Axicabtagene ciloleucel (Yescarta)

Mechanism of action

From the NCI Drug Dictionary: A preparation of autologous peripheral blood T-lymphocytes (PBTL) that have been transduced with a gammaretroviral vector expressing a chimeric antigen receptor (CAR) consisting of an anti-CD19 single chain variable fragment (scFv) coupled to the costimulatory signaling domain CD28 and the zeta chain of the T-cell receptor (TCR)/CD3 complex (CD3 zeta), with potential immunostimulating and antineoplastic activities. Upon intravenous infusion and re-introduction of axicabtagene ciloleucel into the patient, these cells bind to and induce selective toxicity in CD19-expressing tumor cells.

Toxicity management

• Link to REMS

Diseases for which it is established (work in progress)

• Diffuse large B-cell lymphoma
• High-grade B-cell lymphoma
• Primary mediastinal B-cell lymphoma
• Transformed lymphoma

Diseases for which it is used

• Follicular lymphoma

Patient Drug Information

• Axicabtagene ciloleucel (Yescarta) Package Insert

History of changes in FDA indication

• 2017-10-18: Granted initial approval for the treatment of 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, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma. NOT indicated for the treatment of patients with primary central nervous system lymphoma. (Based on ZUMA-1)
• 2021-03-05: Granted accelerated approval for adult patients with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy. (Based on ZUMA-5)
• 2022-04-01: Approved for adult patients with large B-cell lymphoma (LBCL) that is refractory to first-line chemoimmunotherapy or relapses within 12 months of first-line chemoimmunotherapy. It is not indicated for the treatment of patients with primary central nervous system lymphoma. (Based on ZUMA-7)

History of changes in EMA indication

• 2018-08-23: Initial marketing authorization as Yescarta. Yescarta is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and primary mediastinal large B-cell lymphoma (PMBCL), after two or more lines of systemic therapy. (Based on ZUMA-1)
• 2022-06-21: Extension of indication to include the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) after three or more lines of systemic therapy.
• 2022-10-14: Extension of indication to include treatment of adult patients with relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL).

History of changes in Health Canada indication

• 2019-02-13: Initial notice of compliance
• 2022-09-29: Notice of compliance with conditions for the treatment of adult patients with relapsed or refractory grade 1, 2 or 3a follicular lymphoma (FL) after two or more lines of systemic therapy.

History of changes in PMDA indication

• 2021-01-22: Initial approval

Also known as

• Code name: KTE-C19
• Generic names: Axicel, Axi-cel
• Brand name: Yescarta