Axicabtagene ciloleucel explained

Tradename:Yescarta
Dailymedid:Axicabtagene_ciloleucel
Pregnancy Au:C
Pregnancy Au Comment:[1] [2]
Routes Of Administration:Intravenous injection
Atc Prefix:L01
Atc Suffix:XL03
Legal Au Comment:Class 4 biological
Legal Ca:Rx-only
Legal Ca Comment:/ Schedule D[3]
Legal Uk:POM
Legal Us:Rx-only
Legal Us Comment:[4]
Legal Eu:Rx-only
Legal Eu Comment:[5]
Drugbank:DB13915
Unii:U2I8T43Y7R
Kegg:D11144
Synonyms:KTE-C19, Axi-cel

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.[6] 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.[7] Axicabtagene treatment carries a risk for cytokine release syndrome (CRS) and neurological toxicities.[7]

Due to CD19 being a pan-B cell marker,[8] the T-cells that are engineered to target CD19 receptors on the cancerous B cells[7] also influence normal B cells, except some plasma cells.[9]

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.[7]

In April 2024, the FDA label boxed warning was expanded to include T cell malignancies.[10]

History

It was developed by California-based Kite Pharma.[11]

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.[12] [13] It also received priority review and orphan drug designation.[7]

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] [15]

The FDA granted approval in October 2017, for the second-line treatment of diffuse large B-cell lymphoma.[7] [16] [17]

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.[18] It is not indicated for the treatment of patients with primary central nervous system lymphoma.

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. Participants had not yet received treatment for relapsed or refractory lymphoma and were potential candidates for autologous hematopoietic stem cell transplantation (HSCT). 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. 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.[19]

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.[20] [21]

Society and culture

Names

Axicabtagene ciloleucel is the international nonproprietary name.[22]

External links

Notes and References

  1. Web site: T Cells - Axicabtagene ciloleucel, cryopreserved - T - Yescarta (axicabtagene ciloleucel) Suspension for Intravenous Infusion . Therapeutic Goods Administration (TGA) . 16 September 2020 . 5 December 2023 . https://web.archive.org/web/20231205044852/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2020-PI-01410-1 . live .
  2. Web site: Updates to the Prescribing Medicines in Pregnancy database . Therapeutic Goods Administration (TGA) . 12 May 2022 . 13 May 2022 . 3 April 2022 . https://web.archive.org/web/20220403064059/https://www.tga.gov.au/updates-prescribing-medicines-pregnancy-database . live .
  3. Web site: Summary Basis of Decision (SBD) for Yescarta . . 23 October 2014 . 29 May 2022 . 31 May 2022 . https://web.archive.org/web/20220531060614/https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00442&lang=en . live .
  4. Web site: Yescarta- axicabtagene ciloleucel suspension . DailyMed . 31 January 2022 . 4 April 2022 . 5 March 2022 . https://web.archive.org/web/20220305191831/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9b70606e-b99c-4272-a0f1-b5523cce0c59 . live .
  5. Web site: European Medicines Agency . Yescarta EPAR . 16 December 2014 . 27 February 2024 . 28 December 2023 . https://web.archive.org/web/20231228155139/https://www.ema.europa.eu/en/medicines/human/EPAR/yescarta . live .
  6. https://secure.medicalletter.org/TML-article-1551f Axicabtagene Ciloleucel (Yescarta) for B-Cell Lymphoma
  7. FDA approves CAR-T cell therapy to treat adults with certain types of large B-cell lymphoma. U.S. Food and Drug Administration. 20 October 2017. 5 March 2022. https://web.archive.org/web/20220305153215/https://www.fda.gov/news-events/press-announcements/fda-approves-car-t-cell-therapy-treat-adults-certain-types-large-b-cell-lymphoma. live.
  8. Wang K, Wei G, Liu D . CD19: a biomarker for B cell development, lymphoma diagnosis and therapy . Experimental Hematology & Oncology . 1 . 1 . 36 . November 2012 . 23210908 . 10.1186/2162-3619-1-36 . 3520838 . free .
  9. Halliley JL, Tipton CM, Liesveld J, Rosenberg AF, Darce J, Gregoretti IV, Popova L, Kaminiski D, Fucile CF, Albizua I, Kyu S, Chiang KY, Bradley KT, Burack R, Slifka M, Hammarlund E, Wu H, Zhao L, Walsh EE, Falsey AR, Randall TD, Cheung WC, Sanz I, Lee FE . Long-Lived Plasma Cells Are Contained within the CD19(-)CD38(hi)CD138(+) Subset in Human Bone Marrow . Immunity . 43 . 1 . 132–45 . July 2015 . 26187412 . 10.1016/j.immuni.2015.06.016 . 4680845 . free .
  10. Web site: FDA Requires Boxed Warning for T cell Malignancies Following Treatment with BCMA-Directed or CD19-Directed Autologous Chimeric Antigen Receptor (CAR) T cell Immunotherapies . U.S. Food and Drug Administration (FDA) . 18 April 2024 . 19 April 2024 . 19 April 2024 . https://web.archive.org/web/20240419003946/https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/fda-requires-boxed-warning-t-cell-malignancies-following-treatment-bcma-directed-or-cd19-directed . live .
  11. 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. 20 October 2017. 1 August 2019. https://web.archive.org/web/20190801085434/https://www.gilead.com/news-and-press/press-room/press-releases/2017/10/kites-yescarta-axicabtagene-ciloleucel-becomes-first-car-t-therapy-approved-by-the-fda-for-the-treatment-of-adult-patients-with-relapsed-or-refrac. live.
  12. 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 . 9 May 2017 . Kite Pharma . 30 March 2017 . https://web.archive.org/web/20170621015853/http://ir.kitepharma.com/releasedetail.cfm?ReleaseID=1019378 . 21 June 2017 . dead.
  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 . Kite Pharma . Business Wire . 30 March 2017 . 1 July 2024 . 1 July 2024 . https://web.archive.org/web/20240701065759/https://www.businesswire.com/news/home/20170330005439/en/ . live .
  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) . Kite Pharma . 31 March 2017 . 9 May 2017 . https://web.archive.org/web/20170425154310/http://ir.kitepharma.com/releasedetail.cfm?ReleaseID=1019623 . 25 April 2017 . dead .
  15. 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) . Kite Pharma . Business Wire . 31 March 2017 . 1 July 2024 . https://web.archive.org/web/20221206181145/http://www.businesswire.com/news/home/20170331005751/en/ . 2022-12-06 .
  16. News: F.D.A. Approves Second Gene-Altering Treatment for Cancer . . 18 October 2017 . 19 October 2017 . 19 October 2017 . https://web.archive.org/web/20171019150155/https://www.nytimes.com/2017/10/18/health/immunotherapy-cancer-kite.html . live .
  17. Web site: Yescarta (axicabtagene ciloleucel) . U.S. Food and Drug Administration (FDA) . 18 October 2017 . 1 April 2020 . 7 August 2020 . https://web.archive.org/web/20200807204158/https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/yescarta-axicabtagene-ciloleucel . live .
  18. Web site: FDA approves axicabtagene ciloleucel for second-line treatment of large B-cell lymphoma . U.S. Food and Drug Administration (FDA) . 1 April 2022 . 4 April 2022 . 3 April 2022 . https://web.archive.org/web/20220403223447/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-axicabtagene-ciloleucel-second-line-treatment-large-b-cell-lymphoma . live .
  19. Westin J, Oluwole OO . Survival with Axicabtagene Ciloleucel in Large B-Cell Lymphoma . New England Journal of Medicine . 2023 . 389 . 148–157 . July 2023 . 37272527 . 10.1056/NEJMoa2301665 . 259074779 . 11585/961908 . free .
  20. Web site: Kansteiner . Fraiser . 26 January 2023 . After years of back-and-forth, Gilead's CAR-T Yescarta sways England's cost watchdog NICE . 31 January 2023 . Fierce Pharma . 31 January 2023 . https://web.archive.org/web/20230131122034/https://www.fiercepharma.com/pharma/after-years-back-and-forth-gilead-and-kites-car-t-yescarta-woos-uk-cost-watchdog-nice . live .
  21. Web site: biopharma-reporter.com . Gilead's Yescarta set to become England's first routinely available personalized immunotherapy for lymphoma . 31 January 2023 . biopharma-reporter.com . 26 January 2023 . 28 January 2023 . https://web.archive.org/web/20230128053425/https://www.biopharma-reporter.com/Article/2023/01/26/gilead-s-yescarta-set-to-become-england-s-first-routinely-available-personalized-immunotherapy-for-lymphoma . live .
  22. ((World Health Organization)) . 2018 . International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 79 . WHO Drug Information . 32 . 1 . 10665/330941 . free . World Health Organization .

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