Axicabtagene ciloleucel
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]
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| Trade names | Yescarta |
| Other names | KTE-C19, Axi-cel |
| AHFS/Drugs.com | Professional Drug Facts |
| MedlinePlus | a618003 |
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| Routes of administration | Intravenous injection |
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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]
Side effects edit
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]
History edit
It was developed by California-based Kite Pharma.[12]
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.[13] 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.[14]
The FDA granted approval in October 2017, for the second-line treatment of diffuse large B-cell lymphoma.[9][15][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.[16] It is not indicated for the treatment of patients with primary central nervous system lymphoma.[16]
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.[16] Participants had not yet received treatment for relapsed or refractory lymphoma and were potential candidates for autologous hematopoietic stem cell transplantation (HSCT).[16] 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.[16] 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.[17]
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.[18][19]
References edit
- ^ a b "T Cells - Axicabtagene ciloleucel, cryopreserved - T - Yescarta (axicabtagene ciloleucel) Suspension for Intravenous Infusion". Therapeutic Goods Administration (TGA). Retrieved 16 September 2020.
- ^ "Updates to the Prescribing Medicines in Pregnancy database". Therapeutic Goods Administration (TGA). 12 May 2022. Retrieved 13 May 2022.
- ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 October 2023.
- ^ "Summary Basis of Decision (SBD) for Yescarta". Health Canada. 23 October 2014. Retrieved 29 May 2022.
- ^ "Yescarta- axicabtagene ciloleucel suspension". DailyMed. 31 January 2022. Retrieved 4 April 2022.
- ^ a b "Yescarta (axicabtagene ciloleucel)". U.S. Food and Drug Administration (FDA). 18 October 2017. Retrieved 1 April 2020.
- ^ "Yescarta EPAR". European Medicines Agency. 16 December 2014. Retrieved 27 February 2024.
- ^ Axicabtagene Ciloleucel (Yescarta) for B-Cell Lymphoma Med Lett Drugs Ther. 2018 Jul 16;60(1551):e122-123
- ^ a b c d e f "FDA approves CAR-T cell therapy to treat adults with certain types of large B-cell lymphoma". U.S. Food and Drug Administration (Press release). Retrieved 20 October 2017. This article incorporates text from this source, which is in the public domain.
- ^ Wang K, Wei G, Liu D (November 2012). "CD19: a biomarker for B cell development, lymphoma diagnosis and therapy". Experimental Hematology & Oncology. 1 (1): 36. doi:10.1186/2162-3619-1-36. PMC 3520838. PMID 23210908.
- ^ Halliley JL, Tipton CM, Liesveld J, Rosenberg AF, Darce J, Gregoretti IV, et al. (July 2015). "Long-Lived Plasma Cells Are Contained within the CD19(-)CD38(hi)CD138(+) Subset in Human Bone Marrow". Immunity. 43 (1): 132–45. doi:10.1016/j.immuni.2015.06.016. PMC 4680845. PMID 26187412.
- ^ "Kite's Yescarta (Axicabtagene Ciloleucel) Becomes First CAR T Therapy Approved by the FDA for the Treatment of Adult Patients With Relapsed or Refractory Large B-Cell Lymphoma After Two or More Lines of Systemic Therapy". Gilead (Press release). Retrieved 20 October 2017.
- ^ . Archived from the original on 21 June 2017. Retrieved 9 May 2017.
- ^ . Archived from the original on 25 April 2017. Retrieved 9 May 2017.
- ^ F.D.A. Approves Second Gene-Altering Treatment for Cancer 2017
- ^ a b c d e "FDA approves axicabtagene ciloleucel for second-line treatment of large B-cell lymphoma". U.S. Food and Drug Administration (FDA). 1 April 2022. Retrieved 4 April 2022. This article incorporates text from this source, which is in the public domain.
- ^ Westin J, Oluwole OO (July 2023). "Survival with Axicabtagene Ciloleucel in Large B-Cell Lymphoma". New England Journal of Medicine. 2023 (389): 148–157. doi:10.1056/NEJMoa2301665. PMID 37272527. S2CID 259074779.
- ^ Kansteiner F (26 January 2023). "After years of back-and-forth, Gilead's CAR-T Yescarta sways England's cost watchdog NICE". Fierce Pharma. Retrieved 31 January 2023.
- ^ biopharma-reporter.com (26 January 2023). "Gilead's Yescarta set to become England's first routinely available personalized immunotherapy for lymphoma". biopharma-reporter.com. Retrieved 31 January 2023.
External links edit
- "Axicabtagene Ciloleucel". National Cancer Institute. 20 October 2017.
- "Axicabtagene Ciloleucel". NCI Drug Dictionary. National Cancer Institute.