Axicabtagene ciloleucel

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Axicabtagene ciloleucel
Clinical data
Trade names Yescarta
Other namesKTE-C19, Axi-cel
AHFS/Drugs.com Professional Drug Facts
MedlinePlus a618003
License data
Pregnancy
category
Routes of
administration 		Intravenous injection
ATC code
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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]

Contents

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] 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. [15]

The FDA granted approval in October 2017, for the second-line treatment of diffuse large B-cell lymphoma. [9] [16] [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. [17] It is not indicated for the treatment of patients with primary central nervous system lymphoma. [17]

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. [17] Participants had not yet received treatment for relapsed or refractory lymphoma and were potential candidates for autologous hematopoietic stem cell transplantation (HSCT). [17] 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. [17] 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. [18]

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. [19] [20]

Society and culture

Names

Axicabtagene ciloleucel is the international nonproprietary name. [21]

Related Research Articles

In biology, chimeric antigen receptors (CARs)—also known as chimeric immunoreceptors, chimeric T cell receptors or artificial T cell receptors—are receptor proteins that have been engineered to give T cells the new ability to target a specific antigen. The receptors are chimeric in that they combine both antigen-binding and T cell activating functions into a single receptor.

<span class="mw-page-title-main">Diffuse large B-cell lymphoma</span> Type of blood cancer

Diffuse large B-cell lymphoma (DLBCL) is a cancer of B cells, a type of lymphocyte that is responsible for producing antibodies. It is the most common form of non-Hodgkin lymphoma among adults, with an annual incidence of 7–8 cases per 100,000 people per year in the US and UK. This cancer occurs primarily in older individuals, with a median age of diagnosis at ~70 years, although it can occur in young adults and, in rare cases, children. DLBCL can arise in virtually any part of the body and, depending on various factors, is often a very aggressive malignancy. The first sign of this illness is typically the observation of a rapidly growing mass or tissue infiltration that is sometimes associated with systemic B symptoms, e.g. fever, weight loss, and night sweats.

<span class="mw-page-title-main">Mantle cell lymphoma</span> Type of blood cancer

Mantle cell lymphoma (MCL) is a type of non-Hodgkin's lymphoma, comprising about 6% of cases. It is named for the mantle zone of the lymph nodes where it develops. The term 'mantle cell lymphoma' was first adopted by Raffeld and Jaffe in 1991.

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Arie S. Belldegrun, FACS, is an Israeli-American urologic oncologist, billionaire businessman and investor.

<span class="mw-page-title-main">Idelalisib</span> Chemical compound

Idelalisib, sold under the brand name Zydelig, is a medication used to treat certain blood cancers. Idelalisib acts as a phosphoinositide 3-kinase inhibitor; more specifically, it blocks P110δ, the delta isoform of the enzyme phosphoinositide 3-kinase. It was developed by Gilead Sciences. It is taken orally.

Kite Pharma is an American biotechnology company that develops cancer immunotherapy products, with a primary focus on genetically engineered autologous CAR T cell therapy, a cell-based therapy which relies on chimeric antigen receptors and T cells. Founded in 2009, and based in Santa Monica, California, it was acquired by Gilead Sciences in 2017.

Polatuzumab vedotin, sold under the brand name Polivy, is a CD79b-directed antibody-drug conjugate medication used for the treatment of diffuse large B-cell lymphoma (cancer). It was developed by the Genentech subsidiary of Roche.

<span class="mw-page-title-main">Juno Therapeutics</span> American biopharmaceutical company

Juno Therapeutics Inc was an American biopharmaceutical company founded in 2013 through a collaboration of the Fred Hutchinson Cancer Research Center, Memorial Sloan-Kettering Cancer Center and pediatrics partner Seattle Children's Research Institute. The company was launched with an initial investment of $120 million, with a remit to develop a pipeline of cancer immunotherapy drugs. The company raised $300 million through private funding and a further $265 million through their IPO.

Tisagenlecleucel, sold under the brand name Kymriah, is a CAR T cells medication for the treatment of B-cell acute lymphoblastic leukemia (ALL) which uses the body's own T cells to fight cancer.

<span class="mw-page-title-main">Umbralisib</span> Chemical compound

Umbralisib, sold under the brand name Ukoniq, is an anti-cancer medication for the treatment of marginal zone lymphoma (MZL) and follicular lymphoma (FL). It is taken by mouth.

<span class="mw-page-title-main">Loncastuximab tesirine</span> Medication

Loncastuximab tesirine, sold under the brand name Zynlonta, is a monoclonal antibody conjugate medication used to treat large B-cell lymphoma and high-grade B-cell lymphoma. It is an antibody-drug conjugate (ADC) composed of a humanized antibody targeting the protein CD19.

Lisocabtagene maraleucel, sold under the brand name Breyanzi, is a cell-based gene therapy used to treat B-cell lymphoma.

Brexucabtagene autoleucel, sold under the brand name Tecartus, is a cell-based gene therapy medication for the treatment of mantle cell lymphoma (MCL) and acute lymphoblastic leukemia (ALL).

Tafasitamab, sold under the brand name Monjuvi, is a medication used in combination with lenalidomide for the treatment of adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

Idecabtagene vicleucel, sold under the brand name Abecma, is a cell-based gene therapy to treat multiple myeloma.

Ciltacabtagene autoleucel, sold under the brand name Carvykti, is an anti-cancer medication used to treat multiple myeloma. Ciltacabtagene autoleucel is a BCMA -directed genetically modified autologous chimeric antigen receptor (CAR) T-cell therapy. Each dose is customized using the recipient's own T-cells, which are collected and genetically modified, and infused back into the recipient.

References

  1. 1 2 "T Cells - Axicabtagene ciloleucel, cryopreserved - T - Yescarta (axicabtagene ciloleucel) Suspension for Intravenous Infusion". Therapeutic Goods Administration (TGA). Archived from the original on 5 December 2023. Retrieved 16 September 2020.
  2. ↑ "Updates to the Prescribing Medicines in Pregnancy database". Therapeutic Goods Administration (TGA). 12 May 2022. Archived from the original on 3 April 2022. Retrieved 13 May 2022.
  3. ↑ "Summary Basis of Decision (SBD) for Yescarta". Health Canada . 23 October 2014. Archived from the original on 31 May 2022. Retrieved 29 May 2022.
  4. ↑ "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.
  5. ↑ "Yescarta- axicabtagene ciloleucel suspension". DailyMed. 31 January 2022. Archived from the original on 5 March 2022. Retrieved 4 April 2022.
  6. 1 2 "Yescarta (axicabtagene ciloleucel)". U.S. Food and Drug Administration (FDA). 18 October 2017. Archived from the original on 7 August 2020. Retrieved 1 April 2020.
  7. ↑ "Yescarta EPAR". European Medicines Agency. 16 December 2014. Archived from the original on 28 December 2023. Retrieved 27 February 2024.
  8. ↑ Axicabtagene Ciloleucel (Yescarta) for B-Cell Lymphoma Archived 29 November 2022 at the Wayback Machine Med Lett Drugs Ther. 2018 Jul 16;60(1551):e122-123
  9. 1 2 3 4 5 6 "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). Archived from the original on 5 March 2022. Retrieved 20 October 2017.PD-icon.svg 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. ↑ "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. Archived from the original on 19 April 2024. Retrieved 19 April 2024.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  13. ↑ "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). Archived from the original on 1 August 2019. Retrieved 20 October 2017.
  14. ↑ "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.
  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) March 2017". Archived from the original on 25 April 2017. Retrieved 9 May 2017.
  16. ↑ "F.D.A. Approves Second Gene-Altering Treatment for Cancer 2017". Archived from the original on 19 October 2017. Retrieved 19 October 2017.
  17. 1 2 3 4 5 "FDA approves axicabtagene ciloleucel for second-line treatment of large B-cell lymphoma". U.S. Food and Drug Administration (FDA). 1 April 2022. Archived from the original on 3 April 2022. Retrieved 4 April 2022.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  18. ↑ 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.
  19. ↑ Kansteiner F (26 January 2023). "After years of back-and-forth, Gilead's CAR-T Yescarta sways England's cost watchdog NICE". Fierce Pharma. Archived from the original on 31 January 2023. Retrieved 31 January 2023.
  20. ↑ biopharma-reporter.com (26 January 2023). "Gilead's Yescarta set to become England's first routinely available personalized immunotherapy for lymphoma". biopharma-reporter.com. Archived from the original on 28 January 2023. Retrieved 31 January 2023.
  21. ↑ World Health Organization (2018). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 79". WHO Drug Information. 32 (1). hdl: 10665/330941 .
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