the body fight infections by making proteins called antibodies. These antibodies find and attack germs to protect against disease^[2].

In plasma cell myeloma, cancerous plasma cells build up in the bone marrow and crowd out healthy blood cells. Rather than make helpful antibodies, the cancer cells make abnormal proteins that don’t work properly^[2]. The plasma cells also make a protein called M protein that is not needed by the body and does not help fight infection. These abnormal proteins build up in the bone marrow and can cause the blood to thicken or damage the kidneys^[8].

The cancerous plasma cells can form tumor masses in the bones. When there are many tumors in the bones, the condition is called multiple myeloma^[3]. The disease can spread throughout the body, affecting multiple sites including bones, skin, muscles, and lungs^[13].

• Bone marrow
• Bones
• Kidneys
• Blood

Types of plasma cell neoplasms

Plasma cell neoplasms include several conditions that range from non-cancerous to cancerous. Some plasma cell neoplasms are benign, meaning they are not cancer, while others are malignant, meaning they are cancer^[8].

Monoclonal gammopathy of undetermined significance (MGUS) is not cancer but can become cancer. In this condition, less than 10% of the bone marrow is made up of abnormal plasma cells. The abnormal plasma cells make M protein, which is sometimes found during routine blood or urine tests. In most patients, the amount of M protein stays the same and there are no symptoms or health problems. However, in some patients, MGUS may later become a more serious condition or develop into cancer such as multiple myeloma^[8].

Plasmacytoma occurs when the abnormal plasma cells are in one place and form one tumor. Sometimes plasmacytoma can be cured. There are two types. In isolated plasmacytoma of bone, one plasma cell tumor is found in the bone, and less than 10% of the bone marrow is made up of plasma cells. In extramedullary plasmacytoma, one plasma cell tumor is found in soft tissue but not in the bone or bone marrow. These commonly form in tissues of the throat, tonsil, and areas around the nose^[8].

Multiple myeloma is the most common type of plasma cell tumor. In about 90% of patients, the disease is present in multiple sites throughout the body^[13]. This form develops in the bone marrow and can spread throughout the body. Multiple myeloma cells are abnormal plasma cells that build up in the bone marrow and form tumors in many bones of the body^[8].

Plasma cell leukemia is a rare and aggressive variation. Malignant cells accumulate in bone marrow and circulate in high numbers in the bloodstream. It is defined by the presence of more than a certain number of peripheral blood plasma cells or when they account for more than 20% of white blood cells^[12].

Symptoms

Early in plasma cell myeloma, there might be no symptoms. Sometimes the disease is found when a blood or urine test is done for another condition, and a higher than normal level of protein is found^[3]. Many patients present with only laboratory abnormalities such as anemia, kidney disease, and elevated protein levels^[15].

When signs and symptoms do occur, they can include bone pain, especially in the spine, chest, hips, back, or ribs^[2][3]. Bone pain is often the first symptom people notice^[5]. Other symptoms include nausea, constipation, loss of appetite, mental fogginess or confusion, tiredness, infections, weight loss, weakness, and increased thirst or urination^[2].

Since myeloma can crowd out normal blood cells, patients typically suffer from low blood counts. Low red blood cells lead to anemia, with symptoms of fatigue, weakness, and paleness. Low platelet counts can result in abnormal bruising and bleeding. Low white blood cell and plasma cell counts can lead to frequent infections, especially pneumonia^[13]. Patients may also experience numbness or tingling in the arms or legs^[5].

As myeloma is more advanced, symptoms may include bones that break easily, fever for no known reason, trouble breathing, and weakness of the arms or legs^[3].

Causes and risk factors

Scientists don’t understand why some people get myeloma and others don’t. The exact cause of plasma cell myeloma is unknown^[3][4]. Medical experts aren’t sure what causes it, but they do know that it happens when there’s a change in plasma cells. These changes cause plasma cells to divide uncontrollably. These aren’t mutations you’re born with but rather happen over your lifetime^[5].

Changes in genetic material are detected in 90% of plasma cells in patients with multiple myeloma. These genetic alterations lead to the progression from conditions like MGUS to multiple myeloma in some people^[4][15].

Age is the most significant risk factor for developing myeloma. People younger than 45 years old rarely develop the disease. Most people are diagnosed between ages 40 and 70, with a median age of diagnosis around 69 to 70 years^[3][5][7].

Men are more likely than women to develop myeloma^[3][5]. Myeloma is more than twice as common among Black people as among White people. Blacks have a twofold higher incidence compared with whites and present at a younger age^[3][15].

Rarely, more than one family member has multiple myeloma, though experts don’t know why there’s a link. The condition isn’t hereditary^[5]. Being overweight and having obesity are linked with a higher risk of getting multiple myeloma^[3][5].

In rare cases, exposure to x-rays or other kinds of radiation may be a risk factor for developing myeloma^[3]. Environmental factors such as connections between multiple myeloma and exposure to pesticides, fertilizer, or Agent Orange have been noted^[5]. There is an increased risk of multiple myeloma in certain occupations due to exposure to aromatic hydrocarbon solvents^[4].

Diagnosis

Multiple myeloma is diagnosed based on blood or urine tests finding abnormal antibody proteins, bone marrow biopsy finding cancerous plasma cells, and medical imaging finding bone lesions^[4]. The diagnosis requires increased numbers of immature, abnormal, or atypical plasma cells in the bone marrow, a monoclonal protein in the serum or urine, or characteristic bone lesions^[3].

Sometimes a healthcare professional finds multiple myeloma during a blood test for another condition. Other times symptoms may lead to testing for multiple myeloma^[10].

Blood tests can show the M proteins made by myeloma cells in a blood sample. Blood tests might also find another protein myeloma cells make called beta-2-microglobulin. Other blood tests provide information about kidney function, blood cell counts, calcium levels, and uric acid levels^[10].

Urine tests can show M proteins in urine samples. In urine, these proteins are called Bence Jones proteins^[10].

Bone marrow tests include bone marrow biopsy and bone marrow aspiration, which are used to collect bone marrow samples for testing. Bone marrow has a solid and a liquid part. In a biopsy, a needle is used to collect a small amount of solid tissue. In aspiration, a needle is used to draw a sample of the fluid. The samples are typically taken from the hip bone. In the lab, tests look for myeloma cells and can provide more information about the cells, such as changes in their genetic material^[10].

Imaging tests can show bone problems linked with multiple myeloma. Tests may include X-ray, MRI scan, CT scan, or positron emission tomography (PET) scan^[10]. A skeletal survey is also part of the diagnostic workup^[15].

The diagnostic workup in a patient with suspected multiple myeloma should include a complete blood count with differential, serum chemistries, creatinine, lactate dehydrogenase, and beta-2-microglobulin tests, immunoglobulin studies, skeletal survey, and bone marrow evaluation^[15].

Treatment

Multiple myeloma treatment isn’t always needed right away. If the multiple myeloma is slow growing and isn’t causing symptoms, close watching might be the first step. This is sometimes called watchful waiting, where patients are carefully monitored through periodic testing and regular checkups^[2][13].

For people with multiple myeloma who need treatment, there are several ways to help control the disease. Initiation of chemotherapy and assessment of eligibility for autologous stem cell transplantation require referral to an oncologist. Patients should be evaluated to determine if they are a candidate for transplant, which includes assessing other health conditions and functional status^[15].

Chemotherapy is used for most myeloma patients with disease symptoms. The aim is to eliminate as many cancer cells as possible and bring about remission of the disease. A wide variety of drugs are used, including traditional chemotherapy agents, newer targeted drugs, and steroids. Most patients receive a combination of several drugs^[13].

Some patients can benefit from a stem cell transplant as follow-up treatment to high-dose chemotherapy. Transplant can also be used to treat recurrent myeloma^[13].

CAR T-cell therapy is a specialized immunotherapy that uses T-cells taken from your blood, reengineered in a lab to be more powerful cancer fighters, and infused back into your bloodstream where they target cancer cells^[13].

Radiation therapy can sometimes be used to treat a single plasmacytoma. Radiation can also help relieve pain caused by myeloma tumors in bone or other sites^[13].

Most patients with multiple myeloma will receive certain supportive treatments at some point. Bisphosphonate therapy, such as intravenous zoledronic acid or pamidronate, is recommended for all patients with multiple myeloma who are receiving treatment, regardless of the presence of bone lesions^[15].

Patients should receive thromboprophylaxis (treatment to prevent blood clots) when first diagnosed^[15]. Prophylaxis against infection is also important as part of treatment^[15].

Healthcare providers can’t cure multiple myeloma, but they can treat symptoms and related conditions. Often, they can slow its progress so patients can live longer^[5].

Complications

Multiple myeloma can lead to other medical issues. The abnormal proteins can damage organs in a condition called amyloidosis, or damage blood vessels in a condition called cryoglobulinemia^[5].

Bacterial infections are common complications, particularly pneumonia^[5]. Patients may experience broken bones because myeloma cells produce chemicals that stimulate bone breakdown and hinder bone replacement^[13].

High levels of calcium in the blood, called hypercalcemia, can occur^[5]. Nerve damage, known as peripheral neuropathy, is another possible complication^[5].

Some complications require emergency medical care. These include blood that’s too thick, called hyperviscosity syndrome, bones in the spine pressing against the spinal cord (myelopathy), and kidney failure^[5]. Myeloma cells also produce a protein that causes kidney damage, with symptoms including loss of appetite and nausea. About one-third of myeloma patients have impaired kidney function^[13].

Healthcare providers work with patients to manage or prevent these complications^[5].

Statistics

Multiple myeloma accounts for approximately 1.8% of all new cancer cases diagnosed in the United States each year^[7]. It represents about 1.6% of all cancer cases and approximately 10% of blood cancers in the United States^[15].

In 2015, an estimated 28,850 new cases of multiple myeloma were diagnosed in the United States, and the disease caused more than 11,000 deaths^[15]. Approximately 22,000 people in the U.S. are diagnosed with myeloma every year^[13].

Multiple myeloma occurs predominantly in the older population with a median age at diagnosis of about 70 years. Patients older than 65 years account for 85% of those diagnosed. Only 15% of patients diagnosed with multiple myeloma are younger than 65 years^[7][15].

It is slightly more commonly seen in males than females, with a ratio of 1.4 to 1^[7]. The disease is more common among men than women, and the risk of developing myeloma generally increases with age, with most patients diagnosed over 65^[13].

There is an increased incidence in African American and Black populations by as much as twofold compared to Whites^[7]. African Americans are twice as likely as Caucasians to develop the disease^[13].

The five-year survival rate in the USA is approximately 54%, with a life expectancy of about 6 years^[4].