Treatments

These medications can be divided into five major categories:

Proteasome inhibitors (PIs)^[3]

In a normal cell, proteins are broken down by a small structure known as a ‘proteasome’. This acts like a waste bin where used proteins are recycled. Cancer cells, which have increased metabolism, use these proteasomes very intensively to keep functioning, and by inhibiting its function this will eventually lead to myeloma cell death.

Immunomodulators (IMiDs)^[3][4]

These medicines have a direct effect on cancer cells, and they also regulate certain parts of the immune system. They can activate certain immune cells and prevent certain types of growth signals for cancer cells. By 'modulating' the immune system in this way, they use the body’s own defence mechanisms against the cancer.

Monoclonal antibodies (mAbs)^[3]

These antibodies are used as immunotherapy to activate the body's own immune system to eliminate cancer cells. These antibodies are highly targeted, attaching to particular proteins located on the surface of the tumour cells. As a result, the immune system recognises these cells and they are attacked. Some of the mAbs may also exert direct anti-myeloma cell activities, killing the malignant cells.

Corticosteroids^[3][5]

These have long been used in myeloma treatment due to their ability to kill myeloma cells in high doses. They are often used in combination with other anti-myeloma medicines.

Histone deacetylase (HDAC) inhibitors^[3]

These kill cells by interfering with specific enzymes, weakening the genetic structures of cancer cells.

Antibody-drug conjugates (ADCs)^[6]

Antibodies that are attached to an anti-cancer drug or a therapeutic agent, with a linker, are used to search for and enter cancer cells. Once inside these cancer cells, the anti-cancer drug is released where it can prevent their growth and can also cause cell death. In addition, the antibodies themselves can activate the body’s immune system to further help eliminate cancer cells.

Selective inhibitor of nuclear export (SINE)^[7]8

Overexpression of a protein called exportin 1 (XPO1) has an important role in helping cancer cells to survive – it is also associated with poorer treatment outcomes. SINEs block the activity of the XPO1 protein, which can prevent growth of cancer cells and can also lead to cancer cell death.

These medicines are administered either orally or intravenously (through a drip). They aim to kill cancer cells.^[3] A key drug used in this context is melphalan, which is given orally and is generally tolerated quite well.⁹ Melphalan is also used as part of autologous transplantation, but in this context it is administered at a high dose intravenously.¹⁰

In this type of transplantation, the stem cells come from another person: a compatible donor – usually a brother or sister. Allogenic transplants aim to use the immune system of the donor to help fight the patient's myeloma.

However, these transplants are associated with risks. The most significant are that you will get an infection or that your body tissues will react badly to the transplanted cells from the donor.

One issue with chemotherapy is that when given in high doses it destroys stem cells in the bone marrow. These are the cells that go on to develop into blood cells, and are therefore essential for maintaining good health. A solution is to collect a sample of stem cells from a patient before high-dose chemotherapy, so that they can be given back to them afterwards. Because it's the patient's own cells being given back to them, it is called an 'autologous' stem cell transplant.

CAR-T cell therapy is a type of immunotherapy that helps the immune system to fight cancer including multiple myeloma. T cells are a type of white blood cell and part of the immune system responsible for attacking foreign cells in the body. During CAR-T therapy, some of the body's own T cells will be collected then be reprogrammed in a lab to become CAR-T cells. The CAR-T cells are then reintroduced into the patient's body through an infusion so they can recognise and attack the multiple myeloma cells.