Multiple Myeloma

Multiple Myeloma

Multiple myeloma is a type of cancer that develops due to an increase in the number of abnormal plasma cells. The plasma cells are a type of blood cells that are present in the bone marrow. The bone marrow is a spongy area present inside the bone.

Plasma cells produce antibodies when the body is attacked by an infection from bacteria or viruses. These antibodies are called Immunoglobulins. Immunoglobulins can be of five types depending on their features. These are named as IgA, IgD, IgE, IgM and IgG. These immunoglobulins are made up of two main parts called as light chains and heavy chains. The heavy chains are five types, A, G, D, M, and E as above and the light chains are of two types, lambda and kappa.

When a myeloma develops in the body, the abnormal plasma cells usually produce one of the immunoglobulins in excess. This in turn leads to reduced production of other cells in the bone marrow such as red blood cells, other white blood cells and platelets. The reduced number of other blood cells and increased levels of plasma cells and abnormal immunoglobulins leads to development of symptoms and complications from myeloma. The myeloma can also cause destruction of the bones in different parts of the body causing pain and fractures and affect other organs in the body such as the kidenys.


Increasing age is a risk factor for myeloma like it is for many other cancers. Myeloma is more common after the age of 65.


MGUS or monoclonal gammopathy of undetermined significance is a condition where there is excess of paraprotein(immunoglobulin) in the blood. Some patients who have this condition can develop a myeloma over a period of time. MGUS itself does not cause any symptoms and is usually found by chance when tests are done for other reasons.

Radiation Exposure

Exposure to radiation at work or other areas can increase the risk of developing a myeloma.

Reduced Immune system

Reduced immunity in the body due to some drugs or medical conditions such as HIV/AIDS can increase the risk of developing a myeloma.

Increased weight

Increased weight and obesity have been linked to an increased risk of developing a myeloma

Auto immune disease

Having certain conditions called autoimmune diseases increases the risk of developing a myeloma

Myeloma can produce a number of symptoms depending on the organs affected in the body.

Symptoms due to low blood counts

When there is presence of myeloma in the bone marrow, it can cause a reduction of normal blood cells such as red blood cells, white blood cells and platelets. As a result of that the patient can have symptoms due to anaemia if the red blood cells are low, bleeding and bruising due to low platelets and infections due to low white blood cells.


Myeloma spreads to the bones in the body and causes destruction and weakening of the bones. This can lead to the pain in the affected area and increases the risk of fractures of the bones.

Increased Calcium

Myeloma can cause an increased level of calcium in the blood which can cause symptoms such as tiredness, increased thirst, dehydration, constipation, vomiting and confusion.

Kidney damage

Myeloma proteins can accumulate in the kidneys and cause renal failure. This can lead to leg swelling, breathlessness, tiredness and other symptoms.

Other symptoms

Other symptoms from myeloma include fatigue, tiredness, reduced appetite and weight, confusion, dizziness, headaches, muscle weakness, numbness and paralysis.

The following tests are done when a myeloma is suspected in a patient. This will help establish the diagnosis, classify the type of myeloma and know the extent of disease.

Blood Tests

A number of blood tests are done to look for or diagnose Myeloma. The common tests done are listed such as complete blood picture (CBP), kidney function tests, liver function tests (LFT), ESR, Calcium level and others.

Serum Electrophoresis and Immunofixation

This is a type of blood test that looks for elevated levels of paraprotein or immunoglobulins. Serum immunofixation identifies the exact nature of the elevated paraprotein.

Serum free light chain essay

This test is done to look for the presence of light chains in the blood when light chain myeloma is suspected.

B2 Microglobulin

This is a marker present in the blood and is elevated in patients with myeloma. This test can be used to diagnose myeloma as well as to monitor the response of the disease to treatment and help in diagnosis of myeloma.

Urine tests

A urine sample is tested for the presence of abnormal protein to aid in diagnosis of myeloma.

Bone marrow biopsy

A bone marrow biopsy is done to confirm the diagnosis of myeloma. The bone marrow is examined to calculate the number of plasma cells and 10% or more of plasma cells in it are needed usually to make a diagnosis of myeloma.


Samples from the bone marrow biopsy are also tested for changes in the genetic material in the cells which can help in predicting the possible outcomes of the condition after treatment.

X-rays and scans

x-rays of the bones are done to look for deposits of myeloma in the bones. This type of test is called a skeletal survey. If a scan is done such as a CT scan or a PET-CT scan, then a skeletal survey may not be needed. These tests help in making a diagnosis of myeloma and showing the extent of disease in the body.

Myeloma is due to abnormal production of immunoglobulins. Immunoglobulins are made up of heavy chains and light chains. The heavy chains are of different types named as G, M, D, A, and E.

An IgG myeloma is the commonest of these and will contain a high level of the immunoglobulin IgG. The other types of heavy chain myelomas are not as common.

Active Myeloma

This is the myeloma that is one that is active and produces symptoms. For a patient to be diagnosed as having myeloma, they need to have any of these features

More than 10% plasma cells in the bone marrow
Damage of organs such as kidney leading to kidney failure
Presence of myeloma lesions in the bones (osteolytic lesions)
Abnormal blood cells causing anaemia, bleeding or raised calcium level

Light chain Myelomas

The light chains consist of kappa and lambda and light chain myelomas may produce either kappa or lambda chains. Light chain myelomas do not produce entire immunoglobulins.

Non secreting Myelomas

Some myelomas do not produce large amounts of immunoglobulins which can be detected in the blood or urine are known as non secreting myelomas.

Monoclonal gammopathy of unknown significance (MGUS)

This is a condition where there is an increase in the number of plasma cells or immunoglobulins(paraprotein) but the increase is not high enough to make a diagnosis of myeloma. In this situation, the patient is under close follow up by the doctor. A small proportion of patients will develop into a myeloma over a course of some years.

Smouldering Myeloma

This is a situation where a diagnosis of myeloma is made but there is no evidence of any damage from the myeloma to the organs in the body. In this situation, it is possible to adapt a wait and watch approach and treat only when there is an increase of the myeloma. Smouldering myeloma can be divided into low risk, intermediate and high risk.


A solitary plasmacytoma is a condition where there is tumour made up of plasma cells present in the bone or the soft tissues in the body. It is different from a myeloma in not being present in the bone marrow and marrow containing less than 10% plasma cells. In some instances, multiple solitary plasmacytomas are also seen. A plasmacytoma is treated differently to a myeloma. A proportion of patients with plasmacytoma can go on to develop a myeloma over the course of time.

Myeloma is staged based on the International staging system (ISS), revised ISS (R-ISS) and the Durie-Salmon staging system. The ISS staging system is listed below and is based on the level of Beta 2 microglbulin (B2M) and serum albumin levels and should be used only in symptomatic myeloma.

Stage 1- B2M level less than 3.5 mg/l and serum albumin equal to or more than 3.5gm/dl

Stage 2- Neither stage 1 nor stage 3

Stage 3- B2M equal to or more than 5.5mg/l

Treatment options of myeloma vary depending on the extent of disease, the organs involved and the age and fitness of the patient.

Wait and watch approach

In patients with low risk smouldering myeloma or asymptomatic myeloma, a wait and approach can be used where treatment is not given and the patient is closely monitored every 3-6 months. Treatment is started once the patient starts to develop any symptoms from myeloma or the disease progresses where symptoms could start soon.

Induction Therapy

Once a myeloma is diagnosed, the doctor will consider giving induction therapy. This treatment is aimed at controlling the disease that is present. Induction therapy can be in the form of different combinations of drugs which can include chemotherapy, biological agents, steroids and other drugs. These are selected based on the condition of the patient and the availability of drugs. The duration of induction therapy can range from 3-6 months depending on whether high dose therapy and stem cell transplant are being considered later and how the cancer is responding to the treatment.

At the time of induction therapy, patients are divided into transplant eligible or ineligible. Those that are considered eligible are given the option of having high dose chemotherapy followed by stem cell transplant. The details are given below. Commonly, two or three drugs are combined to produce the best effect in induction treatment. The combination of drugs include steroids, chemotherapy and biological therapy. Common treatments used as induction therapy in

Transplant eligible patients includes-

  • Thalidomide or Lenalidomide and Dexamethasone
  • Cyclofosfamide, Bortezomib and Dexamethasone
  • Bortezomib and Dexamethasone
  • Thalidomide Bortezomib and Dexamethasone

In transplant ineligible patients, induction treatments include-

Above regimes as well as those containing Melphalan such as

  • Bortezomib, Lenalidomide and Prednisolone
  • Melphalan and Prednisolone

Maintenance Therapy

Following completion of induction therapy, in patients that do not have a stem cell transplant, maintenance treatment can be considered. This will involve continuation of treatment after induction therapy. Maintenance treatment is also used after completion of a stem cell transplant. Common drugs used for maintenance therapy include Bortezomib, Lenalidomide, Thalidomide or steroids. This treatment is usually in the form of a single drug given at regular intervals.


Chemotherapy is used either alone on in combinations with steroids and biological agents for treatment of myeloma. Common chemotherapy agents used in this condition include Cyclofosfamide, melphalan, Doxorubicn and Idarubicin. Some of the combinations are listed here.

Cyclofosfamide, Thalidomide and Dexamethasone (CTD)

Doxorubicin, Bortezomib, Dexamethasone (PAD)


Steroids are normally produced in the body and have various functions in the body. In cancer, they are used to reduce inflammation and they are used commonly to treat myeloma. In myeloma, they have a direct effect on killing cancer cells. They are used alone or usually in combination with chemotherapy or biological therapy. Steroids used in this setting are Dexamethasone, Prednisolone or methyl prednisolone. Steroids are given as tablets or as a drip through the vein and are given to be taken daily or on certain days of the treatment cycle.

Biological Agents

Biological agents or targeted therapies are drugs that target specific areas on or in the cancer cell to stop it from growing or to kill it. These agents are commonly used in the treatment of myeloma. They are used alone or in combination with steroids and chemotherapy. Commonly used agents include

  • Thalidomide
  • Lenalidomide
  • Bortezomib

Bortezomib is a drug belonging to the group of drugs called Proteasome inhibitors. Proteasomes help the cancer cell to grow and progress and these drugs stop the mechanism. Bortezomib is given as an injection through the vein or under the skin.

Carfilzomib and Ixazomib are newer proteasome inhibitors also used to treat myeloma that do not respond to other treatments.

Thalidomide and Lenalidomide are immunomodulating agents used in the treatment of myeloma. They also have antiangiogenic properties which stop the formation of new blood vessels that the cancer needs to grow and progress. These drugs are given as tablets.

High dose therapy and stem cell transplant

This is a form of treatment that is considered in patients at the stage of completion of induction therapy or at a time when the myeloma has come back after initial treatment. This treatment involves giving high dose of chemotherapy to kill off all the blood cells in the blood and bone marrow. This aims to kill off any myeloma cells also present in the body. Following that, stem cells which are collected before high dose chemotherapy are infused back into the patient and these cells go on to form new blood cells in the patient. This treatment is not suitable for all patients and is dependent on factors such as age, fitness and status of the myeloma.

The function of the bone marrow normally is to produce blood cells such as red blood cells which help the blood to carry oxygen, white blood cells which protect against infections and platelets which help stop bleeding. A significant lowering of these cells in the blood is dangerous to the patient and hence a transplant of these cells is needed after a high dose of chemotherapy.

Collection of Stem Cells

Stem cells are a type of blood cells that have the capacity to develop into any kind of blood cell such as red blood, white blood cell or platelets. These stem cells are present in the blood stream and bone marrow and are initially collected from the patient before the patient receives high dose chemotherapy. This process of collection of stem cells from the patient and infusing them back into the same patient after high dose chemotherapy is called as Autologous Stem cell transplant.

If the stem cells are from another person(donor), then it is called an Allogenic stem cell transplant. The donor can be related, usually a brother or a sister, or unrelated but matched donor. A donor may be used in situations when there is cancer present in the marrow or an Autologous transplant was done before, but the disease has relapsed again.

Before collection of stem cells, the patient may have chemotherapy and injections with G-CSF which will increase the number of stem cells in the blood to achieve a successful collection.

On the day of collection of stem cells, the patient is connected to a machine and the patient’s blood is taken out from one vein and it passes through the machine to collect the stem cells present in the blood. The blood then passes back into the patient through another vein. This process is done over a few hours.

Once the stem cells are collected, the patient receives the high dose chemotherapy. After the chemotherapy, the stem cells are infused back into the patient. These cells go into the bone marrow and start making blood cells again.

Stem cell transplant is more commonly used these days as compared to bone marrow transplant.

Collection of bone marrow

Bone marrow is the spongy material that is present inside the bones. For a bone marrow transplant, the marrow needs to be collected prior to giving high dose chemotherapy. The procedure to collect the marrow is done under general anaesthesia usually in an operation theatre. The marrow may be taken out from different places in the bones and about 1 litre of it may be taken out at the procedure. Once taken out, it is stored and infused into the patient when needed.

Risks and side effects of Stem cell and Bone marrow Transplant

Having a stem cell or bone marrow transplant is a complex process and is associated with side effects. This procedure usually involves staying in hospital for a few weeks for the blood cells in the marrow and blood to recover to normal levels after the transplant is done. Common side effects associated with this procedure include

Nausea, Vomiting, Hair loss, altered function of the liver are potential side effects of this treatment.

Risk of Infection as white blood cells are low and the patient to prone to get an infection. The infections could be bacterial, viral or fungal and will usually need antibiotics to control them.

Mucositis is due to the effect of chemotherapy on the inside lining of the mouth and digestive tract. This can limit the amount of food taken by the patient and other methods of feeding may be used in that instance.

Bleeding is a risk associated with this procedure due to low platelet count, but platelet transfusion can be given to keep the platelet counts up.

Graft versus host disease This is a reaction of the body to the transfused cells particularly if the stem cells or marrow is from a donor.


Radiotherapy uses high energy x-rays to kill cancer cells. In myeloma, radiotherapy is used to treat symptoms such as pain that is due to presence of disease in the bones or other parts of the body. Usually 1-5 treatments are given and is quite effective in controlling pain.

Treatment of Recurrent or relapsed myeloma

The treatment of myeloma that has come back after initial treatment depends on the location of the relapse, the symptoms of the patient, prior treatments received by the patient and the current fitness of the patient. Treatment options include chemotherapy, biological therapy, radiotherapy and supportive care.

Other treatments

Blood transfusion, platelet transfusion etc may be needed in situations when there is anaemia or low platelets due to disease or treatment.

Treatment of Solitary Plasmacytoma

A solitary plasmacytoma is a localised area of collection of plasma cells that over time can become a myeloma. A solitary plasmacytoma can be in the bones or in the soft tissues of the body. All tests for myeloma are necessary to exclude the presence of a myeloma before a diagnosis of solitary plasmacytoma is made.

As this condition is usually localised to one area of the body, local treatments are preferred to others such as chemotherapy. Sometimes a surgical removal is done of the entire area as part of the diagnostic process. Usually only a biopsy is done to get the diagnosis along with other tests.

Radiotherapy is a commonly used treatment used for control of plasmacytoma. The radiotherapy here is given once a day for 4-5 weeks duration with the aim being to get rid of the disease completely.

Following completion of treatment, the patient is followed up in the clinic to look for any development of myeloma over a period of time.