Ipilimumab and nivolumab

Ipilimumab and nivolumab is the name of a combination of immunotherapy treatments.

You pronounce ipilimumab as ih-pih-lih-moo-mab. You pronounce nivolumab as ni-vol-you-mab.

They are a treatment for a number of different cancer types.

How does ipilimumab and nivolumab work?

Ipilimumab and nivolumab are types of immunotherapy called a checkpoint inhibitor. They are also described as a type of monoclonal antibody  or targeted treatment .

Checkpoint inhibitors work by blocking certain proteins that stop the immune system  from working properly and attacking cancer cells. They help to make your immune system find and kill cancer cells. 

Ipilimumab blocks the protein called CTLA-4 (cytotoxic T lymphocyte associated protein 4). Nivolumab blocks a protein called PD-1 (programmed cell death protein 1).

How do you have ipilimumab and nivolumab?

You have ipilimumab as a drip into your bloodstream (intravenously).

You have nivolumab intravenously or as an injection under the skin (subcutaneously).

Into your bloodstream

You might have treatment through a long plastic tube that goes into a large vein in your chest. The tube stays in place throughout the course of treatment. This can be a:

• central line
• PICC line
• portacath

If you don't have a central line

You might have treatment through a thin short tube (a cannula) that goes into a vein in your arm. You have a new cannula each time you have treatment.

Injection under your skin (subcutaneous injection)

You usually have an injection under the skin (subcutaneous injection) into the stomach or thigh over about 3 to 5 minutes.

The area might be painful, sting or you may have a dull ache for a short time after this type of injection, but it doesn't usually hurt much. The skin in the area may go red, itchy or swollen for a while.

How often do you have ipilimumab and nivolumab?

You have ipilimumab and nivolumab as cycles of treatment. This means that you have the drugs and then a rest to allow your body to recover.

Each cycle varies depending on what type of cancer you have. Your doctor or nurse will tell you more about this.

Tests

You have blood tests before and during your treatment. They check your levels of blood cells and other substances in the blood. They also check how well your liver, kidneys and thyroid gland are working.

Before treatment starts you may have a blood test to check for viruses such as hepatitis B, hepatitis C, and HIV . This is called a viral screen.

It’s important for your doctor to know if you have had any of these viruses. This is because this treatment can weaken your immune system and can cause the virus to become active again (reactivation). 

What are the side effects of ipilimumab and nivolumab?

Side effects can vary from person to person. They also depend on what other treatment you are having. 

When to contact your team

Your doctor, pharmacist or nurse will go through the possible side effects. They will monitor you closely during treatment and check how you are at your appointments. Contact your advice line as soon as possible if:

• you have severe side effects

• your side effects aren’t getting any better

• your side effects are getting worse

Early treatment can help manage side effects better. 

We haven't listed all the side effects here. Talk to your healthcare team if you have any new symptoms that you think might be a side effect of your treatment.

Remember it is very unlikely that you will have all of these side effects, but you might have some of them at the same time.

Common side effects

These side effects happen in more than 10 in 100 people (more than 10%). You might have one or more of them. They include:

Increased risk of infection

Increased risk of getting an infection is due to a drop in white blood cells. Symptoms include a change in temperature, aching muscles, headaches, feeling cold and shivery, and generally unwell. You might have other symptoms depending on where the infection is.

Less commonly you might get an infection in your lungs that could affects your breathing. Symptoms can include a cough, breathlessness, wheeze, chest pain and a sore throat.

This treatment can cause an infection of your water works, but this is rare. This is also called a urinary tract infection or UTI. Symptoms include difficulty peeing, you may go often or suddenly. It might look cloudy, be painful, burn or sting when you pee. 

Infections can sometimes be life threatening. You should contact your advice line urgently if you think you have an infection. 

Breathlessness and looking pale

You might be breathless and look pale due to a drop in red blood cells. This is called anaemia.

Bruising, bleeding gums or nose bleeds

This is due to a drop in the number of platelets in your blood. These blood cells help the blood to clot when we cut ourselves. You may have nosebleeds or bleeding gums after brushing your teeth. Or you may have lots of tiny red spots or bruises on your arms or legs (known as petechiae).

Changes to thyroid levels

It is common with this treatment that your thyroid hormone levels may drop. Less commonly your thyroid levels might get too high. Or you might have inflammation of the thyroid.

Symptoms can include feeling tired or having too much energy, you may gain or lose weight. You may sweat more than usual. You may feel anxious, nervous, irritable, or have mood swings or a fast pounding heartbeat.

Let your healthcare team know of any changes. Your may have medicine to control your thyroid levels. You may need to have them for a long time or for life.

Loss of appetite

You might lose your appetite for various reasons while having cancer treatment. Sickness, taste changes or tiredness can put you off food and drinks.

Changes in blood sugar levels

You might get changes to your blood sugar levels. Symptoms of high blood sugar levels are feeling very thirsty, a dry mouth, and passing urine very often. You may feel tired, blurred vision, weight loss, feeling or being sick, and fruity smelling breath.

Or you might get low blood sugar levels. These symptoms include sweating, feeling hungry, shaky or trembling. You may get a fast heartbeat, dizziness, changes to your mood and feeling tired.

Less commonly you might develop diabetes .

Headaches

Tell your healthcare team if you keep getting headaches. They can give you painkillers to help.

Dizziness

This treatment might make you feel dizzy. Don’t drive or operate machinery if you have this.

Difficulty breathing or a cough

It is important to tell your doctor or nurse if you have a cough or feel breathless. You might have lung problems such as inflammation or fluid around the lungs.

Diarrhoea

Contact your advice line if you have diarrhoea. For example, in one day you have 2 or more loose bowel movements than usual. If you have a stoma , you might have more output than normal. Your doctor may give you anti diarrhoea medicine to take home with you after treatment.

Try to eat small meals and snacks regularly. It’s best to try to have a healthy balanced diet if you can. You don’t necessarily need to stop eating foods that contain fibre. But if your diet is normally very high in fibre, it might help to cut back on high fibre foods such as beans, nuts, seeds, dried fruit, bran and raw vegetables. 

Drink plenty to try and replace the fluid lost. Aim for 8 to 10 glasses per day.

Constipation

Constipation is easier to sort out if you treat it early. Drink plenty and eat as much fresh fruit and vegetables as you can. Try to take gentle exercise, such as walking. Tell your healthcare team if you think you are constipated. They can give you a laxative if needed.

Feeling or being sick

Feeling or being sick is usually well controlled with anti sickness medicines. It might help to avoid fatty or fried foods, eat small meals and snacks and take regular sips of water. Relaxation techniques might also help.

It is important to take anti sickness medicines as prescribed even if you don’t feel sick. It is easier to prevent sickness rather than treat it once it has started.

Pain in different parts of the body

You might feel some pain in your bones, muscles, joints or tummy. Less commonly you might feel like there is pressure, heaviness, tightness, or squeezing across your chest.

Tell your doctor or nurse so they can find the cause and give you medicine to help.

Skin problems

Symptoms of skin problems can include a rash and itching.

You might have areas of pale white patches on the skin (vitiligo), or an itchy bumpy rash (hives). Your skin might be dry or red. These symptoms happen less often.

Rarely you can get a severe skin reaction. This may start as tender red patches which leads to peeling or blistering of the skin. You might also feel feverish, and your eyes may be more sensitive to light. This is serious and could be life threatening.

Your skin might develop patches that are raised, red, flaky and crusty (psoriasis). There may also be silvery or grey scales that form. Or you might develop red spots that might be itchy. They may start on your legs or arms but sometimes on your face or other parts of the body.

Very rarely patches of skin may be itchy, painful, white, cracked or smooth. They can get damaged and bleed easily. This is called lichen sclerosis and can happen anywhere on the body. But it mainly affects the genitals .

Tiredness and weakness

Tiredness and weakness (fatigue) can happen during and after treatment. Doing gentle exercises each day can keep your energy up. Don't push yourself, rest when you start to feel tired and ask others for help.

Tell your team if you feel tired and weak, you may need a blood test to check your hormone levels.

High temperature (fever)

Tell your healthcare team straightaway if you get a high temperature. Ask them if you can take paracetamol to help lower your temperature.

Fluid build up

A build up of fluid also known as oedema. This treatment may cause swelling in your arms, hands, ankles, legs, face and other parts of the body. Contact your healthcare team if this happens to you.

Liver changes

It is common with this treatment to have liver changes that are usually picked up on tests. You have regular blood tests to check for any changes and they usually go back to normal when treatment finishes.

Less commonly this treatment can cause inflammation of the liver. Symptoms may include muscle, joint or tummy pain. You may feel or be sick, feel tired or weak, and have a high temperature. You can lose your appetite and the whites of the eyes or skin may go yellow. You may also have dark coloured pee.

Let your healthcare team know if you develop any symptoms.

Kidney changes

This treatment can cause changes in the way your kidneys work. This is usually picked up in tests. You have regular blood tests to check for any changes.

Less commonly your kidneys might stop working. Rarely you may have inflammation of the kidneys.

Symptoms of kidney problems can include high blood pressure, feeling or being sick. You may not pee enough and feel confused. You may get swelling of your legs, ankles and feet.

Let your healthcare team know if you have any symptoms.

Problems with the pancreas

The pancreas is a gland that produces digestive juices and hormones. 

It is common to have high levels of substances (enzymes) called amylase and lipase in your blood. These are responsible for breaking down fat and starch.  

Less commonly this treatment can cause inflammation of your pancreas. Symptoms of this can include severe tummy pain, feeling or being sick, a high temperature or you may have loose poo.

Let your healthcare team know if you have symptoms. They will do regular blood tests to check how well the pancreas is working.

Changes in the levels of substances in your body

Your blood contains different minerals, electrolytes and proteins.

This treatment can commonly cause changes to the levels of calcium, sodium and potassium in your blood.

Less commonly it might affect the levels of magnesium, albumin and phosphate.

You have regular blood tests during treatment to check this.

Occasional side effects

These side effects happen in between 1 and 10 out of every 100 people (between 1 and 10%). You might have one or more of them. They include:

• a reaction to the drug – you might get a rash, shortness of breath, redness or swelling of the face, and dizziness. Tell your healthcare team straight away if this happens
• a reaction to the drug during or shortly after, causing your immune system to make a large amount of cytokines . Symptoms include fever, chills, a headache, difficulty breathing and dizziness
• inflammation of the airways in the lungs (bronchitis) - symptoms include cough, chest pain, breathlessness, sore throat, runny nose and high temperature
• your adrenal glands might stop working properly, this can make you feel tired, sick or dizzy. You may need medicine such as steroids . If they stop working suddenly you can feel very ill and will need medical attention. Call your healthcare team straight away
• pituitary gland problems that can cause fatigue, feeling generally weak, joint pain, vision problems, and headaches
• lack of fluid in your body (dehydration)
• weight loss
• numbness or tingling in the hands and feet
• eye problems including dry eyes or blurred vision. You might get an infection that can make your eyes feel gritty, itchy, sticky from pus, watery and look red. Rarely you might get inflammation of the eyes causing redness and pain
• heart problems – your heartbeat might get faster or become irregular. Less commonly you might have inflammation or build up of fluid around the heart. Rarely you might get inflammation of the heart muscle or a slower heart beat. Symptoms of heart problems include chest pain or tightness, shortness of breath even when you are resting, fever and generally feeling unwell. Call your advice line if you have any of these symptoms 
• high blood pressure - symptoms include headaches, nosebleeds, blurred or double vision or shortness of breath. You have your blood pressure checked regularly
• a blood clot in your lung (pulmonary embolism) – call 999 or go to A&E if you have pain in your chest or upper back, difficulty breathing or cough up blood
• inflammation of the bowel – this can cause diarrhoea with or without blood or pus, tummy pain or cramps, tiredness, and problems having a poo
• your mouth might be dry, sore and develop ulcers
• inflammation of the stomach lining – symptoms can include tummy pain, indigestion, feeling or being sick, feeling full or you may burp or fart
• hair thinning or hair loss
• shivering or shaking (chills)
• inflammation or swelling of your joints (arthritis)
• muscle problems such as spasms or weakness. Rarely your muscle can get inflamed causing pain, tenderness and stiffness
• high levels of a type of white blood cell called eosinophils in your blood

Rare side effects

These side effects happen in fewer than 1 in 100 people (less than 1%). You might have one or more of them. They include:

• inflammation of tissues covering the brain and spinal cord (aseptic meningitis) - symptoms might include fever, headaches, neck pain or stiffness, feeling or being sick or sensitivity to light
• long term problems caused by inflammation in some organs and tissues. The most common site is the lungs (sarcoidosis)
• a build up of a substance called ketones in the blood - symptoms include feeling very thirsty, being sick, passing urine more than usual, and passing out
• the parathyroid gland not producing enough parathyroid hormones causing low calcium levels. Symptoms include a tingling feeling in your fingers and toes, muscle cramps particularly in your legs. Your skin looks and feels dry and you feel generally weak
• imbalance of substances in your blood (metabolic acidosis). Syptoms can include confusion, tiredness, shortness of breath, and headaches
• inflammation or damage to nerves causing numbness and weakness, tingling or burning pain
• swelling in the brain
• difficulty lifting your foot or toes
• the immune system attacking the nervous system. This is known as Guillain-Barre syndrome. It can cause numbness, weakness and pain in the body
• inflammation of the spinal cord - your arms and legs may be painful, numb, tingle or feel weak. It can affect your bladder and bowel. You may lose control of when you pee and poo or it may change how frequently you go
• inflammation of the small bowel
• a tear in the bowel wall (perforation)
• coeliac disease
• a problem with the parts of the body that produce fluids, like tears and spit (Sjögren's syndrome)
• damage to muscle tissue releasing certain substances into the blood
• inflammation of the bladder can make you want to go for a pee more often or you may have a strong need to pee immediately

Other side effects

There isn't enough information to work out how often these side effects might happen. You might have one or more of them. They include:

• a condition when your immune system makes too many white blood cells causing inflammation and damages tissues of the body. Symptoms can include a high temperature and rash. Your spleen , liver or lymph nodes maybe swollen
• your immune system treating an organ transplant like a foreign body. This means your body could reject the organ
• changes to the levels of chemicals in your blood due to the breakdown of tumour cells - you have regular blood tests to check for this

Coping with side effects

We have more information about side effects and tips on how to cope with them.

What else do you need to know?

Other medicines, foods and drink

Cancer drugs can interact with medicines, herbal products, and some food and drinks. We are unable to list all the possible interactions that may happen. An example is grapefruit or grapefruit juice which can increase the side effects of certain drugs.

Tell your healthcare team about any medicines you are taking. This includes vitamins, herbal supplements and over the counter remedies. Also let them know about any other medical conditions or allergies you may have.

Pregnancy and contraception

It is unknown whether treatment may or may not harm a baby developing in the womb. It is important not to become pregnant or get someone pregnant while you are having treatment. Let your team know straight away if you or your partner become pregnant while having treatment.

Talk to your doctor or nurse about effective contraception you can use during treatment. Ask how long you should use it before starting treatment and after treatment has finished.

Loss of fertility

It is not known whether this treatment affects fertility in people. Talk to your doctor before starting treatment if you think you may want to have a baby in the future.

Breastfeeding

It is not known whether these drugs come through into the breast milk. Doctors usually advise that you don’t breastfeed during this treatment.

Treatment for other conditions

If you are having tests or treatment for anything else, always mention your cancer treatment. For example, if you are visiting your dentist.

Immunisations

Don’t have immunisations with live vaccines while you’re having treatment and for up to 12 months afterwards. The length of time depends on the treatment you are having.

Ask your doctor or pharmacist how long you should avoid live vaccinations.

In the UK, live vaccines include rubella, mumps, measles, BCG, and yellow fever.

You can usually have:

• other vaccines, but they might not give you as much protection as usual
• the flu vaccine (as an injection)
• the coronavirus (COVID-19) vaccine

Talk to your doctor or pharmacist about the best time to have a vaccine in relation to your cancer treatment.

Contact with others who have had immunisations 

You can be in contact with other people who have had live vaccines as injections. If someone has had a live vaccine by mouth or nasal spray there may be a small risk the vaccine virus can be passed onto you if your immune system is weakened.

Your healthcare team will let you know if you need to take any precautions if you are in close contact with someone who has had a live vaccine.

More information

For further information about each drug and the possible side effects go to the electronic Medicines Compendium (eMC) website. You can find patient information leaflets for each drug on this website.

You can report any side effect you have to the Medicines Health and Regulatory Authority (MHRA) as part of their Yellow Card Scheme.