Multiple myeloma

ALSO KNOWN AS: MM, myeloma, plasma cell myeloma, cancer of the bone marrow

RELATED CONDITIONS: Multiple gammopathy of undetermined significance (MGUS), smoldering myeloma, indolent myeloma

DEFINITION: Multiple myeloma is a cancer involving several clusters of cancerous plasma cells (a type of white blood cell found in the bone marrow that produces immunoglobulins to fight infection) in various bones of the body.

Risk factors: No one is sure what causes multiple myeloma. People who have been exposed to agricultural and other chemicals such as Agent Orange, some types of radiation, and some viruses appear to be more susceptible to multiple myeloma. People with multiple myeloma are usually diagnosed in their fifties and sixties. The disease is identified more often in men than in women, and it is more often in Black Americans than in members of other ethnic groups. Scientists have not been able to associate multiple myeloma with a genetic trait, but research suggests that chromosome 13 may be incomplete or entirely missing in myeloma cells.

Patients with a condition known as multiple gammopathy of undetermined significance (MGUS) have a relatively large amount of immunoglobulin protein (the M-protein) present in their blood. MGUS itself is benign, but about 1 percent of individuals with the condition eventually develop multiple myeloma. Patients with smoldering or indolent myeloma, often a precursor disease, exhibit higher levels of calcium and kidney dysfunction, anemia, and bone disease.

Etiology and the disease process: Multiple myeloma occurs when abnormal plasma cells in the bone marrow multiply, accumulate, and overtake the healthy plasma cells. As the plasma cells circulate in the bloodstream, they often settle in other bones and interfere with the body’s ability to produce normal antibodies, which leads to difficulty fighting infections.

Incidence: Approximately 157,561 Americans have multiple myeloma. The American Cancer Society estimated that there were approximately 35,740 new cases of multiple myeloma in 2023, with approximately 12,590 deaths. Furthermore, it was estimated that the lifetime risk of getting multiple myeloma in one's lifetime was 1 in 103 for men living in the United States and 1 in 131 for women.

Symptoms: The early stages of multiple myeloma may be uneventful and indistinct from other maladies. Multiple myeloma is often marked by successive infections, weight loss, fatigue or weakness, broken bones, or bone pain, most commonly in the ribs or back.

Screening and diagnosis: Kidney problems are often the first indication that something is wrong. High levels of protein in the blood can cause kidney damage, and high levels of calcium may indicate the beginning or presence of kidney problems. Symptoms of kidney problems include greater thirst and urine production, a loss of appetite, fatigue, muscle weakness, restlessness, confusion or an inability to concentrate, constipation, and nausea and vomiting. An accurate diagnosis requires consideration of the patient’s history and symptoms, a complete physical, and an evaluation of laboratory results.

A diagnosis of multiple myeloma requires blood tests to determine the amount of calcium and plasma cells in the blood and the patient’s degree of anemia. Technologists will look for the presence of M-protein, beta-2 microglobulin (β2M), and other proteins in a blood sample and for the presence of the Bence-Jones protein (a type of M-protein) in the urine. Additional testing will include imaging studies, X-rays, computed tomography (CT) scans, or magnetic resonance imaging (MRI) studies to examine whether bone cavities exist and whether they might be caused by a tumor. This is followed by taking a tissue sample from a large bone to examine whether myeloma cells are present in the marrow.

Most clinicians use the International Staging System to categorize multiple myeloma using the following criteria:

• • Stage I: Serum β2M less than 3.5 milligrams/deciliter (mg/dl) and serum albumin greater than or equal to 3.5 grams/deciliter (g/dl)
• • Stage II: Serum β2M less than 3.5 mg/dl and albumin less than 3.5 g/dl or serum β2M 3.5 to 5.5 mg/dl
• • Stage III: Serum β2M greater than 5.5 mg/dl

Higher serum β2M levels and lower serum albumin levels usually indicate active or advanced disease. Increased values of C-reactive protein and serum lactate dehydrogenase also may indicate active disease.

Treatment and therapy: There is no cure for multiple myeloma, but several treatment options exist, and new options are being developed. The aim of most therapies is to ease a patient’s symptoms and slow the progression of disease, relieve pain and discomfort, and stabilize the immune system and metabolic functions. Various combination therapies are being used to combat multiple myeloma. These include dexamethasone, either alone or in combination with thalidomide or melphalan; melphalan plus prednisone; a combination drug known as VAD (vincristine/doxorubicin/dexamethasone); and bortezomib, either alone or in combination with other drugs such as dexamethasone, lenalidomide, or doxorubicin liposomal (Doxil). Additional therapies include the use of cyclophosphamide or etoposide. Each drug combination has advantages and disadvantages; not all drug combinations work well in all patients. Some patients have had extremely good results using these drugs, and many have experienced disease remission.

In the 2020s, new treatments for multiple myeloma using CAR-T Cell Therapy showed promise. These therapies use genetically modified immune cells from the patient to fight cancer. In 2021 and 2022, the US Food and Drug Administration (FDA) approved idecabtagene vicleucel and ciltacabtagene autoleucel, which targeted a protein often found in multiple myeloma cells. In 2023, the FDA approved talquetamab and elranatamab as bispecific antibodies that could be used in immunotherapies that target multiple myeloma cells. 

Prognosis, prevention, and outcomes: Most patients live many years after a diagnosis of multiple myeloma. Physicians may offer treatments for bone pain, infections, anemia, and fatigue or weakness, which are considered to be the most common body effects associated with multiple myeloma.

Bibliography

Anderson, Kenneth C., and Irene Ghobrial, eds. Multiple Myeloma. New York: Informa Healthcare, 2007.

Brian, G., M., et al. “International Uniform Response Criteria for Multiple Myeloma.” Leukemia, vol. 20.9, 2006, p. 1467.

Dominik, D., et al. “Multiple Myeloma: A Review of the Epidemiologic Literature.” International Journal of Cancer, vol. 120.12, 2007, pp. 40–61.

“FDA Approves Two New Treatments for Heavily Pretreated Multiple Myeloma.” Leukemia & Lymphoma Society, 16 Aug. 2023, www.lls.org/news/fda-approves-two-new-treatments-heavily-pretreated-multiple-myeloma. Accessed 16 June 2024.

Kanas, Gena et al. “Estimate of Multiple Myeloma Patients by Line of Therapy in the USA: Population-level Projections 2020-2025.” Future Oncology (London, England), vol. 17.8, 2021, pp. 921-930, doi:10.2217/fon-2020-0970. Accessed 16 June 2024.

Moehler, Thomas. Multiple Myeloma. Berlin: Springer, 2013.

“Multiple Myeloma - Multiple Myeloma Information.” American Cancer Society, www.cancer.org/cancer/types/multiple-myeloma.html. Accessed 16 June 2024.

“Multiple Myeloma: More Common Than You Think.” Rutgers Cancer Institute of New Jersey, 1 Mar. 2022, www.cinj.org/multiple-myeloma-more-common-you-think. Accessed 16 June 2024.

Padala, Sandeep A., et al. "Epidemiology, Staging, and Management of Multiple Myeloma." Medical Sciences, vol. 9, no. 1, 2021, doi.org/10.3390/medsci9010003. Accessed 16 June 2024.

Price, Pat, and Karol Sikora. Treatment of Cancer. 6th ed. Boca Raton: CRC, 2015.

Stallard, Jim. “Multiple Myeloma: Improved Prognosis With the Latest Treatments.” Memorial Sloan Kettering Cancer Center, 16 Aug. 2023, www.mskcc.org/news/multiple-myeloma-improved-prognosis-latest-treatments. Accessed 16 June 2024.

Other Resources

International Myeloma Foundation

Multiple Myeloma Research Foundation