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Axicabtagene ciloleucel
Clinical data
Trade names	Yescarta
Other names	KTE-C19, Axi-cel
AHFS/Drugs.com	Monograph
MedlinePlus	a618003
License data	US DailyMed: Axicabtagene_ciloleucel;
Pregnancy; category	AU: C; ;
Routes of; administration	Intravenous injection
ATC code	L01XL03 (WHO) ;
Legal status
Legal status	AU: Class 4 biological; CA: ℞-only / Schedule D; UK: POM (Prescription only); US: WARNINGRx-only; EU: Rx-only;
Identifiers
DrugBank	DB13915;
UNII	U2I8T43Y7R;
KEGG	D11144;

Axicabtagene ciloleucel, sold under the brand name Yescarta, is a medication used for the treatment for large B-cell lymphoma that has failed conventional treatment.^[8] T cells are removed from a person with lymphoma and genetically engineered to produce a specific T-cell receptor. The resulting chimeric antigen receptor T cells (CAR-Ts) that react to the cancer are then given back to the person to populate the bone marrow.^[9] Axicabtagene treatment carries a risk for cytokine release syndrome (CRS) and neurological toxicities.^[9]

Due to CD19 being a pan-B cell marker,^[10] the T-cells that are engineered to target CD19 receptors on the cancerous B cells^[9] also influence normal B cells, except some plasma cells.^[11]

Adverse effects

Because treatment with axicabtagene carries a risk of cytokine release syndrome and neurological toxicities, the FDA has mandated that hospitals be certified for its use prior to treatment of any patients.^[9]

In April 2024, the FDA label boxed warning was expanded to include T cell malignancies.^[12]

History

It was developed by California-based Kite Pharma.^[13]

Axicabtagene ciloleucel was awarded U.S. Food and Drug Administration (FDA) breakthrough therapy designation in October 2017, for diffuse large B-cell lymphoma, transformed follicular lymphoma, and primary mediastinal B-cell lymphoma.^[14]^[15] It also received priority review and orphan drug designation.^[9]

Based on the ZUMA-1 trial, Kite submitted a biologics license application for axicabtagene in March 2017, for the treatment of non-Hodgkin lymphoma.^[16]^[17]

The FDA granted approval in October 2017, for the second-line treatment of diffuse large B-cell lymphoma.^[9]^[18]^[6]

In April 2022, the FDA approved axicabtagene ciloleucel for adults with large B-cell lymphoma (LBCL) that is refractory to first-line chemoimmunotherapy or relapses within twelve months of first-line chemoimmunotherapy.^[19] It is not indicated for the treatment of patients with primary central nervous system lymphoma.^[19]

Approval was based on ZUMA-7, a randomized, open-label, multicenter trial in adults with primary refractory LBCL or relapse within twelve months following completion of first-line therapy.^[19] Participants had not yet received treatment for relapsed or refractory lymphoma and were potential candidates for autologous hematopoietic stem cell transplantation (HSCT).^[19] A total of 359 participants were randomized 1:1 to receive a single infusion of axicabtagene ciloleucel following fludarabine and cyclophosphamide lymphodepleting chemotherapy or to receive second-line standard therapy, consisting of two or three cycles of chemoimmunotherapy followed by high-dose therapy and autologous HSCT in participants who attained complete remission or partial remission.^[19] In the ZUMA-7 trial, patients treated with axicabtagene ciloleucel had superior clinical outcomes compared with the previous standard of care, including improved overall survival with an estimated 4-year overall survival rate of 54.6% for axicabtagene ciloleucel, compared with 46% for the previous standard of care.^[20]

In January 2023, the National Institute for Health and Care Excellence (NICE) recommended axicabtagene ciloleucel to treat adult patients with diffuse large B-cell lymphoma (DLBCL) or primary mediastinal large B-cell lymphoma (PMBCL) who have already been treated with two or more systemic therapies.^[21]^[22]