Tisagenlecleucel

What it is and how it works

Mechanism of Action KYMRIAH is a CD19-directed genetically modified autologous T cell immunotherapy which involves reprogramming a patient’s own T cells with a transgene encoding a chimeric antigen receptor (CAR) to identify and eliminate CD19-expressing malignant and normal cells. The CAR is comprised of a murine single-chain antibody fragment which recognizes CD19 and is fused to intracellular signaling domains from 4-1BB (CD137) and CD3 zeta. The CD3 zeta component is critical for initiating T cell activation and antitumor activity, while 4-1BB enhances the expansion and persistence of KYMRIAH.

Mechanism class: CD19 Receptor Interactions

Indications

is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of: Patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse. Adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, high grade B-cell lymphoma and DLBCL arising from follicular lymphoma. Limitations of Use : KYMRIAH is not indicated for treatment of patients with primary central nervous system lymphoma. Adult patients with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy. This indication is approved under accelerated approval based on response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

Dosage and administration (summary)

For autologous use only. For intravenous use only. Administer a lymphodepleting regimen if needed before infusion of KYMRIAH. Do NOT use a leukodepleting filter. Verify the patient’s identity prior to infusion. Premedicate with acetaminophen and an H1-antihistamine. Confirm availability of tocilizumab prior to infusion. ( 2.2 , 5.1 ) Dosing of KYMRIAH is based on the number of chimeric antigen receptor (CAR)-positive viable T cells. Pediatric and Young Adult B-cell ALL (up to 25 years of age) • For patients 50 kg or less, administer 0.2 to 5.0 x 10 6 CAR-positive viable T cells per kg body weight intravenously.

Contraindications

None. None.

Warnings and precautions

Hypersensitivity Reactions: Monitor for hypersensitivity reactions during infusion. Serious Infections: Monitor patients for signs and symptoms of infection; treat appropriately. Prolonged Cytopenias: Patients may exhibit ≥ Grade 3 cytopenias for several weeks following KYMRIAH infusion. Prolonged neutropenia has been associated with increased risk of infection. Hypogammaglobulinemia: Monitor and provide replacement therapy until resolution. Assess immunoglobulin levels in newborns of mothers treated with KYMRIAH.

Pregnancy

Pregnancy Risk Summary There are no available data with KYMRIAH use in pregnant women. No animal reproductive and developmental toxicity studies have been conducted with KYMRIAH to assess whether it can cause fetal harm when administered to a pregnant woman. It is not known if KYMRIAH has the potential to be transferred to the fetus.

Storage and supply

is supplied as a frozen suspension of genetically modified autologous T cells in an infusion bag(s) labeled for the specific recipient. KYMRIAH is shipped directly to the cell lab associated with the infusion center in a liquid nitrogen Dewar. Product and patient-specific labels are located inside the Dewar.

Source: Tisagenlecleucel (Kymriah) — US FDA prescribing information, 2025-12-16, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.