0.4–2 × 10 8 cells Infusion fluid, dispersion
brexucabtagen-auto excel (CAR-positive, viable T cells )
What Descartes is and what it is used for
Descartes is a gene therapy medicine used to treat mantle cell lymphoma in adult patients. It is used when other medicines no longer work for you ( relapsed or refractory mantle cell lymphoma). The medicine has been specially developed for you and is made from your white blood cells, which have been modified and are then called brexukabtagen-auto excel.
Mantle cell lymphoma is a form of cancer that affects part of the body’s immune system. It affects a type of white blood cell called B lymphocytes. In mantle cell lymphoma, the B-lymphocytes multiply in an uncontrolled manner and accumulate in the lymph tissue, bone marrow, and the blood.
How Tecartus works
The white blood cells are taken out of your blood and genetically modified so that they target the cancer cells in question in your body. When Tecartus is introduced into your blood through an infusion, the white blood cells will kill the cancer cells.
What you need to know before you receive Tecartus
You should not receive Tecartus
- if you are allergic to any of the ingredients of this medicine (listed in section 6). If you think you may be allergic, consult your doctor.
- if you cannot receive the medicine needed to reduce the number of white blood cells in your blood (lymphocyte-reducing chemotherapy ) (see also section 3, “How Tecartus is given”).
Warnings and precautions
Descartes is made from your white blood cells and should only be given to you. This is called ” autologous use”.
Tests and checks
Before you are given Tecartus, your doctor will:
- check lungs, heart, kidneys, and blood pressure.
- check if you have any signs of infection or inflammation and decide if you need treatment for it before you receive Tecartus.
- check your cancer to see if it has worsened.
- look for signs of graft-versus-host disease, which can occur after a transplant. This happens when transplanted cells attack your body, causing symptoms such as rash, nausea, vomiting, diarrhea, and bloody stools.
- check your blood for uric acid and how many cancer cells are in your blood. This shows whether you are likely to develop a condition called tumor lysis syndrome. You may be given medication to help prevent this condition.
- check if you have hepatitis B, hepatitis C or HIV infection.
- check if you have received a vaccination in the previous 6 weeks or if you are scheduled to receive one in the coming months.
- check if you have previously received treatment with a medicine that attaches to the so-called CD19 protein.
In some cases, it may not be possible to carry out the planned treatment with Tecartus. If the Tecartus infusion is delayed for more than two weeks after you have received the lymphocyte-depleting chemotherapy, you may need to receive additional chemotherapy (see also section 3, “How Tecartus is given”).
After you have been treated with Tecartus:
Tell your doctor or nurse immediately or contact emergency medical services immediately if you have any of the following:
- Chills, extreme tiredness, weakness, dizziness, headache, cough, shortness of breath, fast or irregular pulse, severe nausea, vomiting, or diarrhea, may be symptoms of a condition known as cytokine release syndrome. Measure your temperature twice a day for 3-4 weeks after treatment with Tecartus. If your temperature is elevated, see your doctor immediately.
- Seizures, tremors or difficulty speaking or slurred speech, unconsciousness or reduced level of consciousness, confusion and disorientation, impaired balance or coordination.
- Fever, e.g. a temperature above 38 °C, may be a symptom of an infection.
- Extreme tiredness, weakness, and shortness of breath can be symptoms of a lack of red blood cells.
- Bleeding or bruising more easily, which can be symptoms of low levels of blood cells called platelets.
If any of the above applies to you, or if you are unsure, you should talk to a doctor or nurse.
Your doctor will regularly check your blood cell count as the number of blood cells and other blood components may decrease.
You will be asked if you want to enroll in a study register for at least 15 years. The study is conducted to gain increased knowledge of Tecartu’s long-term effects.
You must not donate blood, organs, tissues, or cells for transplantation.
Children and young people
Descartes should not be used by children and adolescents under the age of 18.
Other medicines and Tecartus
Tell the doctor or nurse if you are taking, have recently taken, or might take other medicines.
Before receiving Tecartus, tell your doctor or nurse if you are taking any medicines that weaken the immune system, such as cortisone, as these medicines may interfere with the effect of Tecartus.
In particular, you must not be given certain vaccines called live vaccines:
- in the 6 weeks before you are given a short course of lymphocyte-depleting chemotherapy to prepare your body for the Tecartus cells.
- during Tecartus treatment.
- after treatment while the immune system recovers.
Talk to your doctor if you need to be vaccinated.
Pregnancy, breastfeeding, and fertility
If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, consult your doctor before being given this medicine. This is because the effects of Tecartus in pregnant or breast-feeding women are unknown, and it may harm your unborn or breast-fed baby.
- If you are pregnant or think you may be pregnant after treatment with Tecartus, talk to your doctor immediately.
- You will be given a pregnancy test before the treatment starts. Descartes can only be given if the result shows that you are not pregnant.
Discuss pregnancy with your doctor if you have received Tecartus.
Driving ability and use of machinery
Descartes can cause problems such as altered or decreased level of consciousness, confusion, and seizures for 8 weeks after the medicine has been given.
You should not drive, use machinery or take part in activities that require you to be alert until at least 8 weeks have passed after treatment with Tecartus or your doctor says you have fully recovered.
Tecartus contains sodium, dimethyl sulfoxide (DMSO), and gentamicin
This medicine contains 300 mg of sodium (the main component of table salt) in each infusion. This corresponds to 15% of the recommended maximum daily intake of sodium for an adult. It also contains dimethyl sulfoxide and gentamicin, which can cause severe allergic reactions.
How Tecartus is given
Descartes is always given by healthcare professionals.
- Because Tecartus is made from your white blood cells, your blood cells will be collected from you to make your medicine. Your doctor will collect some of your blood via a catheter placed in a vein (a procedure called leukapheresis ). Some of your white blood cells are separated from your blood and the rest of the blood is returned to your vein. This may take 3 to 6 hours and may need to be repeated.
- Your white blood cells are sent to a Tecartus manufacturing center. It usually takes about 2 to 3 weeks to manufacture Tecartus but the time can vary.
Medicines are given before Tecartus treatment
A few days before you receive Tecartus, you will receive lymphocyte-depleting chemotherapy, which causes the modified white blood cells in Tecartus to multiply in your body while you receive the medicine.
During the 30 to 60 minutes before you are given Tecartus, you may be given other medicines. This is done to prevent infusion reactions and fever. These other medicines may include:
- paracetamol
- an antihistamine such as diphenhydramine.
How you are given Tecartus
Descartes is always given by a doctor in a qualified treatment unit.
- Descartes is given in a single dose.
- Your doctor or nurse will give you a single infusion of Tecartus through a catheter inserted into a vein (this is called an intravenous infusion ). Infusion one takes about 30 minutes.
After you get Tecartus
- You should remain close to the hospital where you were treated for at least 4 weeks after Tecartus treatment. Your doctor will recommend that you return to the hospital every day for at least 10 days or that you stay in the hospital as an inpatient for the first 10 days after Tecartus treatment. This is done so that the doctor can check whether your treatment is working and help you if you experience side effects.
If you miss an appointment, call the doctor or the treatment unit where you received your treatment as soon as possible to reschedule your appointment.
Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them. Do not try to treat your side effects yourself. Descartes can cause side effects that can be serious or life-threatening. Seek emergency care if you experience any of the following side effects after the Tecartus infusion.
Very common: may affect more than 1 in 10 users
- Fever, chills, and low blood pressure can cause symptoms such as dizziness, feeling faint, and fluid in the lungs which can be serious and can cause death (these are symptoms of a condition called cytokine release syndrome)
- Loss of consciousness or reduced level of consciousness, confusion or memory loss due to disturbances in the functioning of the brain, difficulty speaking or slurred speech, involuntary shaking ( tremor ), convulsive attacks (seizures), sudden confusion with agitation, disorientation, hallucinations or irritability ( delirium ).
- Fever, and chills, which may be signs of an infection
Other possible side effects are
Other side effects are listed below. If these side effects become serious, contact your doctor immediately.
Very common: may affect more than 1 in 10 users
- The abnormally low number of white blood cells can lead to an increased risk of infection.
- A low number of the blood cells that help to coagulate the blood ( thrombocytopenia ), changes the ability of the blood to clot. Symptoms may include extensive or prolonged bleeding or large, persistent bruising.
- High blood pressure
- Decreased number of red blood cells (the cells that transport oxygen). Symptoms can include extreme fatigue and loss of energy
- Extreme fatigue
- Fast or slow heartbeats
- Reduced amount of oxygen in the body’s tissue. Symptoms can include a change in skin tone, confusion, rapid breathing
- Shortness of breath, cough
- Nausea, constipation, diarrhea, abdominal pain, vomiting, difficulty swallowing
- Muscle pain, joint pain, bone pain, pain in arms and legs
- Lack of energy or strength, muscle weakness, difficulty moving, muscle spasms
- Headache
- Problems with the kidneys cause fluid to remain in the body and accumulate in the tissues ( edema ). This can lead to weight gain and difficulty breathing as well as decreased urine output.
- High levels of uric acid that show up in blood tests
- Low levels of sodium, phosphate, potassium, or calcium in blood tests
- Decreased appetite, pain in the mouth
- Difficulty sleeping, anxiety
- Swelling of the arms and legs, fluid around the lungs (alveolar effusion)
- Rash
- Low immunoglobulin levels. This is shown through a blood test and can lead to infection.
- The increased amount of liver enzymes in blood test
- Blood clots. Symptoms can include pain in the chest or back of the chest, breathing difficulties, coughing up blood, cramping pain, swelling in a leg, and warm and dark skin around the painful area.
- Nerve pain
Common: may affect up to 1 in 10 users
- Low levels of albumin in blood tests
- Abnormally heavy bleeding
- Irregular heartbeats ( arrhythmia ).
- Inability to control body movements
- Dry mouth, dehydration
- Shortness of breath ( respiratory insufficiency )
- Difficulty breathing which makes you unable to utter complete sentences; cough due to fluid in the lungs.
- Increased pressure inside the skull
How to store Tecartus
The following information is intended for medical use only.
Keep this medicine out of the sight and reach of children.
Use before the expiry date which is stated on the container label and the infusion bag after EXP.
Store froze in the gas phase of liquid nitrogen ≤ -150 °C until thawed for use.
Do not refreeze.
This medicine contains genetically modified human blood cells. Local guidelines for handling human biological waste must be followed for unused medicine or waste. As this medicine will be given by licensed healthcare professionals, they are responsible for the correct disposal of the product. These measures will help to protect the environment.
Contents of the packaging and other information
Contents declaration
The active substance is brexucabtagen-autoleucel. Each patient-specific single-use infusion bag contains a dispersion of anti-CD19-specific CAR T cells in approximately 68 mL for a target dose of 2 × 10 6 anti-CD19-specific CAR-positive viable T cells/kg.
Other ingredients (excipients) are Cryostor CS10, sodium chloride, and human albumin. See section 2 “Tecartus contains sodium”.
Appearance and package sizes of the medicine
Descartes is a clear to opaque, white to red dispersion for infusion, supplied in an infusion bag individually wrapped in a metal cassette. A single-use infusion bag contains approximately 68 ml of cell dispersion.
Kite Pharma EU BV
Tufstone 1
2132 NT Hoofddorp
Netherlands
Manufacturer
Kite Pharma EU BV
Tufstone 1
2132 NT Hoofddorp
Netherlands