Multiple Myeloma

What is Multiple Myeloma?

Multiple Myeloma is a type of cancer that forms in plasma cells, a kind of white blood cell that helps the body fight infections by making antibodies. In multiple myeloma, cancerous plasma cells accumulate in the bone marrow and crowd out healthy blood cells.

Causes and Risk Factors

The exact cause of multiple myeloma is not fully understood, but several risk factors have been identified:

Age: Most people diagnosed with multiple myeloma are over 65.
Gender: Men are slightly more likely to develop the disease than women.
Race: African Americans have a higher risk compared to other races.
Family history: A family history of multiple myeloma or other blood cancers may increase risk.
Monoclonal gammopathy of undetermined significance (MGUS): This condition can develop into multiple myeloma over time.

Symptoms of Multiple Myeloma

Common symptoms include:

Bone pain, especially in the spine or chest
Frequent infections due to a weakened immune system
Fatigue or feeling weak
Weight loss without trying
Excessive thirst and dehydration
Nausea or constipation
Kidney problems caused by high levels of abnormal proteins

Diagnosis and Staging

Diagnostic Tests

To diagnose multiple myeloma, doctors may use the following tests:

Blood tests: To detect abnormal proteins (M proteins), calcium levels, and other indicators.
Urine tests: To check for the presence of Bence Jones proteins, which indicate multiple myeloma.
Bone marrow biopsy: A sample of bone marrow is taken to look for myeloma cells.
Imaging tests: Such as X-rays, MRI, CT scans, or PET scans to detect bone damage.

Staging

Staging of multiple myeloma helps determine the extent of the disease:

Stage I: Early stage with fewer cancerous cells.
Stage II: Intermediate stage, with a moderate amount of myeloma cells.
Stage III: Advanced stage with many cancerous cells and potential organ damage.

Treatment Options

Treatment varies based on the stage and the patient’s overall health:

Targeted therapy: Drugs that target specific proteins in myeloma cells, such as proteasome inhibitors.
Immunotherapy: Utilizes the immune system to fight cancer, using drugs that enhance the immune response.
Chemotherapy: Kills rapidly growing cancer cells and is often used before stem cell transplant.
Stem cell transplant: Involves replacing damaged bone marrow with healthy stem cells, typically following high-dose chemotherapy.
Radiation therapy: Used to relieve pain and reduce the size of tumors in specific areas.

Prognosis

The prognosis for multiple myeloma depends on various factors, including the stage at diagnosis and the patient's response to treatment. While it is generally considered incurable, advancements in treatment have significantly improved survival rates and quality of life for patients.

Key Research Papers

Historical Background

Multiple myeloma was first described in 1844 by Samuel Solly, who reported a case of bone disease associated with fragile bones. In 1848, Henry Bence Jones identified the characteristic urinary protein (now called Bence Jones protein). The disease was formally characterized by Otto Kahler in 1889, and for many years was known as "Kahler's disease." Jan Gosta Waldenstrom further distinguished myeloma from other plasma cell disorders in the 1940s.

Facon T, Kumar S, Plesner T, et al. Daratumumab plus lenalidomide and dexamethasone for untreated myeloma (MAIA). N Engl J Med. 2019;380(22):2104-2115. — doi:10.1056/NEJMoa1714678
Munshi NC, Anderson LD Jr, Shah N, et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma (KarMMa). N Engl J Med. 2021;384(8):705-716. — doi:10.1056/NEJMoa2024850
Rajkumar SV. Multiple myeloma: 2020 update on diagnosis, risk-stratification, and management. Am J Hematol. 2020;95(5):548-567. — doi:10.1002/ajh.25791
Lonial S, Dimopoulos M, Palumbo A, et al. Elotuzumab therapy for relapsed or refractory multiple myeloma (ELOQUENT-2). N Engl J Med. 2015;373(7):621-631. — doi:10.1056/NEJMoa1505654
Dimopoulos MA, Oriol A, Nahi H, et al. Daratumumab, lenalidomide, and dexamethasone for multiple myeloma (POLLUX). N Engl J Med. 2016;375(14):1319-1331. — doi:10.1056/NEJMoa1607751
Palumbo A, Chanan-Khan A, Weisel K, et al. Daratumumab, bortezomib, and dexamethasone for multiple myeloma (CASTOR). N Engl J Med. 2016;375(8):754-766. — doi:10.1056/NEJMoa1606038
Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15(12):e538-e548. — doi:10.1016/S1470-2045(14)70442-5
Stewart AK, Rajkumar SV, Dimopoulos MA, et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma (ASPIRE). N Engl J Med. 2015;372(2):142-152. — doi:10.1056/NEJMoa1411321
Cowan AJ, Green DJ, Kwok M, et al. Diagnosis and management of multiple myeloma: a review. JAMA. 2022;327(5):464-477. — doi:10.1001/jama.2022.0003
Greipp PR, San Miguel J, Durie BGM, et al. International staging system for multiple myeloma (ISS). J Clin Oncol. 2005;23(15):3412-3420. — doi:10.1200/JCO.2005.04.242
Moreau P, Garfall AL, van de Donk NWCJ, et al. Teclistamab in relapsed or refractory multiple myeloma (MajesTEC-1). N Engl J Med. 2022;387(6):495-505. — doi:10.1056/NEJMoa2203478
Richardson PG, Oriol A, Beksac M, et al. Pomalidomide, bortezomib, and dexamethasone for patients with relapsed or refractory multiple myeloma (OPTIMISMM). Lancet Oncol. 2019;20(6):781-794. — doi:10.1016/S1470-2045(19)30152-4

PubMed Topic Searches

The following PubMed topic searches surface the current peer-reviewed literature on Multiple Myeloma. Each link opens a live PubMed query; results update as new papers are indexed.

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