Myeloma: causes, symptoms and therapies

A blood disorder with an insidious and often asymptomatic onset that affects some bone marrow cells.

In Europe there are 39,000 new cases every year, of which over 5,000 only in Italy. It generally occurs after the age of 60 and is more frequent in men than in women. We are talking about myeloma, or plasmacytoma, a rare blood cancer that affects plasma cells, one of the cell types found in the bone marrow.

Different pathologies, one target

There are many blood diseases, and not all of them are cancerous. One of the most “famous” diseases is undoubtedly leukemia, caused by the excessive proliferation of stem cells that give rise to all the cellular elements present in the blood.

Then there are lymphoma (neoplasm caused by the uncontrolled growth of a particular type of white blood cell, the lymphocyte), different types of anemia and other diseases that manifest themselves with the lack of one or more blood components.

Myeloma, as mentioned, involves plasma cells.

Myeloma and plasma cells

Plasma cells represent one of the cellular elements found in the bone marrow. They are the result of the maturation of white blood cells and in particular of B lymphocytes, one of the main types of cells involved in the immune response.

Their role is to produce antibodies, also called immunoglobulins, and their proper functioning is therefore essential to protect the body from the attack of viruses, bacteria or other pathogens.

Under normal conditions, each plasma cell produces a slightly different type of antibody from those produced by other cells: this guarantees our immune system a specific response against a wide variety of dangerous microorganisms.

Multiple myeloma represents the evolution of a condition known as monoclonal gammopathy. It is a disease characterized by the alteration of plasma cells, which begin to grow and proliferate in an uncontrolled way, generating clones of themselves and producing numerous copies of the same antibody.

What happens?

In the case of myeloma, cancer cells produce in large quantities a protein known as the M component (monoclonal component), a particular type of antibody, which does not however possess its immunological defense prerogatives; This protein can also cause increased blood viscosity and kidney damage.

In addition, abnormal proliferation of plasma cells can result in a reduction in the normal production of other blood cells such as white blood cells, red blood cells and platelets. The consequences are:

• a weakening of normal immune defenses
• coagulation problems
• anaemia.

In addition, cancer cells produce a substance that stimulates osteoclasts, which are responsible for the destruction of bone tissue. This generates an imbalance in bone metabolism, resulting in bone fragility. Myeloma patients are often subject to pathological fractures, vertebral sagging and bone pain.

What are the causes?

To date, the causes of this neoplasm are not yet clear: it is possible that there is a hereditary factor, or a genetic predisposition that characterizes members of the same family.

However, elements related to the surrounding environment can also increase the risk of this disease, such as direct exposure to:

• ionizing radiation
• chemicals such as benzene and/or pesticides.

Chronic infections can also play an important role in the genesis of this type of cancer.

Finally, clinical studies have allowed to observe that multiple myeloma represents the progression of a monoclonal gammopathy, initially without symptoms. Every year, in fact, 1 in 100 people affected by this disease experiences multiple myeloma. There is no way to avoid this evolution or to predict if and when it will happen: the only way is to undergo regular checks, to check the state of the disease and its level of progression.

What are the symptoms?

The symptoms of myeloma can vary, and in the early stages of this condition, they may not be noticeable.

The most commonly observed symptom is that related to bone pain, particularly at the level of the spine or rib. The following may also occur:

• Fractures
• nausea
• constipation
• loss of appetite
• lightheadedness and mental confusion
• exhaustion
• frequent infections
• weight loss
• weakness in the legs
• excessive thirst.

As mentioned, the proliferation of cancer cells in the bone marrow causes several consequences, including, for example:

• hypercalcemia, or the presence of large amounts of calcium in the blood, generated in turn by the destruction of bones by osteoclasts
• impairment of hematopoiesis, which is the process of production of cells present in the bloodstream.

Anemia can therefore occur, which explains why many myeloma patients experience severe fatigue.

Other symptoms may be neurological, often due to vertebral failure.

Diagnosing myeloma: what tests to do?

Since in most cases the symptoms do not appear immediately, it is difficult to detect this disease early.

Usually, in fact, the diagnosis is reached following routine tests, such as a common blood test.

To confidently detect myeloma, you need:

• blood tests, which, thanks to laboratory techniques such as electrophoresis, allow to detect the presence of high levels of immunoglobulins, produced by cancer cells. Through the use of this test it is also possible to measure the values of hemoglobin, platelets and albumin in serum, which are low if the tumor is in an advanced stage. High levels of beta-2 microglobulin and calcium also indicate that myeloma has reached an advanced stage, and therefore a worse prognosis. The blood test also allows to verify kidney function, red blood cell count, circulating calcium levels, the amount of uric acid
• urine test, which shows the presence of abnormal plasma-derived proteins
• bone marrow biopsy, a fundamental tool for the diagnosis of myeloma. The marrow is aspirated with a syringe and analyzed for any cancer cells
• instrumental examinations, such as radiography, magnetic resonance imaging, positron emission tomography (PET), computed axial tomography (CT), used to detect abnormalities at the level of the bones, caused by the disease, and definitively confirm the diagnosis.

Multiple myeloma is defined as symptomatic, or active, when it causes organ damage, such as:

• lytic lesions, that is, destruction of bone tissue
• anaemia
• Renal
• hypercalcaemia.

After performing these tests and evaluating the results, the specialist can come to a diagnosis based on the presence of three elements:

• Serum monoclonal component
• plasma cells located in the bone marrow
• damage to some organs caused by the neoplasm.

Amyloidosis: when myeloma becomes complicated

There are pathologies that can be associated with the appearance of multiple myeloma: one of them is amyloidosis. It is a disease characterized by the formation of clusters of proteins aggregated to each other, defined by the name of amyloid, which accumulate in different tissues of the body. These deposits are formed by fragments of antibodies, the light chains, also produced by plasma cells.

Over time, aggregates accumulate in different areas of the body, causing serious damage to several organs, particularly the kidneys, heart and gastrointestinal tract.** The only exception is the central nervous system where, thanks to the blood-brain barrier, amyloid aggregates cannot reach.

Treating myeloma: different weapons to fight the same disease

A definitive cure for myeloma does not yet exist. However, innovative therapies are available that allow good control of the disease and a better quality of life.

Therapy against this neoplasm includes:

• drugs whose action is to destroy cancer cells or control tumor proliferation, in case of recurrence
• pharmacological agents or medical-surgical procedures for the prevention and treatment of disorders caused by the disease, such as bone pain, fractures and anemia, with the aim of improving the quality of life of patients.

However, it is not said that all people with myeloma should undergo therapy. In the event that the symptoms have not yet appeared, in fact, it is possible that specialists in hematology opt for constant observation and monitoring, before proceeding with a real therapeutic intervention.

Transplantation as the first choice

Autologous transplantation is the first choice approach for patients with optimal age and general physical condition, and in cases where the tumor causes compression of the vertebrae, leading to paralysis or other serious disorders.

The procedure involves collecting healthy stem cells from the patient’s bone marrow, who then undergoes one or more cycles of chemotherapy or radiotherapy, which can cause some side effects.

At this point, the previously collected healthy cells will be reinfused into the patient, which can reform a healthy marrow.

It is also possible to take bone marrow cells from a healthy donor, and perform the same reinfusion procedure on the sick patient. In this case we speak of allogeneic transplantation.

If after an autologous transplant the risk that the disease will recur, putting the patient’s survival at risk, is quite high, in the case of allograft the possibility of a recurrence decreases. On the other hand, with the latter technique mortality is higher, due to the rejection phenomena that can occur.