Axicabtagene ciloleucel
Clinical data
Trade namesYescarta
Other namesKTE-C19, Axi-cel
AHFS/Drugs.comProfessional Drug Facts
MedlinePlusa618003
License data
Pregnancy
category
Routes of
administration		Intravenous injection
ATC code
Legal status
Legal status
Identifiers
DrugBank
UNII
KEGG

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]

Side 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]

History

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

  1. ^ a b "T Cells - Axicabtagene ciloleucel, cryopreserved - T - Yescarta (axicabtagene ciloleucel) Suspension for Intravenous Infusion". Therapeutic Goods Administration (TGA). Retrieved 16 September 2020.
  2. ^ "Updates to the Prescribing Medicines in Pregnancy database". Therapeutic Goods Administration (TGA). 12 May 2022. Retrieved 13 May 2022.
  3. ^ "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.
  4. ^ "Summary Basis of Decision (SBD) for Yescarta". Health Canada. 23 October 2014. Retrieved 29 May 2022.
  5. ^ "Yescarta- axicabtagene ciloleucel suspension". DailyMed. 31 January 2022. Retrieved 4 April 2022.
  6. ^ a b "Yescarta (axicabtagene ciloleucel)". U.S. Food and Drug Administration (FDA). 18 October 2017. Retrieved 1 April 2020.
  7. ^ "Yescarta EPAR". European Medicines Agency. 16 December 2014. Retrieved 27 February 2024.
  8. ^ Axicabtagene Ciloleucel (Yescarta) for B-Cell Lymphoma Med Lett Drugs Ther. 2018 Jul 16;60(1551):e122-123
  9. ^ 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. Public Domain This article incorporates text from this source, which is in the public domain.
  10. ^ 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.
  11. ^ 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.
  12. ^ "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.
  13. ^ "Kite to Present Two Plenary Presentations from the ZUMA-1 Pivotal Trial of Axicabtagene Ciloleucel at the 2017 American Association of Cancer Research Annual Meeting". Archived from the original on 21 June 2017. Retrieved 9 May 2017.
  14. ^ "Kite Completes Submission of U.S. Biologics License Application (BLA) for Axicabtagene Ciloleucel as the First CAR-T Therapy for the Treatment of Patients With Aggressive Non-Hodgkin Lymphoma (NHL) March 2017". Archived from the original on 25 April 2017. Retrieved 9 May 2017.
  15. ^ F.D.A. Approves Second Gene-Altering Treatment for Cancer 2017
  16. ^ 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. Public Domain This article incorporates text from this source, which is in the public domain.
  17. ^ 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.
  18. ^ 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.
  19. ^ 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.

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Intracellular chemotherapeutic agents / antineoplastic agents (L01)
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