Axicabtagene ciloleucel

{{Short description|Medication to treat large B-cell lymphoma}} {{Use dmy dates|date=September 2024}} {{cs1 config |name-list-style=vanc |display-authors=6}} {{Infobox drug | image = | width = | alt = | caption =

| pronounce = | tradename = Yescarta | Drugs.com = {{Drugs.com|monograph|axicabtagene}} | MedlinePlus = a618003 | DailyMedID = Axicabtagene_ciloleucel | pregnancy_AU = C | pregnancy_AU_comment = <ref name="AU Yescarta PI">{{cite web | title=T Cells - Axicabtagene ciloleucel, cryopreserved - T - Yescarta (axicabtagene ciloleucel) Suspension for Intravenous Infusion | website=Therapeutic Goods Administration (TGA) | url=http://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2020-PI-01410-1 | access-date=16 September 2020 | archive-date=5 December 2023 | archive-url=https://web.archive.org/web/20231205044852/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2020-PI-01410-1 | url-status=live }}</ref><ref>{{cite web | title=Updates to the Prescribing Medicines in Pregnancy database | website=Therapeutic Goods Administration (TGA) | date=12 May 2022 | url=https://www.tga.gov.au/resources/resource/guidance/updates-prescribing-medicines-pregnancy-database | access-date=13 May 2022 | archive-date=3 April 2022 | archive-url=https://web.archive.org/web/20220403064059/https://www.tga.gov.au/updates-prescribing-medicines-pregnancy-database | url-status=live }}</ref> | pregnancy_category= | routes_of_administration = Intravenous injection | class = | ATC_prefix = L01 | ATC_suffix = XL03 | ATC_supplemental =

| legal_AU = | legal_AU_comment = Class 4 biological<ref name="AU Yescarta PI" /> | legal_BR =  | legal_BR_comment = | legal_CA = Rx-only | legal_CA_comment = / Schedule D<ref>{{cite web | title=Summary Basis of Decision (SBD) for Yescarta | website=Health Canada | date=23 October 2014 | url=https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00442&lang=en | access-date=29 May 2022 | archive-date=31 May 2022 | archive-url=https://web.archive.org/web/20220531060614/https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00442&lang=en | url-status=live }}</ref> | legal_DE =  | legal_DE_comment = | legal_NZ =  | legal_NZ_comment = | legal_UK = POM | legal_UK_comment = | legal_US = Rx-only | legal_US_comment = <ref name="Yescarta FDA label">{{cite web | title=Yescarta- axicabtagene ciloleucel suspension | website=DailyMed | date=31 January 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9b70606e-b99c-4272-a0f1-b5523cce0c59 | access-date=4 April 2022 | archive-date=5 March 2022 | archive-url=https://web.archive.org/web/20220305191831/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9b70606e-b99c-4272-a0f1-b5523cce0c59 | url-status=live }}</ref><ref name="FDA Yescarta" /> | legal_EU = Rx-only | legal_EU_comment = <ref name="Yescarta EPAR">{{cite web | website=European Medicines Agency | title=Yescarta EPAR | date=16 December 2014 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/yescarta | access-date=27 February 2024 | archive-date=28 December 2023 | archive-url=https://web.archive.org/web/20231228155139/https://www.ema.europa.eu/en/medicines/human/EPAR/yescarta | url-status=live }}</ref> | legal_UN =  | legal_UN_comment = | legal_status =

| IUPAC_name = | chemical_formula = | C= | H= | Ag= | Al= | As= | Au= | B= | Bi= | Br= | Ca= | Cl= | Co= | F= | Fe= | Gd= | I= | K= | Li= | Mg= | Mn= | N= | Na= | O= | P= | Pt= | S= | Sb= | Se= | Sr= | Tc= | Zn= | charge= | molecular_weight = | SMILES = | StdInChI = | StdInChI_comment = | StdInChIKey = | density = | density_notes = | melting_point = | melting_high = | melting_notes = | boiling_point = | boiling_notes = | solubility = | sol_units = | specific_rotation = }}

'''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.<ref>[https://secure.medicalletter.org/TML-article-1551f Axicabtagene Ciloleucel (Yescarta) for B-Cell Lymphoma] {{Webarchive|url=https://web.archive.org/web/20221129054852/https://secure.medicalletter.org/TML-article-1551f |date=29 November 2022 }} Med Lett Drugs Ther. 2018 Jul 16;60(1551):e122-123</ref> 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.<ref name=FDAapprove>{{cite press release|title=FDA approves CAR-T cell therapy to treat adults with certain types of large B-cell lymphoma|url=https://www.fda.gov/news-events/press-announcements/fda-approves-car-t-cell-therapy-treat-adults-certain-types-large-b-cell-lymphoma|website=U.S. Food and Drug Administration|access-date=20 October 2017|archive-date=5 March 2022|archive-url=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}} {{PD-notice}}</ref> Axicabtagene treatment carries a risk for cytokine release syndrome (CRS) and neurological toxicities.<ref name=FDAapprove/>

Due to CD19 being a pan-B cell marker,<ref>{{cite journal | vauthors = Wang K, Wei G, Liu D | title = CD19: a biomarker for B cell development, lymphoma diagnosis and therapy | journal = Experimental Hematology & Oncology | volume = 1 | issue = 1 | page = 36 | date = November 2012 | pmid = 23210908 | doi = 10.1186/2162-3619-1-36 | pmc = 3520838 | doi-access = free }}</ref> the T-cells that are engineered to target CD19 receptors on the cancerous B cells<ref name=FDAapprove/> also influence normal B cells, except some plasma cells.<ref>{{cite journal | vauthors = 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 | title = Long-Lived Plasma Cells Are Contained within the CD19(-)CD38(hi)CD138(+) Subset in Human Bone Marrow | journal = Immunity | volume = 43 | issue = 1 | pages = 132–45 | date = July 2015 | pmid = 26187412 | doi = 10.1016/j.immuni.2015.06.016 | pmc = 4680845 | doi-access = free }}</ref>

==Adverse effects== Because treatment with axicabtagene carries a risk of cytokine release syndrome and neurological toxicities, the Food and Drug Administration (FDA) has mandated that hospitals be certified for its use prior to treatment of any patients.<ref name=FDAapprove/>

In April 2024, the FDA label boxed warning was expanded to include T cell malignancies.<ref>{{cite web | title=FDA Requires Boxed Warning for T cell Malignancies Following Treatment with BCMA-Directed or CD19-Directed Autologous Chimeric Antigen Receptor (CAR) T cell Immunotherapies | website=U.S. Food and Drug Administration (FDA) | date=18 April 2024 | url=https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/fda-requires-boxed-warning-t-cell-malignancies-following-treatment-bcma-directed-or-cd19-directed | access-date=19 April 2024 | archive-date=19 April 2024 | archive-url=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 }} {{PD-notice}}</ref>

==History== It was developed by California-based Kite Pharma.<ref>{{cite press release|title=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|url=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|website=Gilead|access-date=20 October 2017|archive-date=1 August 2019|archive-url=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|url-status=live}}</ref>

Axicabtagene ciloleucel was awarded U.S. FDA breakthrough therapy designation in October 2017, for diffuse large B-cell lymphoma, transformed follicular lymphoma, and primary mediastinal B-cell lymphoma.<ref>{{cite press release | url=http://ir.kitepharma.com/releasedetail.cfm?ReleaseID=1019378 | title=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 | access-date=9 May 2017 | website=Kite Pharma | date=30 March 2017 | archive-url=https://web.archive.org/web/20170621015853/http://ir.kitepharma.com/releasedetail.cfm?ReleaseID=1019378 | archive-date=21 June 2017 }}</ref><ref>{{cite press release | title=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 | publisher=Kite Pharma | via=Business Wire | date=30 March 2017 | url=https://www.businesswire.com/news/home/20170330005439/en/ | access-date=1 July 2024 | archive-date=1 July 2024 | archive-url=https://web.archive.org/web/20240701065759/https://www.businesswire.com/news/home/20170330005439/en/ | url-status=live }}</ref> It also received priority review and orphan drug designation.<ref name=FDAapprove/>

Based on the ZUMA-1 trial, Kite submitted a biologics license application for axicabtagene in March 2017, for the treatment of non-Hodgkin lymphoma.<ref>{{cite press release | url=http://ir.kitepharma.com/releasedetail.cfm?ReleaseID=1019623 | title=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) | website=Kite Pharma | date=31 March 2017 | access-date=9 May 2017 | archive-url=https://web.archive.org/web/20170425154310/http://ir.kitepharma.com/releasedetail.cfm?ReleaseID=1019623 | archive-date=25 April 2017 }}</ref><ref>{{cite press release | title=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) | publisher=Kite Pharma | via=Business Wire | date=31 March 2017 | url=https://www.businesswire.com/news/home/20170331005751/en/ | access-date=1 July 2024 | archive-url=https://web.archive.org/web/20221206181145/http://www.businesswire.com/news/home/20170331005751/en/ | archive-date=6 December 2022 }}</ref>

The FDA granted approval in October 2017, for the second-line treatment of diffuse large B-cell lymphoma.<ref name=FDAapprove/><ref>{{cite news |url=https://www.nytimes.com/2017/10/18/health/immunotherapy-cancer-kite.html |title=F.D.A. Approves Second Gene-Altering Treatment for Cancer |website=The New York Times | date=18 October 2017 |access-date=19 October 2017 |archive-date=19 October 2017 |archive-url=https://web.archive.org/web/20171019150155/https://www.nytimes.com/2017/10/18/health/immunotherapy-cancer-kite.html |url-status=live }}</ref><ref name="FDA Yescarta">{{cite web | title=Yescarta (axicabtagene ciloleucel) | website=U.S. Food and Drug Administration (FDA) | date=18 October 2017 | url=https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/yescarta-axicabtagene-ciloleucel | access-date=1 April 2020 | archive-date=7 August 2020 | archive-url=https://web.archive.org/web/20200807204158/https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/yescarta-axicabtagene-ciloleucel }}</ref>

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.<ref name="FDA 20220401">{{cite web | title=FDA approves axicabtagene ciloleucel for second-line treatment of large B-cell lymphoma | website=U.S. Food and Drug Administration (FDA) | date=1 April 2022 | url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-axicabtagene-ciloleucel-second-line-treatment-large-b-cell-lymphoma | access-date=4 April 2022 | archive-date=3 April 2022 | archive-url=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 }} {{PD-notice}}</ref> It is not indicated for the treatment of patients with primary central nervous system lymphoma.<ref name="FDA 20220401" />

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.<ref name="FDA 20220401" /> Participants had not yet received treatment for relapsed or refractory lymphoma and were potential candidates for autologous hematopoietic stem cell transplantation (HSCT).<ref name="FDA 20220401" /> 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.<ref name="FDA 20220401" /> 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.<ref name="pmid37272527">{{cite journal | vauthors = Westin J, Oluwole OO | title = Survival with Axicabtagene Ciloleucel in Large B-Cell Lymphoma | journal = New England Journal of Medicine | volume = 2023 | issue = 389 | pages = 148–157 | date = July 2023 | pmid = 37272527 | doi = 10.1056/NEJMoa2301665 | s2cid = 259074779 | hdl = 11585/961908 | hdl-access = free }}</ref>

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.<ref>{{cite web |last=Kansteiner |first=Fraiser |date=26 January 2023 |title=After years of back-and-forth, Gilead's CAR-T Yescarta sways England's cost watchdog NICE |url=https://www.fiercepharma.com/pharma/after-years-back-and-forth-gilead-and-kites-car-t-yescarta-woos-uk-cost-watchdog-nice |access-date=31 January 2023 |website=Fierce Pharma |archive-date=31 January 2023 |archive-url=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 |url-status=live }}</ref><ref>{{cite web |last=biopharma-reporter.com |title=Gilead's Yescarta set to become England's first routinely available personalized immunotherapy for lymphoma |url=https://www.biopharma-reporter.com/Article/2023/01/26/gilead-s-yescarta-set-to-become-england-s-first-routinely-available-personalized-immunotherapy-for-lymphoma |access-date=31 January 2023 |website=biopharma-reporter.com |date=26 January 2023 |archive-date=28 January 2023 |archive-url=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 |url-status=live }}</ref>

== Society and culture == === Names === Axicabtagene ciloleucel is the international nonproprietary name.<ref>{{cite journal | year = 2018 | title = International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 79 | journal = WHO Drug Information | volume = 32 | issue = 1 | hdl = 10665/330941 | hdl-access = free }}</ref>

== References == {{reflist}}

== External links == * {{cite web | title=Axicabtagene Ciloleucel | date=20 October 2017 | publisher=National Cancer Institute | url=https://www.cancer.gov/about-cancer/treatment/drugs/axicabtageneciloleucel }} * {{cite web | title=Axicabtagene Ciloleucel | website=NCI Drug Dictionary | publisher=National Cancer Institute | url=https://www.cancer.gov/publications/dictionaries/cancer-drug/def/axicabtagene-ciloleucel }}

{{DEFAULTSORT:Axicabtagene Ciloleucel}} Category:Cancer treatments Category:Approved gene therapies Category:CAR T-cell therapy Category:Gilead Sciences Category:Orphan drugs Category:Antineoplastic drugs