Myeloma

What is Multiple Myeloma?

Multiple myeloma is a cancer arising from abnormal growth of plasma cells. Plasma Cells are a normal component of the bone marrow which is produced from B lymphocytes. They are responsible for producing IMMUNOGLOBULINS, which are proteins produced to fight infections. In multiple myeloma, collections of abnormal plasma cells accumulate in the bone marrow, where they interfere with the production of normal blood cells.

Types of Multiple Myeloma

Multiple Myeloma(MM) is classified based on the type of Immunoglobulin heavy /light chain it produces. This can be

• IgG (Commonest)
• IgA
• IgM
• IgD

The light chain is either Kappa or Lamda. 25% of cases produce light chains only. These are called PARAPROTEIN and they compromise the production of normal immunoglobulins.

What are the Symptoms of Multiple Myeloma?

The symptoms of myeloma are abbreviated as CRAB:

• C- Increase in calcium levels in blood causing weakness, fatigue, sleepiness, headache and constipation.
• R- Renal or Kidney abnormalities. This happens when there is excess production of light chains clogging the tubules in the kidneys.
• A Anemia due to replacement of normal bone marrow cells.
• B- Bone involvement. This is the cardinal symptom of MM resulting in severe back or rib pain often resulting in fracture of the backbone, hip or other bones without any trauma.

Other signs and symptoms of multiple myeloma may include:

• Repeated infections — such as pneumonia, sinusitis, bladder or kidney infections, skin infections and shingles
• Weight loss
• Weakness or numbness in legs

What are the causes and risk factors of Multiple Myeloma?

Although the exact cause isn't known, doctors do know that multiple myeloma begins with one abnormal plasma cell in the bone marrow - the soft, blood-producing tissue that fills in the center of most of bones. This abnormal cell then starts multiplying.

Some factors that may increase the risk of multiple myeloma include:

• Age: Older age - 60 and above.
• Sex: Men are more likely to develop the disease than are women.
• Race: Blacks are about twice as likely to develop multiple myeloma as are whites.
• History of a monoclonal gammopathy of undetermined significance (MGUS).
• Obesity
• High exposure to radiation
• Working in petroleum-related industries.

How do we Diagnose Myeloma?

• Complete Blood Count: The characteristic finding of MM is often anemia with a raised ESR.
• Bone Marrow Examination: This is necessary for confirmation of the diagnosis. There must be more than 10% of abnormal plasma cells (Blasts) in the bone marrow to call it a MM.
• Serum Protein Electrophoresis and Serum Free Light Chain Assay: This is essential for diagnosis of Myeloma, which detects abnormal immunoglobulin as a M BAND or disproportionate increase in one of the light chains.
• Flow Cytometry: is often essential to differentiate MGUS from Myeloma.
• Cytogenetics: This is testing for abnormalities in the chromosomes.

Several chromosomal abnormalities such as 17pdel or 13q deletc are associated with poor prognosis.

Staging of Multiple Myeloma

Multiple Myeloma goes through 3 stages

• MGUS (Monoclonal Gammopathy of Uncertain Significance): This is diagnosed when a patient is found to have an abnormal immunoglobulin in small amounts without any symptoms or involvement of any organs.
• Indolent Myeloma: This is diagnosed when the diagnostic workup fulfils the criteria of MM but the patient is asymptomatic.
• Symptomatic Myeloma: when along with the above the patient is symptomatic.

How do we classify Multiple Myeloma to decide on the outcome?

There are two systems by which we prognosticate MM. One is Durie-Salmon system and the other is International Staging System.

How do we treat Multiple Myeloma?

Autologous BMT is the standard of care for a newly diagnosed Multiple Myeloma after the disease is brought under control by 4-6 cycles of chemotherapy.

The following are treatment options for active multiple myeloma. The types of treatments given are based on the unique needs of the person with cancer.

Chemotherapy and other drug therapy - Chemotherapy is given as the primary treatment for active multiple myeloma. Chemotherapy is often combined with a corticosteroid.

Chemotherapy is usually given in 3 phases:

• Induction therapy
• Consolidation therapy
• Maintenance therapy

Stem cell transplant - Stem cell transplant may be offered for active multiple myeloma following high-dose chemotherapy.

Radiation therapy

External beam radiation therapy may be given as the primary treatment for a single tumour in the bone (plasmacytoma) causing symptoms, such as bone pain. External beam radiation therapy may be used to prevent a fracture in a diseased bone. It may also be given to treat fractures or spinal cord compression.

Supportive therapy

Supportive therapy to prevent or control health problems and complications related to active multiple myeloma includes:

• Growth factors – help in the production of new red blood cells to treat anemia
• Bisphosphonates – slow down bone destruction, which causes weakened bones and kidney problems
• Antibiotics – treat or help to prevent infection
• plasmapheresis – treat increased thickening (hyperviscosity) of the blood

Extramedullaryplasmacytoma

Extramedullaryplasmacytoma is a unique type of multiple myeloma that is treated differently from multiple myeloma that affects the bone. Extramedullaryplasmacytomas start outside the bone marrow (extramedullary) in soft tissues of the body. The main types of treatment for an extramedullaryplasmacytoma are:

• Radiation therapy
• Surgery to remove the tumour

Relapsed and refractory multiple myeloma

Relapsed disease means the cancer has come back after treatment. Refractory disease means the cancer is resistant (does not respond) to the first or most recent treatment given.

Both relapsed and refractory multiple myeloma may require further treatment to control the disease. Treatment options for people with relapsed or refractory multiple myeloma includes:

• Watchful waiting (for people whose disease is stable)
• Chemotherapy (including targeted chemotherapy)
• Corticosteroids
• Stem cell transplant
• Supportive therapy

Bone Marrow Transplantation (BMT) for Multiple Myeloma

When is BMT needed for Multiple Myeloma?

The best results are obtained if Autologous BMT is carried out upfront. Even if BMT is carried out later, the PBSC should be collected within the first 6 months of good response. Otherwise, mobilisation of PBSC becomes difficult.

How is Conditioning for Autologous BMT done in Multiple Myeloma?

High dose Chemotherapy is generally used in conditioning for BMT.

Is Autologous BMT curative for Multiple Myeloma?

Generally not, however, this gives a prolonged period of good quality life not requiring any treatment. This can vary from 1-10 years. The best results are obtained, if a patient achieves a proper Complete Remission after BMT.

What happens after relapse following Autologous BMT?

The patients have to be monitored closely. Once the paraprotein rises sharply or the Autologous BMT patient becomes symptomatic, treatment is warranted.

• If the relapse occurs after many years (at least > 2 years), the patient responds to further treatment and a second Autologous BMT.
• If the patient relapses early or more than once, an ALLOGENEIC BMT should be considered?

Why is Allogeneic BMT not considered early in Multiple Myeloma as in Acute Leukemia?

The results of Autologous BMT are very good and result in virtually no mortality. Hence, Allogeneic BMT is reserved for patients after relapse.

Who can be a donor for Allogeneic BMT?

Although we prefer a matched family donor, a Half matched (Haploidentical) family donor or an unrelated cord blood are suitable alternatives.

What are the results of Allogeneic BMT in Multiple Myeloma?

This is the only curative treatment for Myeloma. However, it is very difficult to eradicate Multiple Myeloma completely. The newer drugs and a sequential approach of Autologous BMT, further treatment and/or Allogeneic BMT results in patients of Multiple Myeloma surviving over a decade and some of them are indeed cured.

What is Minimal Residual Disease?

Minimal Residual Disease (MRD) means patient still has a minimum disease and has not fully recovered. Response to treatment is conventionally defined by the number of blasts we see under the microscope. If we see less than 5% such cells it is called COMPLETE REMISSION (CR).However, CR means that the number of leukemia cells in the body are less than 109 or 1000 million cells. Further treatment which spans over months of intensive treatment and years of oral treatment are geared to reduce the number of leukemia cells to a level where our immune system can eliminate the remaining cells.

MRD is the detection of cells below 1%, which can range of 1 in 1000 to 1 in a million cells. This enables us to monitor the effect of treatment and change it, if needed.