New myeloma drugs and clinical studies

What is bendamustine?

Bendamustine is a type of chemotherapy drug called an alkylating agent and is very similar to melphalan which is used widely in myeloma.

How does bendamustine work?

Bendamustine works by damaging the DNA in myeloma cells. DNA is the genetic material within cells that tell the cell what to do – for example, to grow and multiply.

Damaging the DNA prevents the repair, replication and multiplication of the myeloma cells and results in their death.

How is bendamustine given?

It is given by intravenous infusion over 30 - 60 minutes.

What are the potential side-effects of bendamustine?

Its side-effects are similar to other alkylating chemotherapy drugs and may include:

• Low blood counts
• Fatigue
• Constipation
• Nausea

Side-effects should resolve once treatment is stopped.

What is denosumab?

Denosumab is a type of monoclonal antibody being looked at in clinical studies in a variety of clinical conditions associated with loss of or thinning of bones including myeloma.

How does it work?

Myeloma bone disease results from the myeloma cells in the bone morrow affecting the surrounding bone. Usually, the bones undergo a continuous cycle of bone remodelling where old bone is removed (or resorbed) by osteoclast cells and new bone is formed by osteoblast cells.

This process occurs in equilibrium so that the rate of old bone resorption is equal to the rate at which new bone is formed. When myeloma cells are present in the bone marrow, the myeloma cells stimulate osteoclast production and reduce the number of osteoblasts. This results in a net loss of bone, i.e. more bone is resorbed than is formed.

Denosumab acts on the osteoclasts and inhibits their ability to break bone down, meaning less bone loss due to myeloma bone disease.

How is it given?

Denosumab is given by injection under the skin (subcutaneous), usually in the thigh or stomach.

What are the potential side-effects of denosumab?

The side-effects are similar those of bisphosphonates and may include:

• Fever and flu-like symptoms
• Localised irritation
• General bone aches and pains
• Nausea

Denosumab but may also include increased risk of infection. The incidence of jaw problems (osteonecrosis of the jaw (ONJ) is thought to be less with denosumab than with the bisphosphonates.

What is pomalidomide?

Pomalidomide is an immunomodulatory drug (IMiD) which is a derivative of thalidomide and similar to lenalidomide (Revlimid®).

How does it work?

Pomalidomide is an immunomodulatory drug. This means that it works by modifying your immune system. The main function of the immune system is to fight disease and infection.

Pomalidomide has been shown to have many mechanisms of action that may affect myeloma cell survival. However, the exact method by which myeloma cells are killed in an individual patient is not fully understood.

How is it given?

Pomalidomide comes in capsule form and it taken orally.

What are the potential side-effects of pomalidomide?

Pomalidomide can have an effect on unborn babies. There is a strict risk management programme in place to ensure that this is prevented and everyone taking pomalidomide will be asked to ensure that they use reliable contraception.

Other side-effects of pomalidomide may include:

• Drowsiness
• Constipation
• Rash
• Muscle cramps
• Fatigue
• Increased risk of developing blood clots or deep vein thrombosis (DVT)

Pomalidomide can also lower blood counts; this will be monitored regularly each time a blood sample is taken.

Unlike Revlimid and thalidomide, pomalidomide is not thought to cause peripheral neuropathy.

What is carfilzomib?

Carfilzomib is a proteasome inhibitor which is similar to, but potentially more potent than, Velcade®.

How does it work?

Carfilzomib is a proteasome inhibitor which targets part of the myeloma cell that is responsible for breaking down waste products. This is different to the way chemotherapy works. When the proteasome is blocked, the myeloma cannot remove waste products from the cell and this will cause it to die.

How is it given?

It is given by intravenous injection, which lasts approximately 3 - 5 seconds.

What are the potential side-effects of carfilzomib?

Carfilzomib has been shown to be generally well-tolerated in clinical studies; however it does have some potential side-effects which may include:

• Fatigue
• Low blood counts
• Nausea, vomiting or a reduced appetite

Unlike Velcade, it is not thought that carfilzomib will cause peripheral neuropathy.