Kymriah Injection: Uses, Dosage, Side Effects, Precautions and Alternates

Quick overview

Kymriah Injection (tisagenlecleucel) is a CD19-directed CAR T-cell immunotherapy made from a patient's own T-cells. It is used to treat certain types of B-cell acute lymphoblastic leukemia and specific B-cell lymphomas that have not responded to, or have returned after, other treatments. Kymriah is given as a single one-time intravenous infusion rather than an ongoing therapy. Because it can cause serious reactions such as cytokine release syndrome and nervous system problems, it is given at specialized treatment centers with close monitoring.

What is Kymriah Injection

Kymriah is made from your own white blood cells called T-cells. T-cells are important for your immune system to work properly. Your T-cells are removed from your blood, sent to a lab where they are genetically modified to recognize and attack cancer cells, and then given back to you as a one-time infusion.

Kymriah Injection uses

• B-cell acute lymphoblastic leukemia (ALL) in children and young adults up to and including 25 years of age who are refractory, have relapsed after stem cell transplant, are ineligible for stem cell transplant, or have had a second or later relapse
• Diffuse large B-cell lymphoma (DLBCL) in adults whose disease has returned or did not respond after two or more prior treatments
• Follicular lymphoma (FL), grade 1, 2, or 3a, in adults after two or more prior lines of treatment

Benefits of Kymriah Injection

• Can produce complete or partial remission in patients whose blood cancer has not responded to, or has come back after, other treatments
• Single, one-time infusion rather than ongoing repeated dosing
• High rates of overall response seen in clinical trials for ALL, DLBCL, and follicular lymphoma

How Kymriah Injection works

Your own T-cells are taken from your blood and modified in a lab to carry a receptor that lets them recognize a marker called CD19 found on certain cancer cells. When these modified cells are infused back into your blood, they find and destroy the cancer cells.

Kymriah Injection dosage

Your blood cells are collected through a process called leukapheresis, which can take 3 to 6 hours and may need to be repeated. It takes about 3 to 4 weeks to manufacture Kymriah from your cells, though timing may vary. While waiting for Kymriah to be made, you may receive other therapy to help control your cancer.

Before the infusion, you will usually receive a short course of chemotherapy to prepare your body. You will be given other medicines such as acetaminophen and an antihistamine about 30 to 60 minutes before the infusion to reduce the risk of reactions.

Kymriah is given as an intravenous infusion, which usually takes less than one hour. Kymriah is a one-time treatment, not an ongoing therapy. After infusion, plan to stay within about 2 hours' travel of the treatment center for at least 4 weeks so your care team can monitor you. Your doctor will have you return to the hospital 2 to 3 times during at least the first week after infusion to check for side effects.

Available forms and strengths

• Cell suspension for intravenous infusion, supplied in one or more patient-specific infusion bags

Side effects of Kymriah Injection

Common

• Abdominal pain, constipation, weight loss
• Muscle weakness, muscle spasms
• Swelling of the arms or legs
• Swelling of the belly
• Changes or loss of vision
• Sore throat, stuffy nose, flu-like symptoms
• Bloating, mouth sores, dry mouth
• Skin reactions such as rash, hot flushes, night sweats, itching, skin reddening, excessive sweating
• Muscle cramps
• Anxiety
• Sleep disturbances
• Headache
• Fever
• Fatigue
• Nausea, vomiting, diarrhea

Serious

• Cytokine release syndrome (CRS) - high fever, chills, fast heartbeat, difficulty breathing, nausea, vomiting, diarrhea, muscle or joint pain, low blood pressure, dizziness
• Neurological toxicities (including ICANS) - altered or decreased consciousness, confusion, delirium, agitation, seizures, difficulty speaking and understanding speech, loss of balance
• Serious infections, including life-threatening or fatal infections
• Prolonged low blood cell counts (cytopenias) - risk of infection, bleeding, bruising, fatigue
• Hypogammaglobulinemia (low antibody levels) leading to increased risk of infection
• Hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS)
• Secondary cancers, including T-cell malignancies
• Serious hypersensitivity reactions, including anaphylaxis
• Tumour lysis syndrome
• Capillary leak syndrome
• Heart problems, including heart failure or cardiac arrest
• Kidney injury
• Bleeding or clotting problems

Warnings and precautions

• Kymriah can cause cytokine release syndrome (CRS), a common and potentially life-threatening reaction. You will be closely watched for this after your infusion.
• Serious or life-threatening nervous system problems, including a condition called ICANS, can occur, sometimes at the same time as CRS.
• New blood cancers, including cancers of T-cells, have occurred after treatment with Kymriah and similar therapies, sometimes within weeks of infusion, and can be fatal. You should be monitored for this for the rest of your life.
• Kymriah should only be given at a specialized treatment center by healthcare professionals trained in its use, because of the risk of serious complications.
• Do not receive live vaccines for at least 6 weeks before starting the chemotherapy that prepares your body for Kymriah, during treatment, or until your immune system has recovered afterward.
• After receiving Kymriah, do not donate blood, organs, tissues, sperm, eggs, or other cells.
• Some commercial HIV tests may give a false positive result after you receive Kymriah because of genetic similarities between the viral vector used to make Kymriah and HIV.
• Women who can become pregnant should use effective birth control after treatment, and men should use a condom during sex, because the effects of Kymriah on a baby are not known.
• Kymriah is not recommended during pregnancy because its effects on an unborn baby are not known, and the modified cells may cross the placenta and cause harm. Your doctor will check if you are pregnant before treatment and will discuss any pregnancy plans with you.
• It isn't known whether Kymriah passes into breast milk, so a risk to a breastfed baby cannot be ruled out. Discuss breastfeeding with your doctor after treatment.
• People with poor kidney function were not included in clinical studies and may be more vulnerable to side effects, requiring extra monitoring.
• People with poor liver function were not included in clinical studies and may be more vulnerable to side effects, requiring extra monitoring.
• Alcohol should be discussed with the oncology team during treatment and recovery.
• Do not drive or operate machinery for at least 8 weeks after your infusion, since Kymriah can cause altered or decreased consciousness, confusion, or seizures during this time.

Storage

• Kymriah must be stored in a temperature-monitored system at or below -120°C
• The expiry date is indicated on the product label
• Do not thaw the product until it is ready to be used
• Any unused product or waste material should be disposed of according to local requirements and local biosafety guidelines for genetically modified organisms
• All material that has been in contact with Kymriah should be handled and disposed of as potentially infectious waste according to local hospital procedures

When to see a doctor

• Get emergency help right away if you have a fever, chills or shaking, difficulty breathing, confusion, severe nausea/vomiting/diarrhea, severe muscle or joint pain, very low blood pressure, or dizziness/lightheadedness — these can be signs of cytokine release syndrome.
• Seek urgent medical attention if you or someone caring for you notices confusion, agitation, delirium, altered or decreased consciousness, seizures, difficulty speaking or understanding speech, or loss of balance — these may be signs of serious nervous system problems (ICANS).
• Tell your healthcare provider right away if you develop a fever, chills, or any other signs of infection.
• Tell your healthcare provider right away if you feel tired, weak, or short of breath, or notice unusual bruising or bleeding, since Kymriah can lower your blood cell counts.
• Seek emergency treatment right away if you have signs of a serious allergic reaction, such as difficulty breathing, very low blood pressure, dizziness, swelling under the skin, rash, nausea, or vomiting.
• If you develop a new cancer after treatment, contact your doctor so it can be reported and evaluated.

Alternatives

• Yescarta
• Breyanzi
• Tecartus