Tisagenlecleucel (Kymriah)

Mechanism of action

From the NCI Drug Dictionary: Autologous T lymphocytes transduced with a modified lentiviral vector expressing a chimeric antigen receptor (CAR) consisting of an anti-CD19 scFv (single chain variable fragment) and the zeta chain of the TCR/CD3 complex (CD3-zeta), coupled to the signaling domain of 4-1BB (CD137), with potential immunomodulating and antineoplastic activities. Upon transfusion, tisagenlecleucel direct the T lymphocytes to CD19-expressing tumor cells, thereby inducing a selective toxicity in CD19-expressing tumor cells.

Toxicity management

• Link to REMS program

Diseases for which it is established

• B-cell acute lymphoblastic leukemia
• Diffuse large B-cell lymphoma
• High-grade B-cell lymphoma
• Transformed lymphoma

Diseases for which it is used

• Follicular lymphoma

Diseases for which it was used

• Chronic lymphocytic leukemia
• Multiple myeloma

History of changes in FDA indication

• 2017-08-30: Granted FDA regular approval for the treatment of patients up to age 25 years with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse. (Based on ELIANA)
• 2018-05-01: FDA approval expanded for adult patients with relapsed or refractory 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. (Based on JULIET)
• 2022-05-27: Granted accelerated approval for adult patients with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy. (Based on ELARA)

History of changes in EMA indication

• 2017-08-30: Initial marketing authorisation

History of changes in Health Canada indication

• 2018-09-05: Initial notice of compliance
• 2022-12-19: Notice of compliance with conditions for adult patients with relapsed or refractory 1, 2, 3a follicular lymphoma (FL) after two or more lines of systemic therapy.

Also known as

• Code name: CART19, CTL019
• Generic name: tisagenlecleucel-T
• Brand name: Kymriah