Multiple myeloma is a blood cancer that occurs when one type of white blood cell called a lymphocyte develops abnormalities and grows out of control. Multiple myeloma and its related disorders affect a type of lymphocyte called plasma cells, also known as plasma B cells. Some plasma cell disorders are cancerous conditions, while others are not. In myeloma, abnormal versions of plasma cells are overproduced. They crowd out healthy cells and form tumors. Most tumors form in the bone marrow, causing pain, weakening the bones, and limiting the production of healthy blood cells. In some people, tumors form in soft tissues such as the throat, sinuses, lungs, or muscles.

Normal plasma cells secrete proteins called immunoglobulins — also known as Ig or antibodies — that recognize and destroy specific viruses and other threats. Antibodies produced by healthy plasma cells are an important part of the immune system. In plasma cell disorders, abnormal plasma cells secrete ineffective antibodies that do not provide protection, weakening the immune system and leaving the body unprotected from infection. In some cases, so many abnormal antibodies are present in the bloodstream that they interfere with blood flow and damage the kidneys.

Some types and stages of plasma cell disorders are mild and asymptomatic. They do not cause any symptoms, do not require treatment, and may never progress to cancer. Other types and stages can be life-threatening and must be treated urgently. Once someone has been diagnosed with a plasma cell disorder, they must be monitored regularly for progression.

Read more about how myeloma is diagnosed.

Types of Plasma Cell Disorders

Researchers believe that mild, asymptomatic types of plasma cell disorders always precede a cancer like multiple myeloma, although they are not caught and diagnosed in every person. However, the precancerous conditions only progress to cancer in a small fraction of people. Many people never progress from a milder disorder to multiple myeloma. Being diagnosed with a mild plasma cell disorder does not mean you will definitely develop multiple myeloma. Having a mild disorder means that, if your condition does progress, regular screenings will ensure that you receive a new diagnosis and treatment as early as possible.

Monoclonal Gammopathy of Undetermined Significance

Monoclonal gammopathy of undetermined significance (MGUS) is diagnosed when abnormal antibodies — called monoclonal proteins or M proteins — are found in the blood, usually during blood tests for unrelated conditions. MGUS is not a cancerous condition and does not involve a tumor. People with MGUS have a 1 percent chance each year of their condition progressing to multiple myeloma. People may also progress to other more serious plasma cell disorders, like smoldering multiple myeloma, or to conditions related to abnormal antibodies, like amyloidosis or light chain deposition disease. MGUS is asymptomatic.

The standard recommendation is for watchful waiting instead of treatment for MGUS. People diagnosed with MGUS may undergo blood and urine testing once every six or 12 months to monitor for progression. Doctors classify MGUS as having a low, intermediate, or high risk of progressing to myeloma. However, risk levels can get worse over time. Doctors now recommend that everyone with MGUS, including those with few risk factors, get screened regularly for myeloma.

If routine monitoring shows evidence of progression, your doctor may recommend beginning treatment. Those diagnosed with both MGUS and osteoporosis may take a bisphosphonate medication, such as Aredia (pamidronate) or Zometa (zoledronic acid), to help maintain bone mineral density.

Subtypes of MGUS include IgM MGUS, non-IgM MGUS, and light chain MGUS.

Read more about MGUS.

Smoldering Multiple Myeloma

Like MGUS, smoldering multiple myeloma (SMM) is a disorder involving abnormal antibodies in the blood with no myeloma signs or symptoms. Some doctors are now calling this condition asymptomatic myeloma. In some people, SMM progresses to multiple myeloma. People with SMM have a higher risk for disease progression than those with MGUS, although this risk decreases over time:

• For the first five years after being diagnosed with SMM, a person has a 10 percent risk of developing myeloma each year.
• For the next five years, a person has a 3 percent chance per year of developing myeloma.
• Ten years or more after SMM diagnosis, a person has a 1 percent chance of developing myeloma each year.

Rarely, when the abnormal plasma cells of someone with SMM are tested, they show specific genetic characteristics that carry a risk of progression much higher than the average. Some people have a higher burden of abnormal cells than others, as measured by blood tests and bone marrow biopsy. In this subset of high-risk SMM cases, doctors may recommend beginning treatment to delay the progression to cancer. Ongoing clinical trials are helping doctors learn more about which treatments can best improve outcomes for people with SMM.

Researchers believe either MGUS or SMM precede all cases of multiple myeloma.

Read more about smoldering multiple myeloma.

Solitary Plasmacytoma

If one cancerous tumor formed by abnormal plasma cells is present, it is known as a solitary plasmacytoma. Solitary plasmacytomas most frequently develop in bone, where they are known as solitary bone plasmacytomas or solitary medullary plasmacytomas. Symptoms of solitary bone plasmacytoma depend on where the tumor is located, but it may cause pain, fracture, or compression of the spinal cord. Some cases of solitary bone plasmacytoma are cured with radiation therapy. Between 50 percent and 70 percent of people diagnosed with solitary bone plasmacytoma progress to multiple myeloma within a few years.

Extramedullary Plasmacytoma

A plasmacytoma may also grow in soft tissues such as the nose, throat, lung, bladder, or muscle. A plasmacytoma that occurs in soft tissue is called an extramedullary plasmacytoma. About 80 percent of solitary extramedullary plasmacytomas occur in the upper respiratory tract — in the nose, sinuses, or upper throat.

Signs and symptoms of extramedullary plasmacytoma depend on the location, but may include pain or obstruction — for instance, an obstruction of the respiratory, urinary, or digestive tract. A solitary extramedullary plasmacytoma has a lower risk of progressing to multiple myeloma — approximately 8 percent. Extramedullary plasmacytomas may also occur in addition to bone tumors in those with multiple myeloma.

Localized Myeloma

In cases of a plasmacytoma that is spreading to just a few neighboring sites, the term localized myeloma may be used. Localized myeloma differs from multiple myeloma because the cancer is still confined to one area of the body rather than widespread.

Multiple Myeloma

Multiple myeloma is diagnosed when cancerous plasma cells cause widespread problems throughout the body. Bones are the most common site for cancer cells to build up, but tumors in soft tissue (extramedullary plasmacytomas) can also develop. Signs and symptoms of multiple myeloma can be severe and may include:

• Bone pain, weakness, or breaks
• Spinal cord compression (weakened bones in the spine pressing on nerves), which causes back pain and leg numbness or weakness
• Anemia (low red blood cell levels), which causes fatigue and weakness
• Leukopenia (low numbers of white blood cells), which leads to frequent infections
• Thrombocytopenia (low platelet counts), which causes bleeding problems
• Hypercalcemia (high calcium levels), which causes dehydration, extreme thirst, frequent urination, constipation, abdominal pain, tiredness, and confusion
• Kidney damage or failure, which leads to shortness of breath, itching, and swelling of the legs

Myeloma cells produce large amounts of abnormal antibodies. Doctors sometimes classify cases of multiple myeloma into subtypes based on which types of antibodies are being made. Myeloma may be classified as IgG, IgA, IgD, IgE, or IgM. Rarely, myeloma cells don’t make any (or very few) antibodies. Doctors call this non-secretory myeloma.

Multiple myeloma is a dangerous plasma cell disorder. Multiple myeloma currently is not curable in most cases, and it can be fatal. However, it is highly treatable. New multiple myeloma treatment options can keep the condition under control for a long time.

When multiple myeloma is diagnosed, doctors assign it a stage. The stage of myeloma reflects how far the myeloma has progressed. Read more about stages of multiple myeloma.

Relapsed Myeloma

Multiple myeloma that has returned after a previous effective treatment is known as relapsed myeloma. Relapsed myeloma may be treated with the same treatments that were effective before, or doctors may recommend different treatments after a relapse.

Refractory Myeloma

Multiple myeloma that has progressed despite treatment is called refractory myeloma. Refractory myeloma is by definition more difficult to treat. Some people with refractory myeloma participate in a clinical trial for a chance to access experimental cancer treatments.

Light Chain Myeloma

In most cases of multiple myeloma, cancerous plasma cells secrete abnormal antibodies. In about 15 percent of cases, myeloma cells secrete only fragments of antibodies known as light chain proteins or Bence-Jones proteins. This is known as light chain myeloma. Light chain myeloma can be further subtyped by the type of light chain protein as either kappa light chain myeloma or lambda light chain myeloma. People with light chain myeloma are significantly more likely to experience kidney failure than those with non-light chain myeloma.

Read more about light chain myeloma.

AL Amyloidosis

AL amyloidosis is another condition that affects light chain proteins. AL amyloidosis is not cancer, and people with this condition don’t have high levels of plasma cells. In AL amyloidosis, plasma cells make high levels of abnormal light chain protein. The proteins stick together, forming clumps called amyloid deposits. The deposits build up in tissues throughout the body and cause organ damage. People with AL amyloidosis may have decreased kidney function, heart damage, digestive system problems, and neuropathy. AL amyloidosis is treated with many of the same treatments that are used for multiple myeloma.

Condition Guide

• Multiple Myeloma — An Overview
• Symptoms of Multiple Myeloma
• Multiple Myeloma — The Path to Diagnosis
• Stages of Multiple Myeloma
• Treatments for Myeloma
• What Causes Multiple Myeloma?
• Comorbidities and Complications of Multiple Myeloma