Brexucabtagene autoleucel

Brexucabtagene autoleucel
Clinical data
Trade namesTecartus
Other namesKTE-X19, brexu-cel
AHFS/Drugs.comTecartus
License data
Pregnancy
category
Routes of
administration		Intravenous
ATC code
Legal status
Legal status
Identifiers
DrugBank
UNII
KEGG

Brexucabtagene autoleucel, sold under the brand name Tecartus, is a cell-based gene therapy medication for the treatment of mantle cell lymphoma (MCL)[10][11][7] and acute lymphoblastic leukemia (ALL).[12]

The most common side effects include serious infections, low blood cell counts and a weakened immune system.[10] The most common side effects for the treatment of ALL include fever, CRS, hypotension, encephalopathy, tachycardias, nausea, chills, headache, fatigue, febrile neutropenia, diarrhea, musculoskeletal pain, hypoxia, rash, edema, tremor, infection with pathogen unspecified, constipation, decreased appetite, and vomiting.[12]

Brexucabtagene autoleucel is a chimeric antigen receptor T cell therapy and is the first cell-based gene therapy approved by the U.S. Food and Drug Administration (FDA) for the treatment of mantle cell lymphoma.[10]

Brexucabtagene autoleucel was approved for medical use in the United States in July 2020,[10][7][13] and in the European Union in December 2020.[8]

Medical uses

Brexucabtagene autoleucel is indicated for the treatment of adults with relapsed or refractory mantle cell lymphoma.[10] It is also indicated for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia.[12]

Mantle cell lymphoma (MCL) is a rare form of cancerous B-cell non-Hodgkin's lymphoma that usually occurs in middle-aged or older adults.[10] In people with MCL, B-cells, a type of white blood cell which help the body fight infection, change into cancer cells that start to form tumors in the lymph nodes and quickly spread to other areas of the body.[10]

Each dose of brexucabtagene autoleucel is a customized treatment created using the recipient's own immune system to help fight the lymphoma.[10] The recipient's T cells, a type of white blood cell, are collected and genetically modified to include a new gene that facilitates the targeting and killing of the lymphoma cells.[10] These modified T cells are then infused back into the recipient.[10]

Adverse effects

The FDA label carries a boxed warning for cytokine release syndrome (CRS), which is a systemic response to the activation and proliferation of CAR-T cells causing high fever and flu-like symptoms, and for neurologic toxicities.[6][10][12] Both cytokine release syndrome and neurologic toxicities can be fatal or life-threatening.[10]

In April 2024, the FDA label boxed warning was expanded to include T cell malignancies.[14]

The most common side effects of brexucabtagene autoleucel include serious infections, low blood cell counts and a weakened immune system.[10] Side effects from treatment usually appear within the first one to two weeks after treatment, but some side effects may occur later.[10] The most common Grade 3 or higher reactions were anemia, neutropenia, thrombocytopenia, hypotension, hypophosphatemia, encephalopathy, leukopenia, hypoxia, pyrexia, hyponatremia, hypertension, infection – pathogen unspecified, pneumonia, hypocalcemia, and lymphopenia.[11]

Because of the risk of cytokine release syndrome and neurological toxicities, brexucabtagene autoleucel was approved with a risk evaluation and mitigation strategy (REMS), which includes elements to assure safe use.[10][11] The risk mitigation measures for brexucabtagene autoleucel are identical to those of the REMS Program for another CAR-T therapy, axicabtagene ciloleucel (Yescarta).[10]

History

Brexucabtagene autoleucel was approved for medical use in the United States in July 2020.[7][13]

Approval was based on ZUMA-2 (NCT02601313), an open-label, multicenter, single-arm trial of 74 participants with relapsed or refractory MCL who had previously received anthracycline- or bendamustine-containing chemotherapy, an anti-CD20 antibody, and a Bruton tyrosine kinase inhibitor.[11][10] Participants received a single infusion of brexucabtagene autoleucel following completion of lymphodepleting chemotherapy.[11] The primary efficacy outcome measure was objective response rate (ORR) per Lugano [2014] criteria as assessed by an independent review committee.[11] The complete remission rate after treatment with brexucabtagene autoleucel was 62 percent, with an objective response rate of 87 percent.[10]

The application for brexucabtagene autoleucel was approved under the accelerated approval pathway and it was granted priority review, breakthrough therapy, and orphan drug designations.[10][11]

Efficacy for adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia was evaluated in ZUMA-3 (NCT02614066), a single-arm multicenter trial that evaluated brexucabtagene autoleucel, a CD19-directed chimeric antigen receptor (CAR) T-cell therapy.[12] Participants received a single infusion of brexucabtagene autoleucel following completion of lymphodepleting chemotherapy.[12]

Society and culture

Names

Brexucabtagene autoleucel is the international nonproprietary name.[15]

References

  1. ^ "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.
  2. ^ "Tecartus (brexucabtagene autoleucel) Pregnancy & Lactation". Medscape Drugs & Diseases. 27 July 2020. Archived from the original on 1 August 2020. Retrieved 1 August 2020.
  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. ^ "TECARTUS (Gilead Sciences Pty LTD) | Therapeutic Goods Administration (TGA)". Archived from the original on 2 January 2024. Retrieved 2 January 2024.
  5. ^ "Summary Basis of Decision (SBD) for Tecartus". Health Canada. 23 October 2014. Archived from the original on 29 May 2022. Retrieved 29 May 2022.
  6. ^ a b "Tecartus- brexucabtagene autoleucel suspension". DailyMed. 31 July 2020. Archived from the original on 20 March 2023. Retrieved 24 August 2020.
  7. ^ a b c d "Tecartus". U.S. Food and Drug Administration (FDA). 24 July 2020. STN: BL 125703. Archived from the original on 25 July 2020. Retrieved 24 July 2020.
  8. ^ a b "Tecartus EPAR". European Medicines Agency (EMA). 13 October 2020. Archived from the original on 18 November 2023. Retrieved 25 January 2021.
  9. ^ "Tecartus Product information". Union Register of medicinal products. Archived from the original on 5 March 2023. Retrieved 3 March 2023.
  10. ^ a b c d e f g h i j k l m n o p q r s "FDA Approves First Cell-Based Gene Therapy For Adult Patients with Relapsed or Refractory MCL". U.S. Food and Drug Administration (FDA). 24 July 2020. Archived from the original on 25 July 2020. Retrieved 24 July 2020. Public Domain This article incorporates text from this source, which is in the public domain.
  11. ^ a b c d e f g "FDA approves brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma". U.S. Food and Drug Administration (FDA). 24 July 2020. Archived from the original on 3 August 2020. Retrieved 1 August 2020. Public Domain This article incorporates text from this source, which is in the public domain.
  12. ^ a b c d e f "FDA approves brexucabtagene autoleucel for relapsed or refractory B-cell precursor acute lymphoblastic leukemia". U.S. Food and Drug Administration (FDA). 1 October 2021. Archived from the original on 2 October 2021. Retrieved 2 October 2021. Public Domain This article incorporates text from this source, which is in the public domain.
  13. ^ a b "U.S. FDA Approves Kite's Tecartus, the First and Only CAR T Treatment for Relapsed or Refractory Mantle Cell Lymphoma" (Press release). Kite Pharma. 24 July 2020. Archived from the original on 25 July 2020. Retrieved 24 July 2020 – via Business Wire.
  14. ^ "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. Public Domain This article incorporates text from this source, which is in the public domain.
  15. ^ World Health Organization (2022). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 87". WHO Drug Information. 36 (1). hdl:10665/352794.

Further reading

  • Clinical trial number NCT02601313 for "A Phase 2 Multicenter Study Evaluating Subjects With Relapsed/Refractory Mantle Cell Lymphoma (ZUMA-2)" at ClinicalTrials.gov
  • Clinical trial number NCT02614066 for "A Study Evaluating Brexucabtagene Autoleucel (KTE-X19) in Adult Subjects With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (ZUMA-3) (ZUMA-3)" at ClinicalTrials.gov