High risk neuroblastoma differentiation therapy and immunotherapy

This leaflet is designed for parents whose children are being treated for neuroblastoma and who are about to start differentiation therapy and immunotherapy. It is intended to provide written information in addition to the explanation provided by the doctor.

Differentiation therapy

This is an oral treatment called isotretinoin (13-cis-retinoic acid) which is given over a period of six months. The aim of this treatment is to turn any remaining tumour cells, which have survived all of the other treatments, into non-aggressive mature cells

Immunotherapy

This is a type of intravenous antibody treatment called dinutuximab beta (previously known as antiGD2) which targets neuroblastoma cells by helping the immune system to recognise the cancer cells and attack them.

The treatment starts with two weeks of isotretinoin (13-cis-retinoic acid), which is either an oral capsule or oral suspension. The oral suspension should be used if administering via a nasogastric tube.

There are then five consecutive cycles of immunotherapy and differentiation therapy and each cycle lasts for five weeks. We will give you a plan with all the treatment dates on and discuss this with you.

The first week of each cycle is a 'rest week' with no treatment, and therefore you should be able to be at home. In the second and third weeks in each cycle the antibody will be given to your child through their central line (so-called Hickman line) continuously over ten consecutive days. Some or all of this time will be spent at CUH. The antibody infusion will end on day four of the third week of each cycle, and your child should be able to go home at that time.

The final two weeks of each cycle is a further 14 days of isotretinoin (13-cis-retinoic acid), which will commence on the day after completion of the dinutuximab beta infusion and finish on day 4 of week 5 of each cycle.

Care during the antibody treatment

The antibody is given slowly through a pump called a Baxter elastomeric infusor (pictured above).

The infusor needs to be kept at roughly the level of the Hickman line to infuse at the optimum rate. Therefore, when your child is in bed it should be kept next to the pillow, and when your child is up and about they can carry the infusor around in a small backpack. If you do not have a suitable bag, we may be able to provide you with an alternative. The balloon inside the infusor pump will slowly deflate as the medicine is administered.

Your child will be admitted to hospital for this part of the treatment. Prior to the antibody infusion, your child will be given medicine to help prevent allergic reactions.

Your child will also be given a painkiller drug called Gabapentin, which should be taken from the start of the first course of isotretinoin until the end of treatment. This drug is taken by mouth and is initially given once daily and built up to three times a day over two weeks. Your child can have additional painkillers if needed.

Depending upon how far away from the hospital you live and how your child reacts to the antibody during the first course; your child may be able to go home during subsequent courses of dinutuximab beta. If you live close enough to Cambridge, your child may be able to go home with the infusor and come back daily to the Paediatric Day Unit (PDU) for check-ups. If you do not live close to Cambridge your child may be discharged to Kingston House with the infusor and come back daily to PDU for check-ups. Your child will usually be admitted to the ward for the first few days of every course.

We will do blood tests prior to each course of isotretinoin to make sure it is safe to give the treatment. We also need to test your child’s urine prior to starting this treatment. These tests are usually done whilst your child is receiving the antibody treatment so this will not require an extra hospital visit. Blood tests are also required prior to each course of dinutuximab beta treatment and these can usually be done at your local hospital. An ECG (heart trace) will be done before the treatment is started.

Side effects of this treatment

Patients receiving immunotherapy treatment do experience some side effects. Some side effects may occur while your child is receiving the treatment. Other side effects may occur later and could be life threatening or even fatal. Drugs will be given to your child to make the side effects less serious and less uncomfortable. Patients will be monitored carefully and the treatment will be stopped if serious side effects develop.

Reproductive risks

It is unknown what effect this treatment may have on an unborn child. For this reason, if your child is of child bearing age, they will be asked to practise an effective method of birth control whilst they are having this treatment.

The use of isotretinoin (13-cis-retinoic acid) can cause serious birth defects to unborn children and therefore if you are pregnant, we recommend that you do not handle this medication for your child and you ask another family member to do this.

Here is a list of the more common side effects, as well as some rare more serious side effects. You can discuss these further with the doctor.

Side effects

Side effects of isotretinoin (13-cis-retinoic acid)

Likely side effects include:

• Dryness of the skin and mucous membranes (mouth, nose and eyes) – can occasionally cause bleeding.
• Dry, cracked and bleeding lips.
• An increased tendency to sunburn.
• Aches and pains in muscles and joints, including back pain.
• Elevation of fats in the blood and deranged liver function tests (monitored on blood tests).
• Increase in calcium in the blood which may require decreasing the dose.
• Altered blood counts, including anaemia, low white blood cells and either high or low platelets (blood components involved in clotting).

Rare side effects include:

• Severe allergic reaction.
• Headache, altered mood and/or behaviour.
• Bone weakness, which can lead to bone fractures or delayed healing of fractures.
• Inflammation in the gut causing diarrhoea and bleeding.

Side effects of dinutuximab beta

If your child develops a reaction whilst receiving dinutuximab beta, the infusion will be stopped immediately, and the reaction will be treated. Some of the side effects are more common in the first few courses and lessen in the later courses of dinutuximab beta.

Likely side effects include:

• Pain which may be in the back, abdomen (belly), joints, arms, legs and other parts of the body and will require administration of pain-relieving medications during the infusion.
• Numbness and tingling in the fingers and toes.
• A drop or rise in blood pressure.
• A fast heartbeat.
• Itching and hives.
• Fever.
• Nausea and/or vomiting.
• Low level of salt in the blood.
• Loss of appetite.
• Diarrhoea.

Rare side effects include:

• Severe allergic reactions which can be life-threatening.
• Irritation in the lungs that can cause coughing and wheezing.
• Seizures.
• A rapid heartbeat that could be life-threatening.
• Chest pain that may mean there is heart damage.
• Vascular leak syndrome: this is where fluid leaks out of tiny blood vessels and enters surrounding tissues. This can lead to dangerously low blood pressure or multiple organ failure.
• Severe rashes which can lead to life-threatening conditions.
• Swelling in the back of the eye.
• Damage to the optic nerve leading to potentially permanent decreased vision.
• Damage to the nerves controlling eye movements, resulting in blurred vision which is likely to be reversible but could be permanent.

Contact information

If you have any concerns or questions, please contact your clinical nurse specialist on 01223 216485.