Nivolumab and relatlimab (Opdualag)

Opdualag is made up of 2 immunotherapy drugs. You pronounce Opdualag as op-doo-uh-lag. It is a treatment for melanoma skin cancer that either:

• can’t be removed with surgery (unresectable melanoma)
• has spread to other parts of the body (metastatic melanoma)

How does Opdualag work?

Opdualag is made up of the immunotherapy drugs nivolumab and relatlimab. You pronounce nivolumab as ni-vol-you-mab. And relatlimab as reh-lat-lih-mab.

Nivolumab and relatlimab are types of immunotherapy called checkpoint inhibitors. They block proteins that stop the immune system attacking cancer cells.

Checkpoint inhibitors block different proteins. Nivolumab blocks a protein called PD-1 (programmed cell death protein 1). And relatlimab blocks a protein called LAG-3 (lymphocyte activation gene 3).

How do you have Opdualag?

The 2 immunotherapy drugs in Opdualag are already mixed together. You have it as a drip into your bloodstream (intravenously).

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.

How often do you have Opdualag?

You have Opdualag every 4 weeks. Each treatment takes about 30 minutes.

You can have Opdualag for up to 2 years as long as it is working and you are not experiencing too many side effects.

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 and kidneys are working.

What are the side effects of Opdualag?

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, cough, headaches, feeling cold and shivery, pain or burning feeling when weeing, or generally feeling unwell. You might have other symptoms depending on where the infection is.

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.

Fatigue

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.

Joint or muscle pain

You might feel some pain from your muscles and joints. Speak to your doctor or nurse about what painkillers you can take to help with this.

Rarely you may get rheumatoid arthritis or a condition called polymyalgia rheumatica. This causes pain and stiffness in your hips, shoulders and neck.

Skin problems

Skin problems include a skin rash, dry skin and itching. This usually goes back to normal when your treatment finishes. Your healthcare team can tell you what products you can use on your skin to help.

You might also have patchy changes in your skin colour (vitiligo). Less often your skin might be very sensitive to sunlight.

Rarely you might get inflammation where the hairs on your skin grow, blisters or dry flaky patches of skin.

Diarrhoea

Contact your advice line if you have 4 loose watery poos (diarrhoea) or more in 24 hours. Or if you have diarrhoea for more than 3 days. Or if you can't drink to replace the lost fluid. 

Also, call if you have blood or mucus in your poo, your poo looks darker than usual, or if you develop pain in your tummy (abdomen).

You can help to prevent worsening your diarrhoea by eating less fibre, avoiding raw fruits, fruit juice, cereals and vegetables, and drinking plenty to replace the fluid lost.

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.

Headaches

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

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.

Cough or difficulty breathing

You might develop a cough or breathing problems. This could be due to inflammation of the lungs (pneumonitis).

Let your doctor or nurse know straight away if you suddenly become breathless or develop a cough.

Decreased appetite and weight loss

You might not feel like eating and may lose weight. Eating several small meals and snacks throughout the day can be easier to manage. You can talk to a dietitian if you are concerned about your appetite or weight loss. 

Changes in the levels of thyroid hormones

The level of your thyroid  hormones may drop (hypothyroidism). You may feel tired or cold, gain weight, feel sad or depressed, or your voice may deepen.

Less often the level of thyroid hormones may increase. Or your thyroid might swell.

You will have regular blood tests to check your thyroid hormone levels.

Tummy (abdominal) pain

Contact your advice line if you have this. Depending on what is causing the pain, they might give you medicine to help. 

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.

Changes in the levels of minerals, electrolytes and proteins in your blood

Your blood contains different levels of minerals, electrolytes and proteins.

This treatment can change the levels of calcium, albumin, magnesium, sodium, potassium, creatinine, and bilirubin in your blood. It can also change liver and pancreas enzymes .

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 drop in the number of platelets in your blood - 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)
• your adrenal glands stop working properly - this may make you feel tired, sick or dizzy. If they stop working suddenly you can feel very ill
• a swollen pituitary gland – symptoms include headaches, changes in vision and tiredness
• diabetes – this is where your blood sugar levels are too high. Symptoms can include feeling very thirsty, being very tired, losing weight and feeling hungry
• low blood sugar levels
• loss of body fluid (dehydration)
• feeling confused
• numbness or tingling in your fingers or toes
• dizziness
• taste changes
• eye problems including changes in your sight, red or dry eyes
• problems with your heart muscle
• inflammation of a vein (phlebitis)
• a blocked nose
• inflammation of the bowel, stomach, liver or pancreas. Rarely you can get inflammation of the food pipe (oesophagus), kidneys or the bile ducts
• difficulty swallowing
• a sore or dry mouth
• hair loss or thinning
• muscle weakness or cramps
• your kidneys stop working properly
• a build up of fluid in the body – this is called oedema
• feeling like you have the flu
• a reaction to the treatment

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:

• your body stops making enough of some hormones
• swelling of the brain – this is called encephalitis. It can be life threatening. You should call an ambulance if you get a high temperature, headache, confusion or seizures
• conditions where the immune system attacks your own body such as Guillain Barré syndrome, Sjögren’s syndrome and lupus
• a nervous system condition that can affect your sight and hearing
• fluid around the heart
• asthma
• no sperm in the semen

Possible rare and long term side effects

This is a new drug in cancer treatment. So there is limited information available at the moment about possible rare and longer term effects that it may cause. Tell your doctor if you notice anything that is not normal for you.

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, food 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.

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.

Pregnancy and contraception

This treatment might harm a baby developing in the womb. It is important not to become pregnant or get someone pregnant while you're having treatment and for several months afterwards.

Talk to your doctor or nurse about effective contraception before starting treatment. Let them know straight away if you or your partner become pregnant while having treatment.

Breastfeeding

It is not known whether this drug comes 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, yellow fever and one of the shingles vaccines called Zostavax.

You can 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 it in relation to your cancer treatment

Members of your household who are aged 5 years or over are also able to have the COVID-19 vaccine. This is to help lower your risk of getting COVID-19 while having cancer treatment and until your immune system recovers from treatment.

Contact with others who have had immunisations - You can be in contact with other people who have had live vaccines as injections. Avoid close contact with people who have recently had live vaccines taken by mouth (oral vaccines) such as the oral typhoid vaccine. Sometimes people who have had the live shingles vaccine can get a shingles type rash. If this happens they should keep the area covered.

If your immune system is severely weakened, you should avoid contact with children who have had the flu vaccine as a nasal spray as this is a live vaccine. This is for 2 weeks following their vaccination.

Babies have the live rotavirus vaccine. The virus is in the baby’s poo for about 2 weeks and could make you ill if your immunity is low. Get someone else to change their nappies during this time if you can. If this isn't possible, wash your hands well after changing their nappy.

More information about this treatment

For further information about this treatment and possible side effects go to the electronic Medicines Compendium (eMC) website. You can find the patient information leaflet 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.