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 InsertAxicabtagene 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
==References==
Category:Anti-CD19 CAR T-cells
Category:Anti-CD3 cellular therapy
Category:Anti-CD19 cellular therapy
Category:Anti-CD28 cellular therapy
Category:Intravenous medications
Category:Diffuse large B-cell lymphoma medications
Category:Follicular lymphoma medications
Category:High-grade B-cell lymphoma medications
Category:Indolent lymphoma medications
Category:Primary mediastinal B-cell lymphoma medications
Category:Transformed lymphoma medications
Category:EMA approved in 2018
Category:FDA approved in 2017
Category:Health Canada approved in 2019
Category:PMDA approved in 2021
Category:REMS program
Category:Kite Pharma product