How it is administered

Tisagenlecleucel is administered as a single-dose intravenous infusion. It is an autologous cell therapy, meaning it is made from your own T cells, which are collected from your blood, genetically modified in a laboratory, and then returned to you as an infusion. The infusion is given in a hospital or specialized treatment center, and the dose is based on your weight and the specific type of blood cancer being treated.

Before receiving tisagenlecleucel, you may receive a short course of chemotherapy (called lymphodepleting chemotherapy) to prepare your body for the treatment. The actual infusion usually takes less than an hour, but you will be closely monitored for several weeks afterward for side effects.

How it works

Tisagenlecleucel is a type of CAR-T cell therapy, which stands for Chimeric Antigen Receptor T-cell therapy. It works by reprogramming your own immune cells (T cells) to recognize and attack cancer cells.

First, T cells are collected from your blood. In the lab, these cells are genetically modified to produce special receptors (CARs) on their surface. These CARs are designed to recognize a protein called CD19, which is found on the surface of many B-cell cancers, including certain leukemias and lymphomas. Once the modified T cells are infused back into your body, they can find and destroy cancer cells that have the CD19 protein.

This therapy can lead to a rapid and powerful immune response against cancer, but it can also cause significant side effects, so patients are monitored very closely after treatment.

Who Should take it

Tisagenlecleucel is indicated for patients with certain types of blood cancers who have not responded to other treatments:

• Children and young adults (up to 25 years old) with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory (not responding to treatment) or in second or later relapse.
• Adults with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.
• Adults with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy.

This therapy is generally considered when other standard treatments have not worked, and it is given in specialized centers with experience in CAR-T cell therapy.

Who should not take it

There are no absolute contraindications listed for tisagenlecleucel, but it is not recommended for certain patients:

• Patients with active, uncontrolled infections should not receive tisagenlecleucel until the infection is resolved.
• Patients with unresolved serious adverse reactions from previous chemotherapy (such as pulmonary or cardiac toxicity, or hypotension), active graft-versus-host disease, or worsening leukemia burden after lymphodepleting chemotherapy should have treatment delayed until these issues are managed.
• Patients with primary central nervous system lymphoma should not be treated with tisagenlecleucel.

Women who are pregnant or planning to become pregnant should discuss the risks with their doctor, as the effects on pregnancy are unknown and there is a potential risk to the fetus.

Commonly used with

Tisagenlecleucel is often used after other treatments for blood cancers have failed. Before the infusion, patients usually receive lymphodepleting chemotherapy (such as fludarabine and cyclophosphamide, or sometimes bendamustine) to prepare the body for the CAR-T cells.

During and after treatment, supportive medications may be used to manage side effects, such as tocilizumab and corticosteroids for cytokine release syndrome.

Commonly tested with

Tisagenlecleucel has been tested in combination with lymphodepleting chemotherapy regimens (fludarabine and cyclophosphamide, or bendamustine) as part of the treatment protocol.

For management of side effects, it is often tested and used alongside medications like tocilizumab (for cytokine release syndrome) and corticosteroids (for severe immune reactions). These supportive therapies are an important part of the overall treatment plan for patients receiving tisagenlecleucel.