Rituximab and Idelalisib (R-Idelalisib)

R-Idelalisib is a cancer drug combination for treatment for chronic lymphocytic leukaemia (CLL). It includes rituximab and idelalisib.

You might have this treatment if:

• your CLL has come back (relapsed) after it has been treated
• it’s your first treatment and your CLL has specific gene changes (faults or mutations) known as 17p deletion or TP53 mutation

How does R-Idelalisib work?

Idelalisib works by blocking a protein called PI3K inside cancer cells which tell the cancer to grow. Some lymphomas and leukaemia cells have too much PI3K. So by blocking this protein, idelalisib may shrink the cancer or stop it growing for some time. Idelalisib is also called a PI3K inhibitor.

Rituximab is a monoclonal antibody. It targets a protein called CD20 on the surface of the leukaemia and lymphoma cells. Rituximab sticks to all the CD20 proteins it finds. Then the cells of the immune system pick out the marked cells and kill them.

How do you have idelalisib?

You have rituximab as a drip into the bloodstream (intravenously). You take idelalisib as a tablet twice a day. You can take it with or without food and swallow it whole with a glass of water.

Taking your tablets or capsules

You should take the right dose, not more or less.

Talk to your healthcare team before you stop taking a cancer drug, or if you miss a dose.

Having rituximab 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.

How often do you have R-Idelalisib?

You have R-Idelalisib as cycles of treatment. This means you have the drugs and then a rest to allow your body to recover.

Each cycle lasts for 28 days (4 weeks). You usually have a total of 8 doses of rituximab, which takes up to 6 cycles of treatment. But you continue idelalisib for as long as it is working and the side effects aren’t bad.

You usually have cycle 1 in the following way:

You usually have cycle 2 in the following way:

You usually have cycle 3 to cycle 6 in the following way:

You then continue to take idelalisib tablets twice a day for as long as its working and the side effects aren’t too bad.

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 R-Idelalisib?

How often and how severe the side effects are can vary from person to person. They also depend on what other treatments you're having.

When to contact your team

Your doctor, nurse or pharmacist will go through the possible side effects. They will monitor you 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. 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:

Risk of infection

Increased risk of getting an infection

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

Your doctor may give you antibiotics to prevent infections. You might carry on taking antibiotics for a few months after stopping idelalisib.

Loose or watery poo (diarrhoea)

Contact your advice line if you have

diarrhoea

Your doctor may give you anti diarrhoea medicine to take home with you after treatment. Eat less fibre, avoid raw fruits, fruit juice, cereals and vegetables, and drink plenty to replace the fluid lost.

Idelalisib can cause diarrhoea to start up to several months after you start treatment. This can also cause inflammation of the bowel (colitis).

Bruising, bleeding gums or nosebleeds

This is due to a

drop in the number of platelets in your blood

Allergic reaction

An allergic reaction that can cause a rash, shortness of breath, redness or swelling of the face and throat  and dizziness - some allergic reactions can be life threatening, alert your nurse or doctor if notice any of these symptoms.

You might also have a high temperature (fever) and chills. This sometimes happens during the first infusion.

Skin changes

Skin problems

Rarely you may develop a severe skin reaction. This may start as tender red patches on the skin which then leads to peeling or blistering of the skin. These symptoms can be caused by one of two conditions called Toxic Epidermal Necrolysis (TEN) or Stevens Johnson Syndrome (SJS).

These rare conditions can be life threatening. Contact your team straight away.

Liver changes

You might have liver changes that are usually mild and unlikely to cause symptoms. They usually go back to normal when treatment finishes. Less commonly you might have liver damage.

You have regular blood tests to check for any changes in the way your liver is working.

High levels of cholesterol

Cholesterol is a fatty substance which helps cells in the body to work normally. When the cholesterol level is too high it could have an effect on your heart. You usually have blood tests to check your cholesterol levels.

Feeling or being sick

Feeling or being sick

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.

Hair loss

You could

lose all your hair

Headaches

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

Tiredness and weakness (fatigue)

You might feel

very tired

Various things can help you to reduce tiredness and cope with it, for example exercise. Some research has shown that taking gentle exercise can give you more energy. It is important to balance exercise with resting.

Low levels of an antibody called immunoglobulin G in your body

Immunoglobulin G is an antibody made by the immune system to fight bacteria and viruses. You have regular blood tests during and after treatment to check for 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:

• lung changes such as inflammation of the lungs (pneumonitis), cough, chest pain and shortness of breath. Rarely you might have narrowing and swelling of the airways (asthma)
• breathlessness and looking pale – caused by low levels of red blood cells (anaemia)
• high blood sugar levels – you might to check them more often if you are diabetic
• weight loss
• fluid build up in different parts of the body such as the face causing swelling
• changes to levels of substances in the blood such as a low calcium and high enzyme liver called LDH - you will have regular blood tests to check this
• difficulty sleeping (insomnia)
• feeling restless or anxious
• feeling dizzy or lightheaded
• watery eyes or inflammation of the outer covering of the eyeball (conjunctivitis)
• ringing in the ears (tinnitus)
• heart problems such as changes to heart rhythm, changes to how the heart muscle is working, or a heart attack. Rarely you might get chest pain.
• runny nose
• difficulty opening your bowels (constipation)
• tummy (abdominal) pain
• indigestion symptoms include heartburn, bloating and burping
• difficulty swallowing
• loss of appetite
• sore mouth and throat
• sweating more than usual, especially at night
• pain in different parts of the body such as back, neck, muscle or joint pain. You might have pain where your cancer is. Rarely you might get pain at the site of the infusion
• feeling generally unwell (malaise)
• being sick (vomiting)
• a reduced sense of touch or tingling or pricking in your hands and feet
• getting stiff and difficulty moving due to the brain telling the muscles in your body to tighten (hypertonia)

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:

• high levels of chemicals in your blood due to the breakdown of tumour cells (tumour lysis syndrome) - you have regular blood tests to check for this
• cytokines are group of proteins in the body that play an important part in boosting the immune system. Rituximab stimulates the immune system to make large amounts of cytokines. This can cause symptoms which can be severe. Some of the symptoms include fever, chills, a headache, difficulty breathing, and dizziness. Let your medical team know straight away if you have any of these symptoms. You can have treatment to reverse the syndrome.
• taste changes
• feeling low (depression) or nervous
• sight loss
• enlarged tummy (abdomen)
• changes to the way your blood clots
• your bone marrow not making enough essential blood cells (aplastic anaemia)
• a blood disorder where your red blood cells get destroyed faster than they can be made (haemolytic anaemia)
• swelling of the lymph nodes or glands

Coping with side effects

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

What else do I need to know?

Other medicines, foods and drinks

Drugs can interact with some other medicines and herbal products. Tell your doctor about any medicines you are taking. This includes vitamins, herbal supplements and over the counter remedies.

Many medicines, foods and herbal supplements can react with idelalisib. In particular medicines, foods and herbal supplements which contain CYP enzymes.

Contraception and pregnancy

This treatment might harm a baby developing in the womb. It is important not to become pregnant or father a child while you're having treatment and for 12 months afterwards.

It is unknown if idelalisib interferes with hormonal contraceptives such as the pill. So it is advised that women should add the barrier method such as a condom as a second form of contraception during this treatment and for 12 months after.

Talk to your doctor or nurse about effective contraception before starting treatment.

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 and for 12 months afterwards.

Treatment for other conditions

Always tell other doctors, nurses, pharmacists or dentists that you’re having this treatment. For example, if you need treatment for anything else, including teeth problems.

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.