Multiple myeloma is a type of cancer that occurs when lymphocytes (white blood cells) called plasma B cells begin to grow in a rapid, uncontrolled way. Abnormal plasma B cells can form tumors in bone marrow or soft tissue, causing pain and weakening bones. By crowding out healthy bone marrow, multiple myeloma causes a dangerous drop in the number of healthy blood cells produced in the marrow. In some people with multiple myeloma, cancerous plasma B cells secrete abnormal proteins that can damage the kidneys or interfere with blood flow.
Normal cells divide in a regular, ordered fashion to form new cells that are exact copies to replace old ones. Certain genes in each cell are responsible for telling cells when to divide and when to stop dividing. Other genes identify and fix problems in incorrectly copied DNA or cause cells with bad DNA to self-destruct rather than keep multiplying. If a genetic mutation causes one or more of these genes to turn off in some cells, they can divide at a faster rate without regulation or order, becoming more and more mutated. When these disordered cells begin to invade nearby tissues or break off and migrate to other locations, they are called cancer.
In some types of multiple myeloma, one variety of white blood cell — a lymphocyte — is overproduced. For this reason, these conditions are known as lymphoproliferative disorders. Some types and stages of lymphoproliferative disorders are mild and asymptomatic; they do not cause any symptoms, do not require treatment, and only progress to cancer in a small fraction of people. Other types and stages can be life-threatening and must be treated urgently.
Although multiple myeloma has likely existed since ancient times, English physician Samuel Solly published the first well-documented case of multiple myeloma in 1844. His patient, a 39-year-old woman named Sarah Newbury, had developed fatigue and multiple bone fractures. She died after four years, despite treatment with rhubarb pills and infusions of orange peel. Autopsy revealed her bone marrow had been replaced with a red substance that contained unusual cells. Solly referred to Newbury’s condition as ”mollities ossium,” a Latin phrase meaning “softening of the bones.”
The following year, London physician Thomas Watson treated a patient named Thomas McBean, who experienced a series of unusual fractures. The patient did not respond to traditional treatment with leeches, but improved for a time after receiving preparations of steel and quinine. After the patient died, an autopsy showed bone lesions containing similar cells as those found in Sarah Newbury.
Before McBean died, Dr. Watson sent samples of McBean’s urine to English pathologist Henry Bence Jones for analysis. Bence Jones found elevated levels of protein in the urine that he connected to the softening of the bones. Bence Jones recommended that every patient with these symptoms have their urine tested for the protein. Today, Bence-Jones proteins (also known as M proteins or light chains) are part of the diagnostic criteria for multiple myeloma.
In the late 1880s, multiple myeloma became known as Kahler’s disease after Prague physician Otto Kahler documented a case involving a patient with bone pain, spinal deformities, loss of height, pneumonia, and anemia (low levels of red blood cells). Although the term “multiple myeloma” had been introduced by Ukrainian physician J. von Rustizky in 1873, the report in which he mentioned the term lacked drawings and was not immediately connected to other similar cases. By 1928, when American pathologists Charles Geschickter and Murray Copeland published an overview on 400 case reports of multiple myeloma, the modern term was in general use.
In the 1950s and 1960s, treatments such as Melphalan (known by its brand name Alkeran) and corticosteroids like Prednisone were first used in cases of multiple myeloma. During this period, Swedish physician Jan Waldenström identified abnormal antibodies (proteins used by the immune system to fight infection) produced by plasma B cells in people with multiple myeloma. Monoclonal antibodies are a vital component in the diagnosis of myeloma and related disorders to this day.
First introduced in the 1970s, the Durie-Salmon staging system is still used by some doctors to stage multiple myeloma. During this decade, doctors began combining different medications into more effective regimens for multiple myeloma treatment.
During the 1980s, autologous stem cell transplants and allogeneic stem cell transplants began to be used to treat multiple myeloma. In the 1990s, Thalidomide (known by its brand name Thalomid) was developed as an anti-myeloma medication.
The first two decades of the 21st century brought a revolutionary number of effective new treatments for multiple myeloma. Zometa (Zoledronic acid) was introduced in 2002 to help prevent fractures. Anti-myeloma drug Velcade (Bortezomib) followed in 2003. Kyprolis (Carfilzomib) was approved by the U.S. Food and Drug Administration (FDA) in 2012, and Pomalyst (Pomalidomide) and Revlimid (Lenalidomide) followed in 2013. Darzalex (Daratumumab), Empliciti (Elotuzumab), Farydak (Panobinostat), and Ninlaro (Ixazomib) were all approved in 2015.
The early 2000s also brought a new wave in multiple myeloma staging: the International Staging System. Many doctors consider the ISS to be a more accurate assessment of the risk for multiple myeloma progression since it involves analyzing the cancer cells for genetic traits that carry a high risk for progression.
Today, hundreds of clinical trials around the world are actively testing new medications, new combinations of medications, and better procedures for treating — and hopefully curing — multiple myeloma.
The National Cancer Institute estimates that in 2015, there were more than 124,000 people living with multiple myeloma in the United States. The average risk for any American to develop myeloma during their lifetime is 1 in 132, or 0.76 percent. Other factors may increase or decrease an individual’s risk for myeloma. Age is the most important factor in myeloma risk, which increases as people get older. Less than 1 percent of myeloma cases are diagnosed in people under 35. Myeloma is most prevalent in people over 65. In the U.S., African Americans are more than twice as likely to develop myeloma as white Americans. Men are about 40 percent more likely than women to develop myeloma.
Monoclonal gammopathy of undetermined significance (MGUS), a mild, asymptomatic lymphoproliferative disorder, is more common than multiple myeloma. MGUS is estimated to occur in about 3.2 percent of white Americans and at about twice that rate in African Americans. Each year, about 1 percent of people with MGUS progress to multiple myeloma.
Read more about risk factors for multiple myeloma.
Multiple myeloma is diagnosed based on the results of clinical tests. Test findings such as abnormal cells in the bone marrow, abnormal proteins in the blood, kidney dysfunction, low levels of red blood cells, and imaging scans that show tumors are evidence doctors use to diagnose myeloma and related disorders.
Learn more about how multiple myeloma is diagnosed.
For some people, early symptoms of multiple myeloma can include back pain, pain in the bones, fatigue, nausea, or a severe infection. Other people with myeloma may not notice that anything is wrong until a bone fractures or kidney function is affected. For about 30 percent of people, multiple myeloma is asymptomatic (without symptoms) at diagnosis. In these cases, myeloma is detected during blood tests for unrelated health issues.
Read more about multiple myeloma symptoms.
Myeloma treatments fall into five main categories: chemotherapy and other antimyeloma medications, radiation therapy, stem cell transplants, surgeries, and supportive treatments. Most cases of myeloma are treated with chemotherapy followed by autologous stem cell transplant. Healthy lifestyle choices, such as a nutritious diet and regular exercise, can help those with myeloma feel their best and recover from treatment more readily.
Learn more about treatments for multiple myeloma.
The prognosis for an individual case of multiple myeloma depends on many factors, including your age and general health, the stage at which the cancer is diagnosed, which treatments are used, and how the myeloma responds to treatment. Longevity of those diagnosed with multiple myeloma has been increasing since the introduction of new medications and treatment regimens. Some medications are so new that long-term data is not yet available. Data collected between 2008 to 2014 indicates that 50.7 percent of people with multiple myeloma were still alive five years after their diagnosis. According to the National Cancer Institute, multiple myeloma accounts for 2.1 percent of cancer deaths in the United States.
In most cases, multiple myeloma is not curable. The majority of people with multiple myeloma experience a relapse at some point. The effectiveness of new medications and regimens means that for many people, myeloma is a chronic condition that can be managed with treatment. Survival rates for people with multiple myeloma continue to improve.