Kymriah (Tisagenlecleucel): What It Is and What to Expect

This is not a drug in the usual sense. It is made from your own cells, once, for you alone.

T cells are collected from your blood. In a laboratory a new gene is added to them, so they build a receptor on their surface called a chimeric antigen receptor, or CAR. That receptor recognizes CD19, a marker carried by B cells, including cancerous ones.

The changed cells are grown in number, frozen, and shipped back. When they are put into you, they hunt B cells and multiply inside your body while they do it.

Kymriah is the brand name; tisagenlecleucel is the generic name.

Three groups, and the wording is precise.

B-cell acute lymphoblastic leukemia, in patients up to 25 years of age, where the disease is refractory or in a second or later relapse.

Large B-cell lymphoma in adults, after two or more earlier lines of treatment. That covers diffuse large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL that arose from follicular lymphoma. The label states clearly that it is not for primary lymphoma of the central nervous system.

Follicular lymphoma in adults, after two or more earlier lines of treatment. This one holds an accelerated approval, based on how many people responded and for how long, with confirmatory trials still required.

The collection is called leukapheresis. Blood leaves through one line, a machine separates out the white cells, and the rest returns through another. It takes a few hours and you are awake throughout.

Manufacturing then takes several weeks. During that wait you may need other chemotherapy to keep the disease in check, and that carries its own risks.

Shortly before the infusion you have a short course of chemotherapy, usually fludarabine and cyclophosphamide. This is called lymphodepletion. It makes room for the new cells to expand.

The infusion itself is short. It is one bag, or sometimes two or three, given through a drip.

This does not get said often enough, and it is in the label's own counselling section.

Manufacturing has failed in up to 9% of attempts. If that happens, a second attempt can be made. It is worth asking your team in advance what the plan would be, so the answer is not being worked out in the moment.

The boxed warning names three risks. Two of them arrive early.

Cytokine release syndrome happens when the new cells activate and immune signals surge. It brings high fever, chills, breathlessness, severe nausea, vomiting or diarrhea, bad muscle and joint pain, dizziness and very low blood pressure. It can be life-threatening. It is treated, often with a drug called tocilizumab, which the hospital has ready before your infusion.

Nervous system effects can come with it or separately: confusion, agitation, trouble speaking or understanding, loss of balance, drowsiness, and seizures. Families often notice these before the patient does, so a relative or friend should know the list too.

Neither is something to wait out. Fever after CAR T-cell therapy is an emergency until proven otherwise.

The third risk is later. T cell cancers have occurred after treatment with CD19-directed CAR T-cell therapies, including this one.

The label gives two instructions. Stay within reach of a healthcare facility for at least 2 weeks after the infusion. And do not drive for at least 2 weeks, because of the nervous system effects.

You are also monitored daily during the first week. Your center may ask for longer than the label minimum, and it will want an adult with you.

Blood counts can stay low for weeks. Antibody levels often fall, sometimes needing replacement, and infection risk stays higher for a long time. Tell any clinician you see, and mention it before any vaccine.

You will be screened for hepatitis B, hepatitis C and HIV before your cells are collected.

Afterwards the label asks for lifelong monitoring for secondary cancers, and for any that occur to be reported to the manufacturer. That is not a sign anyone expects trouble. It is how a treatment this new keeps being checked.

Keep the wallet card or contact details you are given. Anyone treating you in an emergency needs to know you have had CAR T-cell therapy.

• Call the CAR T-cell team at once, at any hour, if your temperature reads 100.4°F (38°C) or higher at any point after your cells go in, or you get hard shaking chills. The CDC treats a fever this high during cancer treatment as a medical emergency, and after CAR T-cell therapy it needs assessing within the hour, not the day. If you cannot reach the team fast, go to an emergency department, show the wallet card and say you have had CAR T-cell therapy. Call 911 or go to an emergency department if fever comes with confusion, a seizure, slurred or muddled speech, severe breathlessness, or blood pressure low enough that you cannot stay upright.
• Call your care team the same day if sickness or diarrhea will not stop, or you feel steadily worse without a measured temperature. Family should call too if you seem agitated, drowsy, off balance, or simply not yourself.
• Call your care team within a day or two if you keep picking up infections, bruise or bleed easily, or feel steadily more short of breath in the weeks after treatment. Counts and antibody levels stay low for a long time.

• https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aad3ba54-dfd3-4cb3-9e2b-c5ef89559189
• https://www.cancer.gov/about-cancer/treatment/drugs/tisagenlecleucel
• https://www.cdc.gov/cancer-preventing-infections/patients/fever.html