What is Multiple Myeloma?

Multiple myeloma is a type of blood cancer that affects plasma cells. In multiple myeloma, malignant plasma cells accumulate in the bone marrow (the soft, spongy tissue at the center of your bones), crowding out the normal plasma cells that help fight infection. These malignant plasma cells then produce an abnormal antibody called M protein, which offers no benefit to the body and may cause tumors, kidney damage, bone destruction, and impaired immune function. The hallmark characteristic of multiple myeloma is a high level of M protein in the blood.

Multiple myeloma typically displays the most activity in bone marrow, which includes the marrow in the spine, pelvic bones, ribs, shoulders, and hips.

Though it is rarely curable, multiple myeloma is a highly manageable disease that has seen rapid medical advancement over the past decade. With the creation of the Multiple Myeloma Research Foundation (MMRF) and the push for advancement of multiple myeloma therapies, ten new drugs have been approved in the time it typically takes to obtain a single drug approval. The MMRF continues to investigate and fund the most promising treatments for multiple myeloma.

Steps to take after a multiple myeloma diagnosis

When you’re diagnosed with a condition like multiple myeloma, it’s important that you be an advocate for your care. Here are some things you can do to help ensure the best possible outcome for you:

1. Find the right treatment center and the right doctor.
2. Get the right diagnostic tests, and have your genome sequenced.
3. Work with your doctor to determine the right treatment plan, including any clinical trials.
4. Share your data with communities and registries to help advance multiple myeloma research.

Learn more about multiple myeloma diagnosis:


Multiple myeloma basics

What do plasma cells do?

Plasma cells are a type of white blood cell found within the bone marrow. Normally, plasma cells make up about 5% of all cells in the bone marrow. They are part of the immune system, playing an important role in combating infection by producing disease-fighting proteins called immunoglobulins, or antibodies.

Plasma cells develop from a type of white blood cell called B cells when foreign substances (antigens), such as bacteria, enter the body. In response to invasion by antigens, groups of plasma cells produce antibodies to fight off disease and infection. Each plasma cell develops in response to a particular antigen within the body and produces antibodies specific to it. As a result, many different antibodies are produced in the body.

What happens to plasma cells in multiple myeloma?

In multiple myeloma, healthy plasma cells transform into malignant plasma cells (myeloma cells) through a complex, multistep process. Myeloma cells produce large amounts of a single abnormal antibody called M protein. Unlike normal antibodies, M protein does not fight infection.

The growing number of malignant plasma cells themselves crowd out other healthy blood cells in the bone marrow, resulting in decreased numbers of red blood cells, white blood cells, and platelets.

In healthy bone marrow, B cells, a type of white blood cell, develop into antibody-producing plasma cells when antigens enter the body. In multiple myeloma, DNA damage to B cells transforms normal plasma cells into malignant multiple myeloma cells. The cancerous cells multiply, leaving less space in the bone marrow for normal blood cells and producing large quantities of M protein.

How does this affect the body?

Due to the reduced number of healthy cells, common symptoms of multiple myeloma are anemia, excessive bleeding, and decreased ability to fight infection. The buildup of M protein in the blood and urine can cause damage to the kidneys and other organs. Furthermore, the myeloma tumors can cause damage and pain to bones. Most patients diagnosed with multiple myeloma have osteolytic lesions, which are weakened spots on bones. This bone destruction increases the risk of fractures. It can also lead to a serious condition called hypercalcemia (increased levels of calcium in the blood).

Adapted with permission from DeVita VT Jr, Hellman S, Rosenberg SA, eds. Cancer: Principles and Practice of Oncology. 5th ed. Philadelphia, PA: Lippincott Williams and Wilkins; 1997.


Blood cancers and plasma cell neoplasms

Blood cancers

Blood cancers (also called “hematologic malignancies”) such as multiple myeloma affect the function and production of blood cells. In most blood cancers, normal blood cell development is interrupted by uncontrolled growth of abnormal blood cells. The abnormal blood cells can stop blood from fighting off infection or preventing uncontrolled bleeding.

Different types of blood cancer affect different components of the blood. Multiple myeloma affects the plasma cells in bone marrow, causing them to form tumors. There are two main types of blood cancer besides multiple myeloma: leukemia and lymphoma.

Leukemia

Leukemia is a blood cancer in both the bone marrow and blood itself. Lymphocytic leukemia involves overproduction of a type of white blood cell called lymphocytes, while myelogenous leukemia involves overproduction of granulocytes, another type of white blood cell. Over time, leukemia cells crowd out normal blood cells, leading to serious bleeding and infection.

Lymphoma

Lymphoma is a blood cancer that develops in the lymphatic system. The lymphatic system is made up of groups of lymph nodes that keep body fluids free from infection. The blood cancer may spread from one group of lymph nodes to another in order (Hodgkin lymphoma) or randomly (non-Hodgkin lymphoma).

Plasma cell neoplasms

Multiple myeloma is not the only disease that causes abnormal growth of plasma cells in the bone marrow. Collectively, diseases that do this are called “plasma cell neoplasms.”

Normally, plasma cells make antibodies that fight infection. Plasma cell neoplasms are seen when plasma cells grow uncontrollably and make antibody proteins called M proteins that do not help fight infection. These M proteins build up in the blood and bone marrow, leading to thickened blood or damaged kidneys. In multiple myeloma, these abnormal plasma cells grow in the bone marrow and form tumors.

Plasma cell leukemia is a cancer where abnormal plasma cells are found circulating in the blood and not in the bone marrow. Primary plasma cell leukemia occurs in patients with no previous history of blood cancer; secondary plasma cell leukemia occurs in patients with multiple myeloma whose myeloma cells migrate to the bloodstream and circulate throughout the body. Plasma cell leukemia is a rare condition associated with an aggressive course. Newer treatment regimens that include proteasome inhibitors (like Velcade or Kyprolis) and immunomodulatory agents (like Revlimid or Pomalyst) have improved survival for these patients, but outcome s remain poor in this challenging disease.

Other types of plasma cell neoplasm include solitary plasmacytoma and monoclonal gammopathy of undetermined significance (MGUS). These two conditions are not multiple myeloma, but may progress and become multiple myeloma. For this reason, people who have either of these conditions are closely monitored by their doctors.



Causes and risk factors

What causes multiple myeloma?

The exact cause of multiple myeloma has not yet been identified. In the past several decades, however, researchers have made several advancements in understanding how multiple myeloma develops.

Generally speaking, cancer is caused by genetic mutations. Genes are basically the “instructions”—made of DNA—that your cells use to assemble proteins, or the “workers” of the cell. The human genome is made up of approximately 30,000 genes, located along 23 chromosomes, that can be read in different ways to assemble about three proteins each.

Every time a cell divides, all 23 chromosomes must be copied. Genetic mutations (alterations) may occur during this process—and some mutations can have a drastic impact on the protein that is made from that gene. Although the body produces certain proteins dedicated to making sure the genetic code is correct, errors that cannot be fully corrected sometimes occur. When this happens, the cell begins to rapidly grow and divide, ultimately causing cancer.

Specific mutations have been identified as genetic risk factors for both developing multiple myeloma and likelihood of early relapse. For instance, chromosome 13 is deleted in multiple myeloma cells in about half of all cases. Additionally, chromosomal translocations (where pieces of a chromosome are swapped, turning some genes on when they should be off and vice versa) are observed in about 40% of multiple myeloma cases.

Despite these known genetic risk factors, multiple myeloma, like all cancers, is heterogeneous, meaning each case is unique. The genetic mutations that cause multiple myeloma in one person are often different from those that cause it in another. In fact, MMRF initiatives such as the Multiple Myeloma Immunology Initiative and the MMRF CoMMpass Study have shown that multiple myeloma has at least 12 different genetic subtypes, rather than a single genetic makeup. For this reason, the MMRF is committed to advancing precision medicine, the practice of tailoring treatment to the distinct genetics of the cancer in an individual patient.

Is multiple myeloma hereditary?

Genetic mutations can be either inherited (something you’re born with) or acquired over time. When a disease is caused by inherited genetic mutations, it is considered to be hereditary, meaning that it can be passed down from parent to child through the genes.

Although there is a very slight increase in risk for multiple myeloma for first-degree relatives (parents or siblings) of people with multiple myeloma, it is not thought to be a hereditary disease. Research indicates that it’s very uncommon for more than one member of a family to have multiple myeloma.

If you have multiple myeloma, it’s most likely that your plasma cells acquired enough mutations during your lifetime to transform from healthy cells into cancer cells.

What are the risk factors for developing multiple myeloma?

In addition to the genetic risk factors described above, there are other known risk factors for multiple myeloma. The most significant risk factor is age, as 96% of cases are diagnosed in people over 45 years of age, and more than 63% are diagnosed in people over the age of 65 years. Thus, it is thought that susceptibility to multiple myeloma may increase with the aging process.

African-American race and male gender are also correlated with an increased incidence of multiple myeloma. Occupational exposure to asbestos, benzene, pesticides, or chemicals from rubber manufacturing has been associated with an increased likelihood of developing multiple myeloma. A decline in the immune system, exposure to radiation, and previous diagnosis of MGUS are also risk factors.

Keep in mind that these risk factors only slightly increase your chance of developing multiple myeloma; they have not been proven to cause multiple myeloma. In fact, a recent study demonstrated that most cancer is caused by random mutations.


Multiple myeloma classifications

Knowing the classification of your disease is very important in deciding when it is appropriate to begin treatment. Classification also plays an important role in determining the stage of multiple myeloma.

1. Monoclonal gammopathy of undetermined significance (MGUS)

MGUS is a plasma cell neoplasm diagnosed when a small amount of M protein is detected in the blood, but no other criteria for a solitary plasmacytoma or multiple myeloma diagnosis (such as a tumor, multiple lesions, or symptoms) are present. MGUS occurs in about 1% of the general population.

MGUS usually does not cause any problems or require treatment, but in rare cases (1%-2%), it can develop into multiple myeloma. People living with MGUS receive regular checkups to ensure that it does not progress.

2. Solitary (or isolated) plasmacytoma

A single group of malignant myeloma cells (rather than multiple lesions, as in multiple myeloma) is called a “solitary plasmacytoma.” This mass of cells can grow inside or outside of bone. An “extramedullary plasmacytoma” is one that grows outside the bone, while an “isolated plasmacytoma of the bone” is one that grows within the bone. Isolated plasmacytoma of the bone can affect any bone, but tends to occur most frequently in the bones along the spinal column.

Solitary plasmacytoma within the bone is normally diagnosed by a biopsy that reveals abnormal plasma cells. With a solitary plasmacytoma, bone imaging (X-rays, positron-emission tomography [PET] scan, or magnetic resonance imaging [MRI]) detects only a single lesion. Blood tests show no anemia or high calcium levels, and kidney function is normal.

Solitary plasmacytoma is rare, making up only 5% of plasma cell disorders. It is commonly treated with radiation therapy and rarely requires surgery. Prognosis with radiation alone is usually excellent, but there is a risk that a solitary plasmacytoma could recur and progress to multiple myeloma. People with a solitary plasmacytoma will have long-term follow-up appointments to ensure they remain in remission.

3. Smoldering (or asymptomatic) multiple myeloma

Smoldering multiple myeloma (SMM) is a precancerous form of multiple myeloma that typically accounts for about 15% of newly diagnosed multiple myeloma cases. It is diagnosed when low levels of M protein are found in the blood and a slightly increased number of plasma cells are found in the bone marrow. Many patients with SMM are asymptomatic, but some experience modest symptoms, such as mild anemia or a few small bone lesions .

Many—but not all—patients with SMM progress to multiple myeloma. The risk of progression is about 10% each year for the first 5 years following diagnosis, 3% between years 5 and 10, and about 1% in subsequent years.

The commonly accepted approach to SMM used to be “watchful waiting.” Now, however, many studies are showing the benefit of earlier treatment, particularly for people with SMM that has genetic traits that put them at higher risk for disease progression to full-blown multiple myeloma. Early intervention has demonstrated success in preventing multiple myeloma development. Further studies are under way, and a main initiative of the MMRF is to ensure that each individual receives the best treatment available.

4. Multiple myeloma

Multiple myeloma is a type of cancer that affects plasma cells in the blood, causing them to grow and divide. The “multiple” in multiple myeloma indicates that there are multiple tumors in different areas of the bone(s). More than 90% of individuals diagnosed with multiple myeloma have multiple tumors at the time of diagnosis.

Characteristics of multiple myeloma include elevated levels of M protein and plasma cells in the serum and/or urine, a percentage of plasma cells in the bone marrow over 30%, anemia, renal failure, hypercalcemia, and osteolytic lesions.

When present, symptoms of multiple myeloma may be vague and similar to those of other conditions. Some multiple myeloma symptoms are more common than others, and less common symptoms may be the result of complications that may occur.

Management of multiple myeloma includes immediate treatment with myeloma drugs, bisphosphonates for patients with bone loss, and options for clinical trials.

Depending on the classification of your disease, as well as other factors, you may not have to receive treatment immediately. In some cases, postponing therapy may help avoid unnecessary side effects and the risk of complications associated with chemotherapy, and it may also delay development of resistance to chemotherapy. Even if you don’t receive disease-directed therapy right away, you may still receive supportive care to treat symptoms or complications. Work with your healthcare team to determine the right treatment approach for you.