Leukaemia

Biological therapies - targeted cancer drugs for leukaemia

Biological therapies - targeted cancer drugs are derived from, or target substances that occur naturally in the body. They have been designed or modified in the laboratory to attack or control particular types of cancer cells. Because they are targeted, they have a different mechanism of action compared to traditional “cytotoxic” chemotherapy, and side effects like hair loss are less common. Targeted cancer drugs may be used together with other treatments for various kinds of leukaemia but for chronic myeloid leukaemia (CML) it is used alone as first line treatment.

Tyrosine Kinase Inhibitors (TKIs)

Tyrosine Kinase Inhibitors block the action of enzymes called tyrosine kinases. These enzymes may be too active or found at high levels in some types of leukaemia, and blocking them may help keep cancer cells from growing.

Imatinib (Glivec)

In CML, the uncontrolled multiplication of white blood cells is a caused by a growth signal (tyrosine kinases) being permanently switched to “on”. The biological drug imatinib (Glivec) attacks the growth signal, stopping the uncontrolled growth, producing remission. Following development and clinical trials during the 1990s, imatinib came into routine use in Britain in 2002, revolutionising the treatment and prognosis of CML. People we spoke to had been among the first to have it in the UK. Some initially had it in a clinical trial and continued taking it afterwards. Another woman obtained the drug outside a trial but before it was routinely used in the NHS.

Imatinib (Glivec) is taken daily as a single capsule or tablet, or four smaller tablets. Most people took it with their evening meal to avoid nausea. Having felt sick after taking it in the mornings, one woman preferred to take it at bedtime. Most people had few or mild side-effects, but Elizabeth at first reacted badly to the drug, was hospitalised and had to stop and restart it repeatedly before achieving remission (see ‘Unwanted effects of treatments’).
Imatinib is also used as a treatment for people with Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph+ ALL) and has improved the prognosis of these patients when it is combined with chemotherapy. Bone marrow transplant remains the recommended treatment for this disease.

Other Tyrosine Kinase Inhibitors for CML
There are other Tyrosine Kinase Inhibitors that are similar to imatinib (Glivec); dasatinib (Sprycel) and nilotinib (Tasigna), and can be given when people with CML do not respond, become resistant to imatinib or have too many side effects on imatinib. Ponatinib (Iclusig) or bosutinib (Bosulif) are newer Tyrosine Kinase Inhibitors that target different proteins. You might have these drugs as part of a clinical trial or through the Cancer Drugs Fund. 

B-cell signalling inhibitors
In chronic lymphocytic leukaemia (CLL) the cells have proteins on the outside called B-cell receptors (BCRs). When a protein binds to a BCR it sends a signal to the cell to survive. CLL cells are very sensitive to BCR signals, which means the bone marrow produces too many and these fill up the bone marrow and stop it from producing normal healthy cells. B-cell signalling inhibitors block or inhibit the survival signal in CLL cells, allowing them to be die more quickly. Ibrutinib (Imbruvica) and Idelalisib (Zydelig) are B-cell signalling inhibitors used in the treatment of CLL.

Monoclonal antibodies - Immunotherapy
The body makes antibodies in response to infection, enabling the immune system to recognise infections it has met before and deal with them quickly. Monoclonal antibodies made in a laboratory can recognise particular types of cancer cells and make the immune system attack them. Types of monoclonal antibodies used for leukaemia are rituximab (Rituxan), alemtuzamab (Campath 1H), gemtuzumab (Mylotarg), ofatumumab (Arzerra), obinutuzumab (Gazyvaro).

Rituximab 
This targets a protein called CD20 on the surface of B lymphocytes (a type of white blood cell) and destroys them. It is given intravenously and is used mainly to treat non-Hodgkin’s lymphoma but now also CLL in combination with chemotherapy (FCR). Rituximab may also be used to treat B-cell ALL.One man with chronic lymphocytic leukaemia (CLL) was given it after his lymphocytes attacked his red blood cells causing them to break down (haemolysis). This autoimmune haemolytic anaemia (AIHA) is a complication of CLL. Later he received another monoclonal antibody, alemtuzumab, as part of preparation for a stem cell transplant.

Glyn was given alemtuzumab after his CLL had not responded to chemotherapy. He went to hospital three days each week and initially was given the drug intravenously, then by injection under the skin (subcutaneously).

Gemtuzumab (Mylotarg) is a combination of a monoclonal antibody and a chemotherapy drug. The ending '-mab' in the name indicates that it is a monoclonal antibody. It attaches to a protein on the surface of leukaemia cells thereby destroying them without harming normal cells. Some people with acute myeloid leukaemia (AML) were given gemtuzumab (Mylotarg) as part of a clinical trial. 

Lenalidomide (Revlimid)
Lenalidomide can block the growth of blood vessels and so prevent cancers spreading. It is a new drug whose action is not fully understood and it is not routinely used in leukaemia, but it is used in myeloma, another form of bone marrow cancer. Glyn’s doctors applied to the then local Primary Care Trust for permission to give him lenalidomide after chemotherapy and antibody therapy had not worked. The drug is taken as capsules at home and Glyn had a slight upset stomach at first. He had no other side effects and his CLL is now in remission.

Vaccines
Vaccines have long been used to stimulate the immune system to fight bacteria and viruses and they are now being developed to fight cancer cells in the same way. Elizabeth heard about a trial in the USA of a vaccine to be taken alongside imatinib (Glivec) and got permission from her doctors to take part. She paid for her travel to America but once there the drug company covered all expenses. She had some of her CML cells harvested to tailor the vaccine to her disease before receiving nightly injections of the vaccine. Her white blood cell count dropped temporarily but then rose again.

Tretinoin (Vesanoid; ATRA)
This drug is a form of vitamin A. It is given alongside chemotherapy to people with a type of AML called acute promyelocytic leukaemia (APML). It helps the leukaemic cells to mature normally. Side effects are common but it may be difficult to distinguish them from those caused by chemotherapy.

“It’s important not to become pregnant or father a child while taking ATRA, as it may harm the developing baby. It’s important to use effective contraception while taking this drug, and for at least a few months afterwards. Your doctor or nurse will discuss this with you. If you’re already pregnant, ATRA shouldn’t be given if you’re less than 12 weeks pregnant. After 12 weeks, it can be given safely. It’s usually given without chemotherapy, as this is safer for the baby and still effective." (Macmillan Cancer Support 2018) 

*CML – Chronic myeloid leukaemia

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Last reviewed: December 2018.
Last updated: December 2018.

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