Multiple myeloma

Content

Introduction

Multiple myeloma or simply myeloma, it is a cancer that develops from certain blood cells found in the bone marrow. The bone marrow is the spongy tissue, present in the central part of some bones, which has the task of producing blood cells.

In myeloma, plasma cells, cells specialized in the production of antibodies, are altered gammaglobulins. Excessive reproduction of plasma cells causes the bone marrow to expand to the point of causing swelling and, sometimes, fracture of the bones and an increase in antibodies in the blood.

Myeloma often occurs in many areas of the body and is therefore called multiple. The most commonly affected areas are:

  • vertebral column
  • skull
  • hip bone
  • ribs

It may happen that in the early stages myeloma does not cause any symptoms. In these cases, the diagnosis is made on the occasion of a blood or urine analysis, carried out for other reasons from which an abnormal increase in the quantity of gamma globulins emerges.

When present, symptoms include:

  • fixed pain or a feeling of soft bones in particular areas of the body
  • bone fragility, with ease to fracture of the bone
  • tiredness, weakness and shortness of breath caused by anemia
  • repeated infections
  • bruising and bleeding, such as nosebleeds, gum bleeds or heavy periods.

The symptoms described above are also common to other diseases but should they occur, it is still advisable to contact your doctor.If you suspect that you have myeloma, your doctor may order specific blood and urine tests that can identify the abnormal proteins produced by myeloma cells. If the results of the tests were to be altered, the doctor will request a visit to the haematologist, the specialist in blood diseases, for further tests and for the most suitable treatments.

Multiple myeloma is an uncommon type of cancer. Every year in Italy the number of new cases is 6.6 per 100,000 people in men and 4.5 per 100,000 people in women.

The cause of the disease is not yet known, although it most commonly occurs in:

  • people with too many gammaglobulins in their blood (monoclonal gammopathy of uncertain significance, MGUS)
  • men
  • adults over 60, the majority of cases are diagnosed around 70 years of age, while cases under 40 are rare
  • coloured people, the frequency of myeloma is approximately twice as high in black people as in white people and in the Asian population

For myeloma there are different chemotherapy schemes that use different combinations of drugs (melphalan, prednisone, cyclophosphamide, vincristine, doxorubicin), to these are added new drugs such as: thalidomide, lenalidomide, bortezomib, pomalidomide. Sometimes localized radiotherapy can be used and more rarely surgery.

Bisphosphonates can be used to treat bone damage.

In more advanced cases it is possible to resort to stem cell transplantation.

The outlook for life for multiple myeloma is steadily improving over time, and research in this area is showing progress.

Symptoms

In the early stages of development, multiple myeloma does not always cause symptoms or complications and, for this reason, in some cases it is diagnosed during tests performed for other reasons.

When symptoms are present, however, they include:

  • bone pain, most often affects the back, ribs and hips. Often, it is somber, deep and persistent and gets worse with movement
  • bone fractures and spinal cord compression, multiple myeloma can weaken bones and make them more prone to fractures. Spine and ribs are at increased risk of fractures. When the fracture affects the spine, some of its sections may collapse with the appearance of pain and, sometimes, compression of the spinal cord, the bundle of nerves that runs down the back
  • anemiamultiple myeloma can affect the bone marrow's production of blood cells, causing anemia, which is a decrease in red blood cells. Anemia can also occur as a side effect of anti-myeloma medications. The anemic person may feel very tired and weak and experience shortness of breath
  • recurrent infections, people with myeloma can frequently get infections because the disease interferes with the body's defense system (immune system)
  • increased level of calcium in the blood (hypercalcemia), caused by the elevated release of calcium from the bones affected by lymphoma. Symptoms caused by hypercalcemia include: insatiable thirst, malaise, need to urinate frequently, constipation, confusion and sleepiness
  • unusual bleedingoccasionally there may be bleeding from the gums, nose, heavy menstrual periods and bruising on the skin. The explanation for this symptom lies in the blocking of the production of platelets (blood cells that have the task of preventing blood loss) induced by myeloma cells
  • increased blood density, in some people the blood may become thicker than normal (called hyperviscosity of the blood) and, as a result, blurred vision, headache, dizziness, bleeding from the gums or nose, and shortness of breath may appear
  • kidney disorders, kidney damage can occur in people with myeloma due to the production of abnormal proteins by cancer cells, hypercalcemia, or drugs used to treat myeloma. With kidney damage, the kidneys can function poorly or even become completely blocked. Symptoms in this case include:
    • loss of weight and appetite
    • swollen ankles, feet and hands
    • fatigue and lack of energy
    • shortness of breath
    • itchy skin
    • generalized malaise

Causes

Multiple myeloma arises from the tumor transformation of a type of bone marrow cell, called plasma cells. Usually, plasma cells are produced in a controlled manner but in the case of myeloma they reproduce in excessive numbers and fill the bone marrow, interfering with the production of other types of blood cells such as red blood cells and white blood cells.

Why this happens is unknown but it is known to be associated with a called condition monoclonal gammopathy of uncertain significance (MGUS) and that some factors increase the risk of developing myeloma.

Monoclonal Gammopathy of Uncertain Significance (MGUS)

In nearly all cases, multiple myeloma occurs in people with MGUS.

MGUS consists of the presence of high levels in the blood of abnormal proteins called immunoglobulins.

MGUS causes no symptoms and requires no treatment. However, about 1 in 100 people with MGUS develop multiple myeloma each year. There is no known way to prevent or delay it but people with MGUS are recommended to undergo periodic outpatient check-ups at a specialized hematology center.

Other factors

Other factors that can increase the risk of developing multiple myeloma include:

  • age, the risk increases over time; the majority of cases, in fact, are diagnosed at the age of about 70, while under 40, cases are rare
  • gender, men are more likely than women to develop myeloma
  • ethnicity, myeloma is twice as common in ethnic African Americans as in Caucasians

The still uncertain role of other factors has been suggested, such as:

  • family members with MGUS
  • family members with multiple myeloma
  • impaired functioning of the immune system (for example, due to medication or HIV infection)
  • overweight or obesity
  • radiation or some chemicals

Diagnosis

Diagnosis of multiple myeloma is difficult due to its rarity and the initial absence of symptoms.

Doctors may suspect myeloma based on the symptoms present and the person's general health. When this happens, he usually prescribes a visit to the haematologist to complete the investigations with further tests and x-rays.

Blood analysis

Blood tests allow you to look at the levels of certain substances and processes which include:

  • erythrocyte sedimentation rate (ESR), or blood viscosity (PV). In the case of multiple myeloma these values ​​are usually higher
  • measurement of the type and quantity of abnormal antibodies, produced by tumor plasma cells
  • hematocrit with formula, count of different types of blood cells. The hematologist checks if there is a reduced number of red blood cells and platelets
  • indicators of liver and kidney function
  • blood calcium level

Urine analysis

It is used to evaluate the presence of abnormal proteins, produced by tumor plasma cells, known by the name of monoclonal light chains or Bence Jones proteins. These proteins, when passing from the blood to the urine, can damage the kidneys. A 24-hour urinalysis will measure the amount of protein produced and check the functioning of the kidneys.

X-rays and other types of investigations

  • x-ray radiography, useful for looking for damage to long bones (arms and legs), skull, spine and pelvis
  • computed tomography (CT)
  • magnetic resonance imaging (MRI)
  • bone marrow biopsy, test necessary to diagnose the presence of multiple myeloma. It consists in taking a small sample of bone marrow using a needle, usually from the bones of the pelvis, to look for the presence of tumor plasma cells

Therapy

The group of doctors led by the hematologist indicates, among the various possibilities available, the one they consider to be the best cure and shares the choice with the person with myeloma, who has the final decision. It is therefore advisable to prepare a list of questions to be addressed to doctors in writing and to be well informed about the advantages and disadvantages of each treatment before going to the hospital to receive treatment.

The treatment of myeloma has two main objectives:

  • keep the disease under control
  • prevent and treat ailments caused by myeloma, such as anemia and bone pain

The therapy is able to control the tumor and improve the quality of life of the person with myeloma but it is not able to cure it definitively. This implies that further treatment will be needed when the cancer recurs.

However, if myeloma does not cause symptoms, immediate treatment is not required but periodic checks should be performed to immediately recognize any signs of its progression.

If, on the other hand, myeloma needs to be treated, the most commonly used therapies include:

  • non-intensive initial treatment, for older people or people who are not in good health (it is the most common)
  • intensive initial treatment, for younger or healthy people (considered too toxic for elderly or unhealthy people). This therapy involves the use of drugs in high doses followed by bone marrow stem cell transplantation. Combined drugs consist of a chemotherapy drug, a steroid drug and either thalidomide or bortezomib
    Both treatments consist of having to take a combination of anti-myeloma drugs
  • chemotherapy, chemotherapy drugs are able to eliminate myeloma cells. The types most commonly used to treat myeloma are melphalan and cyclophosphamide. Mostly the drugs are in tablet form, are reasonably well tolerated, and side effects are mild. Possible side effects are:
    • increased risk of getting infections
    • malaise
    • He retched
    • hair loss
  • steroids, steroid drugs (cortisone) help eliminate myeloma cells and increase the effectiveness of chemotherapy. The two most common types to treat myeloma are dexamethasone and prednisolone. Steroids are taken by mouth (orally) after eating. Possible side effects can be heartburn, feeling full stomach, increased appetite, mood swings and trouble falling asleep.
  • thalidomide, a medicine that can help eliminate myeloma cells. The treatment consists of taking one tablet a day, usually in the evening as it induces sleepiness. Side effects can be:
    • constipation
    • dizziness
    • skin rashes
    • numbness or tingling in the hands and feet (peripheral neuropathy)
    Thalidomide cannot be taken during pregnancy because it can cause fetal defects. Therefore, women of childbearing age during treatment must use a reliable method of contraception.In addition, since there is a risk of developing blood clots during the use of thalidomide, in addition to anti-myeloma therapy it is necessary to take a drug to prevent their formation. If symptoms appear, such as pain or swelling in either leg o chest pain and difficulty in breathing (apnea), the haematologist should be contacted immediately
  • bortezomib, it can help kill myeloma cells by causing protein to build up in them. The drug is given by injection, usually under the skin. Possible side effects are:
    • tiredness
    • nausea
    • diarrhea
    • numbness or tingling in the hands and feet (peripheral neuropathy)
  • stem cell transplant, after an initial outpatient treatment the person who has received intensive care can be treated in the hospital with an even higher dose of chemotherapy in order to eliminate the largest possible number of myeloma cells. However, the high doses of the drug used also damage healthy bone marrow, so much so that a stem cell transplant is necessary to restore its function. In most cases, stem cells are taken directly from the person with myeloma before treatment (called an autologous transplant). In rare cases, they are taken from a brother or sister or even from an unrelated donor (called allogeneic transplant).

Treatment of the recurrence of the tumor

After the treatment, the person is subjected to periodic checks (blood tests and / or instrumental tests) in order to immediately identify the first signs of relapse, ie the reappearance of the disease.

Relapse therapy is usually similar to that already done, although non-intensive treatment is preferable to intensive treatment. In addition to the drugs already used, new ones such as lenalidomide, pomalidomide or other chemotherapy drugs may be used.

There is also the possibility that the "hematologist will ask the person with myeloma if they are willing to participate in a clinical trial for the testing of new drugs.

Lenalidomide and pomalidomide

Lenalidomide and pomalidomide are similar to thalidomide. Both must be taken orally and can have side effects, such as:

  • increased risk of getting infections, as a result of a low white blood cell count
  • anemia, caused by a low number of red blood cells
  • bruising and bleeding, due to a low platelet count

These drugs can also increase the risk of developing blood clots or other typical side effects of thalidomide.

Always inform the treating haematologist if any unusual problems or symptoms appear while taking lenalidomide or pomalidomide.

Treatment of myeloma symptoms and complications

Treatments to reduce the ailments or complications caused by myeloma include:

  • pain relievers, to reduce bone pain
  • radiotherapy, to relieve bone pain or reduce the number of cancer cells within the bone
  • bisphosphonates, to help prevent bone damage and reduce the level of calcium in the blood
  • blood transfusion or erythropoietin treatment, to increase the number of red blood cells and treat anemia
  • surgery, to repair or strengthen damaged bones, or to treat compression of the spinal cord, which is the bundle of nerves that runs down the back
  • dialysis, in case of kidney damage
  • plasmapheresis, to remove excess immunoglobulins from the blood and reduce viscosity

Each of these therapies could cause side effects and complications. Therefore, it is necessary to discuss this first with the haematologist to know the potential risks and benefits.

Clinical trials and research

Research is working to find new treatments for multiple myeloma and new ways to improve therapies already in use. To aid research, the hematologist may propose to participate in a clinical trial. Usually, the clinical trial is aimed at comparing a new drug with an existing one to see if the new one is more or less effective. It is important, however, to remember that a therapy based on an investigational drug does not guarantee its effectiveness and that participation must only be on a voluntary basis.

Bibliography

NHS. Multiple myeloma (English)

In-depth link

Aiom Foundation (Italian Association of Medical Oncology). Multiple myeloma. Information for patients

International Myeloma Foundation

Italian Association of Cancer Patients, Relatives and Friends (AIMaC). Multiple myeloma and other plasma cell cancers

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