Checkpoint Inhibitors

Checkpoint inhibitors are a type of immunotherapy. These drugs block different proteins called checkpoint proteins that stop the immune system from attacking the cancer cells. They are a treatment for several cancers including melanoma skin cancer and lung cancer.

You might also hear them named after the checkpoint proteins they block. For example, CTLA-4 inhibitors, PD-1 inhibitors and PD-L1 inhibitors. 

Cancer drugs do not always fit easily into a certain type of treatment. This is because some drugs work in more than one way and belong to more than one group.

Checkpoint inhibitors are also described as a type of monoclonal antibody or targeted treatment.

How do checkpoint inhibitors work?

Our immune system protects us from disease, killing bacteria and viruses. One main type of immune cell that does this is called a T cell.

T cells have proteins on them that turn on an immune response and other proteins that turn it off. These are called checkpoint proteins.

Some checkpoint proteins help tell T cells to become active, for example when an infection is present. But if T cells are active for too long, or react to things they shouldn’t, they can start to destroy healthy cells and tissues. So other checkpoints help tell T cells to switch off.

Some cancer cells and T cells make high levels of proteins. These can switch off T cells, when they should really be attacking the cancer cells. So the cancer cells are pushing a stop button on the immune system. And the T cells can no longer recognise and kill cancer cells.

Drugs that block checkpoint proteins are called checkpoint inhibitors. They stop the proteins on the cancer cells or T cells from pushing the stop button. This turns the immune system back on and the T cells are able to find and attack the cancer cells.

Below is a short video that explains how checkpoint inhibitors work. The video lasts 1 minute.

Types of checkpoint inhibitors

These drugs block different checkpoint proteins. The names of these proteins include:

• PD-1 (programmed cell death protein 1)

• CTLA-4 (cytotoxic T lymphocyte associated protein 4)

• PD-L1 (programmed cell death ligand 1)

• LAG-3 (lymphocyte activation gene 3)

CTLA-4, PD-1, and LAG-3 are found on T cells. PD-L1 are on cancer cells.

PD-1

Checkpoint inhibitors that block PD-1 include:

• nivolumab (Opdivo)

• pembrolizumab (Keytruda)

• cemiplimab (Libtayo)

Nivolumab and pembrolizumab are treatments for a number of different cancer types including:

• melanoma skin cancer

• Hodgkin lymphoma

• non small cell lung cancer (NSCLC)

• kidney cancer

• head and neck cancers

• bowel cancer

• stomach cancer

• bile duct cancer

Pembrolizumab is also a treatment for people with cancer of the:

• breast

• cervix

• womb

Cemiplimab is a treatment for people with a type of skin cancer called advanced cutaneous squamous cell carcinoma (SCC).

CTLA-4

Ipilimumab (Yervoy) is a checkpoint inhibitor drug that blocks CTLA-4. It is a treatment for advanced melanoma and advanced renal cell cancer.

You might have ipilimumab with a PD-1 inhibitor such as nivolumab. This combination is for some people with:

• melanoma skin cancer

• advanced kidney cancer

• mesothelioma

• bowel cancer

• NSCLC

PD-L1

Checkpoint inhibitors that block PD-L1 include:

• atezolizumab
• avelumab
• durvalumab

Atezolizumab is a treatment for:

• lung cancer
• liver cancers
• breast cancers
• urothelial bladder cancer

Avelumab is a treatment for a type of skin cancer called merkel cell carcinoma (MCC). You might also have avelumab if you have:

• kidney cancer
• urothelial bladder cancer

Durvalumab is a treatment for NSCLC and bile duct cancer.

LAG-3

Relatlimab is a LAG-3 checkpoint inhibitor. It is available mixed together with nivolumab. The is called Opdualag. It is a new treatment for people with advanced melanoma who are 12 years or older.

When you might have these drugs

Ask your doctor if these drugs are suitable for you. Whether you can have this treatment depends on your type of cancer. It might also depend on:

• the stage of your cancer

• whether you have already had certain treatments

To find out if you can have some checkpoint inhibitors your doctor needs to check the surface of cancer cells. They are looking for checkpoint proteins such as PD-L1.

To test your cancer cells, doctors need a sample of your cancer. They may be able to use a sample from a biopsy or operation you have already had.

This testing does not apply to all checkpoint inhibitors. Your doctor or specialist nurse can tell you if this applies to you.

How do you have checkpoint inhibitors?

You usually have these drugs as a drip into your bloodstream. You might have atezolizumab as an injection under the skin (subcutaneous injection).

What are the side effects of checkpoint inhibitors?

All treatments can cause side effects. While there are general side effects for a type of treatment, they vary for each individual drug and from person to person. The side effects can also depend on what other treatments you’re having.

Checkpoint inhibitor drugs boost all the immune cells, not just the ones that target cancer. This may cause inflammation in different parts of the body which can cause serious side effects. They could happen during treatment, or some months after treatment has finished. In some people, these side effects could be life threatening.

Some of the general side effects of checkpoint inhibitors include:

• skin problems such as rashes, dry and itchy skin

• diarrhoea  

• inflammation of the digestive system 

• tiredness (fatigue)

• feeling or being sick 

• loss of appetite

• breathlessness and a dry cough, caused by inflammation of the lungs 

• an allergic reaction to the drug that can cause a rash, shortness of breath, redness or swelling of the face and dizziness

Checkpoint inhibitors can also affect the liver, kidneys and hormone making glands (such as the thyroid). You have regular blood tests to check for this.

Your medical team will talk through the possible side effects of your treatment. This is so you know what to look out for and when to contact them. Tell your doctor or nurse if you have any side effects so they can treat them as soon as possible.