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Multiple Myeloma

Multiple myeloma is a type of cancer characterized by the abnormal proliferation of white blood cells or plasma B cells and is typically accompanied by the secretion of monoclonal immunoglobulins (antibodies) that are detectable in the serum or urine.  The plasma cells which are found in the bone marrow are an important part of the immune system. Multiple myeloma accounts for around 1.6% of all cancers and 10% of all hematological cancers. According to the data of the International Agency for Research on Cancer (IARC), 176,404 new cases and 117,077 deaths have been recorded globally with multiple myeloma in the year, 2020 alone.

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Symptoms

The most common symptoms of multiple myeloma are anemia, infections, lytic or osteopenic bone disease, or kidney problems (renal failure). However, multiple myeloma can also be accidentally detected in its asymptomatic stage. Back pain, particularly in older patients, or unclear anemia is usually the first symptom that prompts screening for the presence of multiple myeloma. Frequent infections occur in patients with multiple myeloma due to a weakened immune system (a person with myeloma is immunocompromised). In myeloma patients, a shortage of red blood cells, white blood cells, and platelets is often observed which might lead to other symptoms such as anemia (reduced number of red blood cells that can cause weakness, a reduced ability to exercise, shortness of breath, and dizziness), leukopenia (reduction in the number of white blood cells that can lower resistance to infections such as pneumonia), and thrombocytopenia (lower than normal blood platelet counts which cause severe bleeding even with minor cuts, or bruises). High levels of calcium are also often observed in the blood of multiple myeloma patients, which have deleterious effects. The effects include dehydration or loss of body salts and fluids and kidney malfunctioning with renal failure. The effects may also involve constipation of severe types along with loss of appetite.

Diagnosis

Clinical evaluations, detailed patient history, and specialized tests are used to diagnose multiple myeloma which includes:

  • Removal and microscopic examination of small samples of bone marrow (biopsy or aspiration).

  • Blood tests to detect low levels of red and white blood cells.

  • Magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET) scanning may reveal characteristic changes.

  • Electrophoresis is performed to detect proteins in the blood or urine. It may be used to detect elevated levels of M-proteins. An immunoglobulin-free light chain assay of blood is considered a standard of evaluation.

Treatment

The treatment of multiple myeloma depends on whether the patient is asymptomatic or experiencing symptoms, as well as the patient’s overall health. Immediate treatment may not be necessary for multiple myeloma that is slow-growing and at an early asymptomatic stage. Individuals with pre-cancerous stages of the disease (MGUS or SMM) or early-stage myeloma and no symptoms are usually closely monitored by frequent evaluation. In case of bone thinning or osteoporosis, periodic infusions of bisphosphonates may be necessary to reverse this condition. Certain clinical protocols may be used to evaluate whether targeted therapy or immunotherapy can prevent or delay myeloma from turning malignant. Active treatment needs to be initiated once the symptoms appear.

 

The types of therapies used for multiple myeloma include chemotherapy, radiation therapy, targeted therapy, immunotherapy, steroids, bone-modifying drugs, and bone marrow or stem cell transplantation.

 

Chemotherapy

A combination of two or more chemotherapeutic drugs has been successfully used for the treatment of multiple myeloma. These drugs include cyclophosphamide, doxorubicin, melphalan, etoposide, cisplatin, carmustine, and bendamustine. Chemotherapeutic drugs may be also used in combination with other treatment options, including targeted therapies or steroids.

 

Monoclonal antibodies

Monoclonal antibodies bind to the antigens on the surface of myeloma cells, called CD 38, and label them for removal by the person's immune system. Monoclonal antibodies like daratumumab or elotuzumab, are used in those cases to treat myeloma in which patients do not respond to initial treatment, who do not qualify for stem cell therapy or those patients who have symptoms that recur after a period of remission from the disease.

Immunomodulatory drugs

Thalidomide, lenalidomide, and pomalidomide are immunomodulatory drugs, which stimulate the immune system and have anti-cancer properties. These drugs also inhibit the new blood vessels from forming and feeding the myeloma cells.

Steroids

Steroids, such as prednisone and dexamethasone, may be applied alone or in combination with other drug therapies. These are very effective at reducing the burden of the plasma cells, but this effect is only temporary.

Bone-modifying drugs

Most patients with myeloma receive treatment with bone-modifying drugs as this helps to strengthen the bone and reduce pain and the risk of fractures. There are 2 types of bone-modifying drugs available for treating multiple myeloma- bisphosphonates (such as zoledronic acid and pamidronate) and denosumab.

Radiation therapy

Radiation therapy may be recommended for patients with bone pain when chemotherapy is not effective or to control pain. However, radiation therapy may not be helpful when the pain (especially back pain) is due to structural damage to the bone, and may also affect the bone marrow's response to other treatment modalities.

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