This information has been prepared to help you understand more about checkpoint immunotherapy, a treatment offered to some people with cancer. We hope this information will help you, your family and friends understand how immunotherapy may help treat cancer .
What it is and how it works
Immunotherapy is a type of drug treatment that uses the body’s own immune system to fight cancer. It is different to chemotherapy, which works by killing cancer cells.
Different types of immunotherapy work in different ways. Some stimulate the immune system so it works better against cancer. Others remove barriers that stop the immune system attacking the cancer.
Checkpoint immunotherapy is currently available in Australia for some types of cancer.
Immunotheraphy has worked well for some people, but it does not help everyone.
When immunotherapy is used
Surgery, chemotherapy and radiation therapy are still the main treatments for many cancers but some people with particular types of cancer may benefit from checkpoint immunotherapy.
To work out if checkpoint immunotherapy is suitable for you, your cancer specialist will consider the type and stage of cancer, your treatment history, your future treatment options and your overall health. Even if immunotherapy is recommended as a treatment, it is difficult to predict whether it will work. The rate of success varies depending on the type of cancer (see box below).
So far, most people who have been treated with checkpoint immunotherapy have had advanced cancer. This means either the cancer has come back and spread after the initial treatment, or it was at an advanced stage when they were first diagnosed. For particular cancer types, such as melanoma, immunotherapy is starting to become available for earlier stage cancers.
About the immune system
The immune system protects the body from infections. When a foreign organism such as a germ enters the body, or when a cell becomes abnormal, the immune system usually recognises and then attacks it so that it doesn’t harm the body. This process is called an immune response.
The immune system can remember every germ or abnormal cell it has attacked so it can easily recognise it if it enters the body again.
The parts of the immune system
The immune system is made up of a network of cells, chemicals, tissues and organs. White blood cells known as lymphocytes are part of the immune system. They travel throughout the body looking for germs and abnormal cells. There are two main types of lymphocytes:
- B-cells – make proteins called antibodies. An antibody can lock onto the surface of the invading germ. This helps T-cells recognise the germ.
- T-cells – recognise and destroy germs and abnormal cells. T-cells also help control and direct the activity of the immune system.
The organs of the immune system help to make, filter and process lymphocytes. These are some of the major organs of the immune system:
- bone marrow – the spongy material inside bones
- lymph nodes – small structures found in groups throughout the body and linked by lymph vessels
- spleen – a large organ in the abdomen
- thymus – a gland behind the breastbone
- tonsils – two small organs at the back of the throat.
Cancer and the immune system
Cancer starts when abnormal cells begin growing out of control. The immune system usually prevents cancers from developing because it recognises abnormal cells and destroys them. In some cases, the natural immune response is not strong enough to kill all abnormal cells and they develop into cancer.
Cancer cells also find ways to stop the immune system destroying them – for example, by setting up barriers (“checkpoints”) so the immune system can’t reach them, or by changing over time (mutating) to avoid being recognised by T-cells and antibodies.
Conditions affecting immune response
It is important to tell your cancer specialist if you have an autoimmune disease such as rheumatoid arthritis or lupus or if you’ve had an organ transplant. You may still be able to have immunotherapy, but it could be more difficult. Autoimmune diseases make the body’s immune system overactive so it attacks normal cells, leading to symptoms such as inflammation, swelling and pain. The extra immune system activity caused by immunotherapy can make these symptoms worse. After an organ transplant, most people take drugs that suppress the immune system to stop the body rejecting the new organ. Your specialists will need to carefully balance these drugs with the extra immune system activity caused by immunotherapy.
How checkpoint immunotherapy works
The drugs known as checkpoint inhibitors are the most widely used form of immunotherapy for cancer. They work by helping the immune system to recognise and attack the cancer.
There are challenges when you have checkpoint immunotherapy as part of your cancer treatment, including gaining access to it as well as common and rare side effects. Scroll down for more information on accessing immunotherapy and side effects.
Other types of immunotherapy
There are other types of immunotherapy. A few are available now as approved treatment for cancer, but most are still being tested in clinical trials and may be more widely available in future.
Some treatments are used to stimulate the immune system to attack the cancer. These are known as immune stimulants.
In non-muscle-invasive bladder cancer, the vaccine Bacillus Calmette-Guérin (BCG) may be used as an immune stimulant. It is given into the bladder through a catheter. The BCG stimulates the immune system to stop or delay bladder cancer coming back or becoming invasive.
In some types of skin cancers, a cream called imiquimod is applied directly to the affected area to stimulate a local immune response.
Adoptive cell transfer
This experimental type of immunotherapy is used to boost the ability of T-cells to fight cancer. Chimeric antigen receptor (CAR) T-cell therapy is a type of adoptive cell transfer that is being tested in Australian clinical trials. It is showing good results for some types of leukaemia and lymphoma.
In CAR T-cell therapy, the T-cells are removed from the blood, and a new gene is introduced into the T-cells to enable them to recognise cancer cells. The T-cells are then returned to the blood by an intravenous drip (infusion). The altered T-cells multiply and trigger a number of immune responses that attack the cancer cells.
These viruses directly infect tumour cells and cause an immune response against the infected cells. An oncolytic virus therapy known as talimogene laherparepvec or T-VEC (brand name Imlygic) is sometimes used for melanoma. It is injected directly into the melanoma both to kill the melanoma cells and to stimulate the immune system to attack melanoma cells.
Oncolytic virus therapies for brain cancer and some other types of cancer are being tested in clinical trials, but the research is still in its early stages.
How vaccines help prevent cancer
Vaccines help train the immune system to prevent some types of cancer. The human papillomavirus (HPV) vaccine is used to prevent cervical cancer, and it is hoped it will also prevent anal and penile cancers and some cancers of the head and neck. Vaccines against hepatitis B and hepatitis C viruses help prevent liver cancer.
How immunotherapy differs from other cancer treatments
Immunotherapy works in a different way from other cancer treatments and has different side effects. Chemotherapy, radiation therapy, surgery and targeted therapy are four other forms of cancer treatments.
Chemotherapy uses drugs to kill or damage rapidly dividing cells anywhere in the body. It can work for many types of cancer because cancer cells divide rapidly. Chemotherapy also damages healthy cells that divide rapidly, such as hair follicles, blood cells and cells inside the mouth and bowel. This can cause a range of side effects, such as nausea, fatigue, hair loss, and low white blood cell counts (making you more prone to infections). Unlike cancer cells, normal cells can recover, so most side effects are temporary.
Radiation therapy uses targeted radiation (usually x-ray beams) to kill or damage cancer cells so they cannot grow, multiply or spread. The treatment focuses on a specific area at a time and is most effective when the cancer has not spread to other parts of the body. It can also be used to treat symptoms such as pain. Radiation therapy can cause fatigue, as well as side effects at or near the treatment site (e.g. skin problems, nausea, bowel problems).
Surgery removes cancer from a specific area of the body. This can be effective if the cancer is found before it has spread to other parts of the body. However, surgery on its own is rarely able to treat cancer that has spread. The main side effects of surgery are pain and risk of infection.
uses drugs to attack specific features of cancer cells, known as molecular targets, that are causing the tumour to grow uncontrollably. While targeted therapy is designed to affect only the cancer cells, it can still cause side effects in some people.
As researchers learn more about cancer, treatments change. Immunotherapy is not a new idea, but older types were less effective. Checkpoint immunotherapy is having better results in some cancers. Like all treatments, checkpoint immunotherapy sometimes causes side effects. The extra activity of the immune system can cause inflammation anywhere in the body, leading to a variety of possible side effects, such as skin rash, diarrhoea and breathing problems (scroll down for more on side effects).
The challenges of immunotherapy
You may have several questions and concerns about having immunotherapy. There have been media reports of how immunotherapy is a “miracle drug” and how it can cure cancer. This means that people’s expectations can be very high when starting treatment, or they may be confused and upset if they aren’t offered immunotherapy as part of their treatment.
Effectiveness of immunotherapy
The most challenging issue is that checkpoint immunotherapy doesn’t work for everyone. If you are thinking about trying immunotherapy, ask your cancer specialist how likely you are to respond to the treatment and what other treatments are available. To make immunotherapy available to more people in the future, researchers are trying to understand why some people respond better than others.
Length of treatment
Like most other cancer treatments, checkpoint immunotherapy usually takes a while to work, so you and your family may experience anxiety waiting to see whether you’ll respond to the treatment. If it does work, you may worry about how long immunotherapy will control the cancer or whether the cancer will come back.
These uncertainties can make it challenging to make plans about work, relationships and travel. Many people find comfort in everyday activities; others focus on doing things they’ve always wanted to do. Let your cancer nurse or specialist know how you’re feeling. They may recommend seeing a psychologist to help you work through your thoughts.
Cancer Council also has more information on coping with uncertainty.
If immunotherapy doesn’t work or stops working, ask your cancer specialist about your other treatment options. You may be able to try another type of immunotherapy drug or join a clinical trial.
The cost of immunotherapy
The cost of checkpoint immunotherapy drugs is high (often several thousand dollars per dose).
As at June 2019, the Australian Government covers most of this cost for some types of advanced cancer through the Pharmaceutical Benefits Scheme (PBS). Reimbursement for some other types of cancer may be added in the future. Your specialist can give you the latest information.
| Advanced cancer type
|| Checkpoint inhibitors available on the PBS*
|pembrolizumab (brand name Keytruda)
|head and neck cancer
||nivolumab (Opdivo), ipilimumab (Yervoy)
||pembrolizumab (Keytruda), nivolumab (Opdivo), atezolizumab (Tecentriq)
||pembrolizumab (Keytruda), nivolumab (Opdivo), ipilimumab (Yervoy)
|Merkel cell carcinoma
|| * As at June 2019
When your drug is not on the PBS
You may be able to access checkpoint immunotherapy through clinical trials or, sometimes, through a compassionate access program or cost-share program offered by the pharmaceutical company.
Some people choose to make significant financial decisions to cover the costs of immunotherapy for cancers that are not on the PBS. Before deciding to pay for these drugs, it is important to fully understand the financial costs, as well as the possible risks and benefits for your type of cancer. Take the time to discuss these questions with your cancer specialist and your family.
How immunotherapy is given
Checkpoint immunotherapy is usually given directly into a vein through an intravenous drip. Sometimes two checkpoint inhibitor drugs are given together, or a checkpoint inhibitor drug is given with a chemotherapy or targeted therapy drug.
You will usually have checkpoint immunotherapy as an outpatient, which means you visit the hospital or treatment centre for the day. You may have treatment every two to four weeks in a repeating cycle.
How often and how long you have the treatment depends on several factors:
- the type of cancer and how advanced it is
- the type of checkpoint inhibitor/s; how you respond to treatment
- what side effects, if any, you experience.
Many people stay on immunotherapy for up to two years, but clinical trials are now testing if the treatment can be given for a shorter period of time once it has started working or whether ongoing treatment is necessary.
Because immunotherapy drugs act directly on the body’s own immune system, how long they keep working will vary from person to person. Sometimes, they keep working long after treatment stops.
Side effects of immunotherapy
Checkpoint immunotherapy can cause side effects anywhere in the body. These are different to the side effects of other cancer treatments and need to be managed differently. The side effects of immunotherapy are sometimes called immune-related adverse effects (IRAEs).
The diagram below shows some possible side effects of immunotherapy. You may have side effects within days of starting treatment, but more commonly they occur many weeks or months after starting treatment. In some rare cases, new side effects can appear months after treatment.
Managing side effects
Because immunotherapy works differently from other cancer treatments, it’s important to work closely with your treatment team to monitor your response.
Before starting immunotherapy, discuss the potential side effects with your cancer specialist. They can give you a Consumer Medicine Information leaflet about the immunotherapy drug that you are having. Ask which side effects to watch out for or report, and who to contact after hours. Throughout treatment, the team will regularly test your blood and ask you questions to check for early signs of side effects.
Because new side effects can appear months after having immunotherapy, ask your cancer specialist how long you need to look out for side effects.
Reporting side effects
Side effects can be better managed if reported early. If left untreated, side effects can become serious and may even be life-threatening.
It is important to let your cancer care team know about new or worsening symptoms, even if they seem minor or you’re not sure if they are related to your treatment.
Because immunotherapy is still a new cancer treatment, general practitioners (GPs) and other health professionals may not yet be familiar with the side effects. Your team may give you a card with information about your immunotherapy treatment and potential side effects. You can give this card to any other health professionals you see and ask them to consult with your cancer specialist.
Do not start any new medicines, including anti-inflammatory steroids, until your cancer specialist has been consulted. If you become unwell, even years later, it is important to tell any health professionals you see that you have had immunotherapy.
Treating side effects
Side effects will be graded on a scale of 1 to 4 to help decide how to treat them.
- Moderate to severe side effects (grades 2–4) are often treated with steroid tablets, such as prednisone.
- In some cases of severe side effects (grades 3–4), people may be hospitalised and/or treated with intravenous steroids or other medicines. Immunotherapy may need to be stopped until the side effects are better controlled.
If side effects become too severe, immunotherapy must be stopped permanently. In this case, the immunotherapy that you have already received may have “trained” the immune system to recognise cancer cells, so you may continue to benefit.
Although there is a risk of severe side effects, it may be reassuring to know that many people experience only mild side effects.
Checking whether the immunotherapy is working
You will have regular check-ups with your cancer specialist, blood tests and different types of scans to check whether the cancer has responded to treatment.
It may take some time to know if immunotherapy has worked because some people have a delayed response. Rarely, the cancer may appear to get worse before improving.
You may wonder whether having side effects means the treatment is working. Immunotherapy side effects do indicate that the treatment is affecting your immune system in some way, but the link with treatment success is unclear. Many people who have had no side effects have still seen improvements in the cancer.
Sometimes it can be tricky to know which of your symptoms may be related to the cancer and which may be side effects of the immunotherapy. Make sure to discuss this with your cancer care team.
A good response from immunotherapy will make the cancer shrink. In some cases, the cancer remains stable, which means it doesn’t increase in size on scans but also does not shrink or disappear. People with stable disease can continue to have a good quality of life.
When immunotherapy doesn’t work
Unfortunately, immunotherapy does not work for everyone, and some people who have immunotherapy will not respond to the treatment. This can be very disappointing, but your cancer specialist will help you explore other treatment options if this happens.
Ask your cancer specialist if immunotherapy is a suitable treatment for you and whether it is reimbursed through the PBS for your type of cancer. It may be possible to access immunotherapy treatments through clinical trials. Speak with your treatment team for more information.
- Is immunotherapy available as part of my treatment plan. If not, why not? Would other treatment options be better for me?
- How do I find out about clinical trials? Are there any nearby that might be right for me?
- What do you expect the immunotherapy to do to the cancer?
- What percentage of people with this type of cancer respond to immunotherapy?
- Which immunotherapy are you recommending?
- Will it be my only treatment, or will I also have other treatments?
- How often will I receive immunotherapy? Can you give me the Consumer Medicine Information for it?
- How long will I have treatment?
- Where will I have treatment?
- What side effects should I watch out for or report?
- Who do I contact if I get side effects?
- How can side effects be managed?
- How will I know if the treatment is working?
- How much will immunotherapy cost?
- Can I take my other medicines while having immunotherapy? Can I have the flu vaccine?
The internet has many useful resources, although not all websites are reliable. These websites are good sources of information.
Expert content reviewers:
by: A/Prof Brett Hughes, Senior Staff Specialist, Medical Oncology, Royal Brisbane and Women’s Hospital and The Prince Charles Hospital, and Associate Professor, The University of Queensland, QLD; Dawn Bedwell, 13 11 20 Consultant, Cancer Council Queensland, QLD; Tamara Dawson, Consumer; A/Prof Craig Gedye, Senior Staff Specialist, Medical Oncology, Calvary Mater Newcastle, and Conjoint Associate Professor, School of Medicine and Public Health, University of Newcastle, NSW; A/Prof Alexander Menzies, Medical Oncologist, Associate Professor of Melanoma Medical Oncology, and Faculty Member, Melanoma Institute Australia, The University of Sydney, Royal North Shore Hospital and Mater Hospital, NSW; Dr Donna Milne, Nurse Consultant Melanoma and Skin Service, Peter MacCallum Cancer Centre, VIC; Dr Geoffrey Peters, Staff Specialist, Medical Oncology, Canberra Hospital and Health Services, and Clinical Lecturer, Australian National University, ACT.