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]
| Clinical data | |
|---|---|
| Trade names | Yescarta |
| Other names | KTE-C19, Axi-cel |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a618003 |
| License data | |
| Pregnancy category | |
| Routes of administration | Intravenous injection |
| ATC code | |
| Legal status | |
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| Identifiers | |
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| KEGG | |
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]
Society and culture
Names
Axicabtagene ciloleucel is the international nonproprietary name.[23]
References
External links
- "Axicabtagene Ciloleucel". National Cancer Institute. 20 October 2017.
- "Axicabtagene Ciloleucel". NCI Drug Dictionary. National Cancer Institute.
