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multiple-myeloma

What Is Multiple Myeloma?

Myeloma is cancer of the plasma cells. Plasma cells are white blood cells that produce disease- and infection-fighting antibodies in your body. Myeloma cells prevent the normal production of antibodies, leaving your body's immune system weakened and susceptible to infection. The multiplication of myeloma cells also interferes with the normal production and function of red and white blood cells. An abnormally high amount of these dysfunctional antibodies in the bloodstream can cause kidney damage. Additionally, the myeloma cells commonly produce substances that cause bone destruction, leading to bone pain and/or fractures.

Myeloma cells are produced in the bone marrow, the soft tissue inside your bones. Sometimes myeloma cells will travel through your bloodstream and collect in other bones in your body. Because myeloma frequently occurs at many sites in the bone marrow, it is often referred to as multiple myeloma.

What are plasma cells?

Plasma cells are a type of white blood cell made in the bone marrow. Bone marrow is the ‘spongy’ material found in the centre of the larger bones in the body and is where all blood cells are made.

Plasma cells form part of your immune system. Normal plasma cells produce antibodies, also called immunoglobulins, to help fight infection.

How does myeloma develop?

Myeloma develops when DNA is damaged during the development of a plasma cell. This abnormal cell then starts to multiply and spread within the bone marrow. The abnormal plasma cells release a large amount of a single type of antibody – known as paraprotein – which has no useful function.

Unlike many cancers, myeloma does not exist as a lump or tumour. Most of the medical problems related to myeloma are caused by the build-up of abnormal plasma cells in the bone marrow and the presence of the paraprotein in the body.

Myeloma affects multiple places in the body, which is why it is referred to sometimes as ‘multiple’ myeloma. Myeloma affects where bone marrow is normally active in an adult, such as in the bones of the spine, skull, pelvis, the rib cage, long bones of the arms and legs and the areas around the shoulders and hips.

What are the stages of multiple myeloma?

If you are diagnosed with multiple myeloma, your doctor will determine the stage of the disease. Staging is a way of determining how much disease is in the body and where it has spread. This information helps the doctor plan the best treatment. Once the staging classification is determined, it stays the same even if treatment is successful or the cancer spreads.

Staging multiple myeloma is based on the results of blood and imaging tests. Results of other tests can also help determine the stage depending on the system used.

Doctors use 2 systems to stage multiple myeloma:

  1. International Staging System (ISS)
  2. Durie-Salmon staging system

The most common way to diagnose the stage of the disease is through the International Staging System (ISS), which is based on two different blood test results: the beta 2-microglobulin (β2-M) and the albumin.

There are three stages of classification under the ISS:

Stage I: β2-M less than 3.5 mg/L and albumin greater than or equal to 3.5 gm/dL.

Stage II: Either β2-M greater than 3.5 mg/L but not greater than 5.5 mg/dL and/or albumin less than 3.5 g/dL.

Stage III: β2-M greater than 5.5 mg/L.

The Durie-Salmon Staging System is an older system of diagnosis. This uses four measurements to determine which stage of the disease exists:

  1. the amount of hemoglobin in the blood
  2. the amount of calcium in the blood
  3. the production rate of M protein
  4. the number of bone lesions.

The disease’s stage is then further subdivided based on kidney function.

The three stages of the disease as determined by the Durie-Salmon Staging System are: Stages I, II and III. Each of these stages is then subdivided into either Stage A or Stage B based on whether kidney function is affected. (Stage B means there is significant kidney damage.)

Stage I: Though a person with Stage I often shows no symptoms of the disease because there are fewer cancer cells present in the body, other signs will be present, such as: amount of red blood cells within or a little below the normal range, a normal amount of calcium in the blood, low levels of M protein in the urine or blood.

Stage II: More cancer cells are present in the body than in Stage I. An individual who does not fit into either Stage I or Stage III is said to have Stage II.

Stage III: There are many cancer cells present. Other characteristics of this stage include; hypercalcemia, high levels of M protein, anemia, and significant bone damage.

Note: In any stage, if kidney function is affected, the prognosis will be worse.

What are the signs and symptoms of multiple myeloma?

Signs and symptoms of multiple myeloma aren’t always easy to detect. You may not experience any of the symptoms during the cancer’s earliest phases. As the cancer advances, symptoms vary greatly. One person’s experience can be completely different from another’s.

The most common signs and symptoms of multiple myeloma include:

Fatigue: Healthy cells allow your body to fight invading germs easily. As myeloma cells replace bone marrow, your body has to work much harder with fewer disease-fighting cells, and you tire more easily.

Bone problems: Myeloma can prevent your body from making new bone cells, causing problems like bone pain, weakened bones, and broken bones.

Kidney problems: Myeloma cells produce harmful proteins that can cause kidney damage and even failure.

Low blood counts: Myeloma cells crowd out healthy blood cells, leading to low red blood counts (anemia) and low white blood cells (leukopenia). Unhealthy blood cell levels make it harder to fight infections.

Frequent infections: Fewer antibodies in your blood make fighting infections more difficult.

Other common signs and symptoms of multiple myeloma include:

  1. Nausea
  2. Weight loss
  3. Constipation
  4. Loss of appetite
  5. Weakness or loss of feeling in your legs
  6. Swelling in your legs
  7. Increased thirst
  8. Frequent urination
  9. Dizziness
  10. Confusion
  11. Pain, especially in your back or belly

What Causes Multiple Myeloma?

It's not clear what causes myeloma.

Doctors know that myeloma begins with one abnormal plasma cell in your bone marrow — the soft, blood-producing tissue that fills in the center of most of your bones. The abnormal cell multiplies rapidly.

Because cancer cells don't mature and then die as normal cells do, they accumulate, eventually overwhelming the production of healthy cells. In the bone marrow, myeloma cells crowd out healthy white blood cells and red blood cells, leading to fatigue and an inability to fight infections.

The myeloma cells continue trying to produce antibodies, as healthy plasma cells do, but the myeloma cells produce abnormal antibodies that the body can't use. Instead, the abnormal antibodies (monoclonal proteins, or M proteins) build up in the body and cause problems such as damage to the kidneys. Cancer cells can also cause damage to the bones that increases the risk of broken bones.

What are the risk factors for multiple myeloma?

A risk factor is anything that changes a person’s chance of getting a disease such as cancer. Different cancers have different risk factors. For example, exposing skin to strong sunlight is a risk factor for skin cancer. Smoking is a risk factor for lung cancer and many other cancers. But risk factors don’t tell us everything. People who have no risk factors can still get the disease. Also, having a risk factor, or even several, does not mean that a person will get the disease.

Here are a few risk factors that could affect someone’s chance of getting multiple myeloma.

Age: The risk of developing multiple myeloma goes up as people get older. Less than 1% of cases are diagnosed in people younger than 35. Most people diagnosed with this cancer are at least 65 years old.

Race: Multiple myeloma is more than twice as common in African Americans than in white Americans. The reason is not known.

Gender: Men are more likely to develop multiple myeloma than women.

Family history: If a brother, sister or parent has multiple myeloma, you have an increased risk of the disease.

Having other plasma cell diseases: People with monoclonal gammopathy of undetermined significance (MGUS) or solitary plasmacytoma are at higher risk of developing multiple myeloma than someone who does not have these diseases.

What are complications of multiple myeloma?

Multiple myeloma can cause other complications in the body due to the spreading infection in the plasma cells. If problems from multiple myeloma occur, your oncologist will discuss your treatment options to cure or contain these complications. Some of the complications often seen in multiple myeloma include:

Frequent infections: As myeloma cells crowd out healthy plasma cells, your body becomes less able to fight infections.

Anemia: Normal blood cells will be pushed out of your bone marrow and replaced by cancer cells, which can lead to anemia and other blood problems.

Bone problems: Bone pain, weakened bones, and broken bones are all common complications of multiple myeloma.

Reduced kidney function: M proteins are harmful antibodies produced by the myeloma cancer cells. They can damage your kidneys, cause problems with kidney function, and eventually lead to kidney failure. In addition, damaged and eroding bones can increase your blood’s calcium levels. These higher calcium levels can interfere with your kidneys’ ability to filter waste.

How is multiple myeloma diagnosed?

Doctors often detect multiple myeloma before any symptoms are present. Routine physical exams, blood tests, and urine tests can uncover evidence of this cancer.

More tests will be needed if your doctor finds signs of myeloma when you don’t have symptoms. Using the following tests, your doctor can monitor the progression of the disease and determine whether you need treatment.

Tests and procedures used to diagnose multiple myeloma include:

Blood tests: Laboratory analysis of your blood may reveal the M proteins produced by myeloma cells. Another abnormal protein produced by myeloma cells – called beta-2-microglobulin – may be detected in your blood and give your doctor clues about the aggressiveness of your myeloma.

Additionally, blood tests to examine your kidney function, blood cell counts, calcium levels and uric acid levels can give your doctor clues about your diagnosis.

Urine tests: Analysis of your urine may show M proteins, which are referred to as Bence Jones proteins when they're detected in urine.

Examination of your bone marrow: Your doctor may remove a sample of bone marrow for laboratory testing. The sample is collected with a long needle inserted into a bone (bone marrow aspiration and biopsy).

In the lab, the sample is examined for myeloma cells. Specialized tests, such as fluorescence in situ hybridization (FISH) can analyze myeloma cells to understand their genetic abnormalities. Tests are also done to measure the rate at which the myeloma cells are dividing.

Imaging tests: Imaging tests may be recommended to detect bone problems associated with multiple myeloma. Tests may include an X-ray, MRI, CT or positron emission tomography (PET).

Assigning a stage and a risk category

If tests indicate you have multiple myeloma, your doctor will use the information gathered from the diagnostic tests to classify your disease as stage I, stage II or stage III. Stage I indicates a less aggressive disease, and stage III indicates an aggressive disease that may affect bone, kidneys and other organs.

Your multiple myeloma may also be assigned a risk category, which indicates the aggressiveness of your disease.

Your multiple myeloma stage and risk category help your doctor understand your prognosis and your treatment options.

How is multiple myeloma treated?

If you have multiple myeloma, your healthcare team will create a treatment plan just for you. It will be based on your health and specific information about the cancer. When deciding which treatments to offer for multiple myeloma, your healthcare team will consider:

  1. your age and health status
  2. whether or not you have symptoms and which symptoms you have
  3. if you have complications of the disease, such as kidneys not working well
  4. whether or not you are eligible to have a stem cell transplant – this depends on age, performance status and if you have other health issues
  5. risk stratification based on chromosomal changes – you will be told if you are good (low) risk, intermediate risk or high risk
  6. the type of multiple myeloma
  7. the stage of multiple myeloma
  8. if you have had other treatments and how well you responded to them

Immediate treatment may not be necessary

If you have multiple myeloma but aren't experiencing any symptoms (also known as smoldering multiple myeloma), you may not need treatment. However, your doctor will regularly monitor your condition for signs that the disease is progressing. This may involve periodic blood and urine tests.

If you develop signs and symptoms or your multiple myeloma shows signs of progression, you and your doctor may decide to begin treatment.

Treatments for myeloma

Standard treatment options include:

Bone marrow transplant: A bone marrow transplant, also known as a stem cell transplant, is a procedure to replace your diseased bone marrow with healthy bone marrow.

Before a bone marrow transplant, blood-forming stem cells are collected from your blood. You then receive high doses of chemotherapy to destroy your diseased bone marrow. Then your stem cells are infused into your body, where they travel to your bones and begin rebuilding your bone marrow.

Radiation therapy: This treatment uses beams of energy, such as X-rays and protons, to damage myeloma cells and stop their growth. Radiation therapy may be used to quickly shrink myeloma cells in a specific area – for instance, when a collection of abnormal plasma cells form a tumor (plasmacytoma) that's causing pain or destroying a bone.

Chemotherapy: Chemotherapy drugs kill fast-growing cells, including myeloma cells. Chemotherapy drugs can be given through a vein in your arm or taken in pill form. High doses of chemotherapy drugs are used before a bone marrow transplant.

Biological therapy: Biological therapy drugs use your body's immune system to fight myeloma cells. The drugs thalidomide (Thalomid), lenalidomide (Revlimid) and pomalidomide (Pomalyst) enhance the immune system cells that identify and attack cancer cells. These medications are commonly taken in pill form.

Targeted therapy. Targeted drug treatment focuses on specific abnormalities within cancer cells that allow them to survive. Bortezomib (Velcade), carfilzomib (Kyprolis) and ixazomib (Ninlaro) are targeted drugs that block the action of a substance in myeloma cells that breaks down proteins. This action causes myeloma cells to die. Targeted-therapy drugs may be administered through a vein in your arm or in pill form.

Other targeted-therapy treatments include monoclonal antibody drugs that bind to the specific proteins present on myeloma cells, causing them to die.

Corticosteroids: Corticosteroids, such as prednisone and dexamethasone, regulate the immune system to control inflammation in the body. They are also active against myeloma cells. Corticosteroids can be taken in pill form or administered through a vein in your arm.

Team Of Consultants

Dr. Dharma Choudhary

Dr.Dharma Choudhary

Director - BLK Centre for Bone Marrow Transplant

Dr.Dharma Choudhary

Director - BLK Centre for Bone Marrow Transplant
Dr Rahul Bharqava

Dr. Rahul Bhargava

Director & head - Fortis Hospital, Gurgaon

Dr. Rahul Bhargava

Director & head - Fortis Hospital, Gurgaon
Dr. Sunil Kumar Gupta

Dr. Sunil Kumar Gupta

Director & HOD - Venkateshwar Hospital, Delhi

Dr. Sunil Kumar Gupta

Director & HOD - Venkateshwar Hospital, Delhi
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