Multiple myeloma (MM) is a hematological malignancy characterised by the clonal proliferation of malignant plasma cells in the bone marrow.

Pathogenesis – the causes of multiple myeloma

The exact causes of MM remain unclear, but several factors have been implicated, including genetic abnormalities, environmental exposures and viral infections. The most common chromosomal abnormalities associated with MM include translocations involving the immunoglobulin heavy chain (IgH) locus on chromosome 14. These translocations result in the overexpression of oncogenes, such as MYC and cyclin D1, leading to the uncontrolled proliferation of plasma cells.

Clinical presentation – symptoms of the disease

The clinical presentation of MM is diverse, ranging from asymptomatic disease to a rapidly progressing illness. Common symptoms include:

• bone pain due to bone lesions caused by myeloma cells
• fatigue due to anemia, often a consequence of bone marrow infiltration by myeloma cells
• recurrent infections, with impaired immune function due to bone marrow suppression and abnormal antibody production
• renal dysfunction caused by monoclonal immunoglobulin light chains is deposited in the kidneys
• elevated calcium levels in the blood, leading to confusion, lethargy and the development of kidney stones.

Diagnosis – testing for multiple myeloma

The diagnosis of MM typically involves a combination of laboratory tests and imaging studies. Key diagnostic tests include:

• blood tests to conduct a complete blood count and assess kidney function and levels of monoclonal protein in the blood
• urine tests to detect the presence of Bence-Jones proteins, which are monoclonal light chains excreted in the urine
• bone marrow biopsies to confirm the presence of malignant plasma cells in the bone marrow
• iImagingstudies (such as X-rays, CT scans and MRIs) to evaluate bone lesions and assess organ involvement.  Assessing organ involvement is important for determining the stage of the disease and planning treatment.

Treatment – a combination of modalities

The treatment of MM has significantly improved in recent years, with a focus on achieving deep and durable responses. Treatment strategies typically involve a combination of the following modalities:

• Chemotherapy: Drugs such as bortezomib, lenalidomide, and pomalidomide are commonly used to target and kill myeloma cells.
• Immunotherapy: Drugs such as daratumumab and elotuzumab harness the immune system to attack myeloma cells.
• Corticosteroids: Corticosteroids such as dexamethasone can help reduce inflammation and kill myeloma cells.
• Stem cell transplantation: Autologous stem cell transplantation involves harvesting and storing healthy stem cells from the patient’s bone marrow, followed by high-dose chemotherapy to eliminate the cancer cells. The stem cells are then reinfused to restore bone marrow function.
• Novel agents: New drugs targeting specific molecular pathways involved in myeloma pathogenesis are continually being developed and tested in clinical trials.

Prognosis and future directions

The prognosis for individuals with MM has improved significantly in recent years, with many patients achieving long-term remission. However, the disease remains incurable and relapse is common. Ongoing research is focused on developing more effective therapies, including targeted therapies, CAR-T cell therapy, and bispecific antibodies.

Additionally, there is a growing emphasis on early detection and prevention of MM. Identifying individuals at high risk for developing MM through genetic testing and lifestyle modifications may help reduce the incidence of this disease. Currently, there is no definitive evidence that genetic testing and lifestyle modifications can directly reduce the risk of MM. However, research is ongoing, and some promising areas are being explored.