Multiple myeloma
What is it?
Multiple myeloma is a cancer of plasma cells. Normal plasma cells are a type of white blood cell that belongs to the immune system and are responsible for producing antibodies when there is an infection. They are located within the bone marrow, the spongy interior of bones that produces blood cells. If a plasma cell begins to multiply uncontrollably, it becomes cancerous, invades the bone marrow, and hinders the production of healthy blood cells. Moreover, instead of producing infection-fighting antibodies, it produces an abnormal, nonfunctional antibody called a monoclonal protein (or monoclonal component).
Myeloma types vary according to the monoclonal protein produced and biological behavior. The most frequently produced antibody is IgG or IgA, less frequent are IgM, IgD and IgE. These antibody "fractions" associate with a subcomponent, called "light chains," kappa or lambda, which may also constitute the only monoclonal protein produced by the myeloma. In this case, we speak of micromolecular myeloma.
Other types of multiple myeloma produce little or no protein, and in this case we speak of oligo-secreting or non-secreting myeloma.
The exact type of monoclonal component produced, however, does not affect the course of diagnosis and treatment. In addition, there are conditions in which the tumor is localized to a single bone or extra-osseous site, which is the case with solitary plasmacytoma, or invades the entire bone marrow and appears in the peripheral blood. In the latter case, we speak of plasma cell leukemia.
Causes and risk factors
The exact cause of multiple myeloma is unknown, and risk factors to avoid have not been identified. However, they may increase the likelihood of developing the disease:
- advanced age;
- gender: men are slightly more likely to develop myeloma;
- ethnicity: African-American individuals are at higher risk of developing myeloma;
- radiation exposure;
- family history: if a parent, brother, or sister has the disease, the risk of developing myeloma increases;
- obesity;
- other plasma cell disease: the precancerous condition called monoclonal gammopathy of undetermined significance (MGUS) may predispose to the development of multiple myeloma.
Which are the symptoms?
Multiple myeloma often has no early symptoms. This can make diagnosis difficult. When present, symptoms may include:
- fatigue and/or breathlessness caused by anemia, that is, deficiency of red blood cells;
- bone pain, especially in the middle and/or lower back, rib cage, or hips, or bone fractures, due to the fact that myeloma cells result in the destruction of the surrounding bone;
- mental confusion due to possible elevated blood calcium levels and/or renal failure;
- leg swelling brought about by damage caused by multiple myeloma to the kidneys;
- nausea and decreased appetite due to elevated blood calcium levels and/or renal failure;
- excessive thirst due to high blood calcium levels and kidney damage;
- frequent infections, as myeloma cells replacing normal white blood cells decrease normal immune defenses. Common myeloma infections include pneumonia, urinary tract or kidney infections, sinusitis, and skin infections.
How is it diagnosed?
In case of symptoms suggestive of multiple myeloma or occasional finding of alteration on protein tests, a medical examination and interview will be conducted. In-depth blood and instrumental tests will then be prescribed:
- blood tests: to detect the presence of a monoclonal component in the blood, serum protein electrophoresis, immunofixation, and serum free light chain assay must be performed. In addition, blood calcium levels, hemoglobin, and renal function are assessed with blood tests;
- urine tests: protein electrophoresis in urine (on single urination or 24-hour collection) can detect the presence of Bence Jones protein, the abnormal protein produced by plasma cells;
- myeloaspirate and bone marrow biopsy: using a long needle attached to a syringe, the doctor aspirates a small amount of bone marrow and a fragment of bone to examine under a microscope to determine and quantify cancer cells. This examination also provides genetic information about the aggressiveness of myeloma;
- tumor biopsy: multiple myeloma in localized form or with extra bony masses (plasmacytomas) can be biopsied or surgically removed and examined under a microscope;
- instrumental examinations, such as CT (Computed Axial Tomography), PET (Positron Emission Tomography), and magnetic resonance imaging (MRI), are necessary to define the extent of disease at the bone or extraosseous level.
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How is it treated?
Once the diagnosis is confirmed, myeloma treatment is discussed and proposed by specialists based on a comprehensive evaluation that takes into account several factors, including the type and biology of the tumor, age, and the patient's general health condition. One or more of the following strategies may be recommended:
- watch and wait: for patients with asymptomatic (smoldering) myeloma, an approach of careful observation with regular checkups without active treatment may be appropriate;
- targeted therapy, chemotherapy, and immunotherapy: targeted therapy includes drugs that specifically target the biology of cancer cells to stop their growth and spread and includes drugs such as proteasome inhibitors and immunomodulators administered in different combinations or individually. More traditional chemotherapy and corticosteroids are often used in combination with these therapies.
Immunotherapy consists of a set of drugs and strategies that enhance the immune response to fight cancer cells and involves:
- monoclonal antibodies that selectively bind on plasma cells and promote immunological activity against them (among them: daratumumab, isatuximab and elotuzumab);
- bispecific antibodies, or molecules that help activate and bring immune system cells alongside myeloma cells to destroy them;
- T cell chimeric antigen receptor (CAR-Ts), or T cells, genetically modified to selectively attack myeloma;
- radiation therapy: plays a valuable role in providing rapid pain relief and reducing the risk of bone fractures. It can be particularly useful in the case of tumors present in only one location (solitary plasmacytoma);
- stem cell transplantation: depending on the health status and age of the patient, autologous stem cell transplantation (or bone marrow transplantation) may be proposed. After reduction of myeloma cells with initial therapies, healthy stem cells will be taken from the patient. They will be reinfused after administration of high-dose chemotherapy, which the patient will receive during hospitalization.
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