Multiple myeloma is a type of blood cancer that occurs when lymphocytes (white blood cells) called plasma cells begin to grow in a rapid, uncontrolled way. Abnormal plasma 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, malignant plasma cells secrete abnormal proteins that can damage the kidneys and other organs.
In the human body, 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 start 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 change, it can lead to cancer. Myeloma cancer cells divide at a faster rate without regulation or order, becoming more and more mutated. Other cancers may grow at a slower rate, but do not stop growing. When these disordered cells begin to invade nearby tissues or break off and migrate to other locations, they are called cancer.
There are many types of disorders that can affect plasma cells. Some types and stages of plasma cell disorders are mild and asymptomatic. They do not cause any symptoms and do not require treatment, but they may progress to multiple myeloma in a small fraction of people. More severe plasma cell disorders, including myeloma, 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. He was treating a 39-year-old named Sarah Newbury who had developed severe bone pain and multiple bone fractures. Newbury died after four years, despite treatment with rhubarb pills and infusions of orange peel. Autopsy revealed Newbury’s 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 Thomas McBean, who experienced a series of unusual fractures. McBean did not respond to traditional treatment with leeches, but he improved for a time after receiving preparations of steel and quinine. After McBean died, an autopsy showed bone lesions containing similar cells as those found in Newbury.
Before McBean died, Watson sent samples of his 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 person 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 similar cases. By 1928, when American pathologists Charles Geschickter and Murray Copeland published an overview on more than 400 case reports of multiple myeloma, the modern term was in general use.
In the 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 myeloma cells. These abnormal proteins, also called monoclonal proteins, 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 first tested as an antimyeloma medication.
The first two decades of the 21st century brought a revolutionary number of effective new treatment options for multiple myeloma. Zometa (zoledronic acid) was introduced in 2002 to help prevent fractures. Anticancer drug Velcade (bortezomib) followed in 2003. Revlimid (lenalidomide) was approved by the U.S. Food and Drug Administration for myeloma treatment in 2006. Kyprolis (carfilzomib) was approved in 2012, and Pomalyst (pomalidomide) 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 (ISS). The original ISS considered several factors, including age, blood levels of certain proteins, and platelet count, to determine risk for progression. In 2015, the International Myeloma Working Group introduced a Revised International Staging System (R-ISS) that also took into account genetic traits found in cancer cells and levels of the enzyme LDH.
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 2021, nearly 35,000 people will be diagnosed with multiple myeloma in the United States. The average risk for any American to develop myeloma during their lifetime is 0.8 percent. Other factors may increase or decrease an individual’s risk for myeloma. Age is one of the most important factors in myeloma risk. Less than 1 percent of myeloma cases are diagnosed in people under 35, and myeloma is most prevalent in people over 65. In the United States, Black people are more than twice as likely to develop myeloma as white Americans, according to Cancer.Net. Men are slightly more likely than women to develop myeloma, according to Cancer Research UK.
Monoclonal gammopathy of undetermined significance (MGUS) — a mild, asymptomatic plasma cell disorder — is more common than multiple myeloma. MGUS is estimated to occur in about 2.3 percent of white Americans, 3.7 percent of African Americans, and 1.8 percent of Hispanic 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. Doctors use various test findings to diagnose myeloma and related disorders, including:
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 they experience problems with bone fractures or kidney dysfunction. Early stage myeloma that doesn’t cause symptoms is known as smoldering multiple myeloma (SMM). SMM may be detected during blood tests for unrelated health issues.
Read more about multiple myeloma symptoms.
Myeloma treatments fall into a few main categories:
Most cases of myeloma are treated with chemotherapy followed by autologous stem cell transplant. Supportive treatments can help reduce treatment side effects and improve quality of life. 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:
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 from 2011 to 2017 indicates that 55.6 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 percent of cancer deaths in the United States.
In most cases, multiple myeloma is not curable. Stem cell transplantation from a donor — an allogeneic stem cell transplant — can be curative in rare cases, but it is fraught with risks and complications. Newer treatments, including new drugs and CAR T-cell therapy, may produce cures, but this possibility is still unknown.
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.
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