Multiple Myeloma: Causes, Symptoms and Treatment

What is Multiple Myeloma?

Multiple myeloma (also called plasmacytoma or myeloma) is a malignant cancer of the bone marrow. It develops when plasma cells – a type of white blood cell responsible for producing antibodies – become abnormal and multiply uncontrollably. Instead of producing functional antibodies, these malignant plasma cells produce a useless protein known as M-protein or paraprotein, which accumulates in the blood and urine.

Multiple myeloma is classified as a hematological malignancy (blood cancer) and is the second most common blood cancer after non-Hodgkin lymphoma. It primarily affects older adults, with a median age at diagnosis of approximately 70 years.

Causes and Risk Factors

The exact causes of multiple myeloma are not yet fully understood. Several factors are known to increase the risk of developing the disease:

• Genetic mutations: Chromosomal changes and mutations in plasma cells play a key role in the development of myeloma.
• Precursor condition MGUS: Multiple myeloma often develops from a benign precursor condition called monoclonal gammopathy of undetermined significance (MGUS).
• Age: The risk increases significantly with age.
• Sex: Men are slightly more likely to develop the disease than women.
• Ethnicity: People of African descent have a higher risk of developing multiple myeloma.
• Radiation and chemical exposure: Exposure to ionizing radiation or certain chemicals may increase the risk.
• Family history: First-degree relatives of individuals with myeloma have a slightly elevated risk.

Symptoms

Multiple myeloma may be asymptomatic for a long period and is often discovered incidentally during routine blood tests. Classic symptoms are commonly summarized using the acronym CRAB:

• C – Calcium elevated (hypercalcemia): Nausea, confusion, constipation, and excessive thirst.
• R – Renal insufficiency (kidney damage): Impaired kidney function caused by the deposition of M-proteins.
• A – Anemia: Fatigue, weakness, and pallor due to displacement of normal blood cells in the bone marrow.
• B – Bone lesions: Bone pain (often in the back or ribs), pathological fractures, and osteoporosis caused by the destruction of bone tissue.

Additional symptoms may include recurrent infections due to a weakened immune system, tingling or numbness in the limbs (peripheral neuropathy), and general fatigue.

Diagnosis

The diagnosis of multiple myeloma is established through a combination of tests:

Laboratory Tests

• Complete blood count: Detection of anemia or other blood count abnormalities.
• Serum protein electrophoresis and immunofixation: Detection of the M-protein in the blood.
• Serum free light chain assay: A sensitive method for detection and monitoring of the disease.
• Urine analysis: Detection of Bence Jones proteins (light chains excreted in urine).
• Kidney function and calcium levels: Assessment of organ damage.

Bone Marrow Biopsy

A bone marrow biopsy is the gold standard for diagnosis. It allows direct identification of myeloma cells and determination of their proportion among all cells in the bone marrow.

Imaging

• Whole-body MRI or PET-CT: Assessment of bone lesions and tumor spread throughout the body.
• X-ray: Detection of osteolytic lesions (areas of bone destruction).

Treatment

Multiple myeloma is currently not curable in most cases, but it is highly treatable. The goals of therapy are to control the disease, relieve symptoms, and maintain quality of life. Treatment is tailored to the individual based on age, overall health, and disease characteristics.

Systemic Therapy

• Proteasome inhibitors (e.g., bortezomib, carfilzomib): Block protein degradation pathways within cancer cells, leading to cell death.
• Immunomodulatory drugs (IMiDs) (e.g., thalidomide, lenalidomide, pomalidomide): Stimulate the immune system and inhibit tumor growth.
• Monoclonal antibodies (e.g., daratumumab, elotuzumab): Target specific surface markers on myeloma cells.
• Corticosteroids (e.g., dexamethasone): Used in combination with other agents to enhance treatment efficacy.
• CAR-T cell therapy and bispecific antibodies: Novel immunotherapies for patients with relapsed or refractory disease.

High-Dose Chemotherapy and Autologous Stem Cell Transplantation

For eligible patients (typically under 70 years of age and in good general health), induction therapy is followed by high-dose chemotherapy and autologous stem cell transplantation. The patient's own stem cells are collected before high-dose treatment and reinfused afterwards to restore normal bone marrow function.

Supportive Care

• Bisphosphonates (e.g., zoledronic acid): Protect bone tissue and reduce the risk of fractures.
• Erythropoiesis-stimulating agents and blood transfusions: Management of anemia.
• Antibiotic prophylaxis: Reduction of infection risk.
• Pain management: Individualized treatment of bone pain.

Prognosis

The prognosis of multiple myeloma has improved significantly in recent years thanks to advances in treatment. The 5-year survival rate now ranges from 50 to over 70 percent depending on the disease stage and risk group. Many patients achieve prolonged remission periods during which the disease causes no active symptoms. However, multiple myeloma typically follows a relapsing-remitting course, with periods of remission followed by relapse.

References

1. Rajkumar SV. Multiple myeloma: 2022 update on diagnosis, risk stratification, and management. American Journal of Hematology. 2022;97(8):1086-1107.
2. Kumar SK, Rajkumar V, Kyle RA, et al. Multiple myeloma. Nature Reviews Disease Primers. 2017;3:17046.
3. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Multiple Myeloma. Version 2024. Available at: www.nccn.org