Brexucabtagene Autoleucel
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Brexucabtagene autoleucel, sold under the brand name Tecartus, is a cell-based gene therapy medication for the treatment of
mantle cell lymphoma Mantle cell lymphoma (MCL) is a type of non-Hodgkin's lymphoma (NHL), comprising about 6% of NHL cases. There are only about 15,000 patients presently in the United States with mantle cell lymphoma. It is named for the mantle zone of the lymph n ...
(MCL) and acute lymphoblastic leukemia (ALL). The most common side effects include serious infections, low blood cell counts and a weakened immune system. 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. Brexucabtagene autoleucel is a
chimeric antigen receptor T cell 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 specifi ...
therapy and is the first cell-based
gene therapy Gene therapy is a medical field which focuses on the genetic modification of cells to produce a therapeutic effect or the treatment of disease by repairing or reconstructing defective genetic material. The first attempt at modifying human DN ...
approved by the U.S.
Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
(FDA) for the treatment of mantle cell lymphoma. Brexucabtagene autoleucel was approved for medical use in the United States in July 2020, and in the European Union in December 2020.


Medical uses

Brexucabtagene autoleucel is indicated for the treatment of adults with relapsed or refractory mantle cell lymphoma. It is also indicated for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia. Mantle cell lymphoma (MCL) is a rare form of cancerous B-cell
non-Hodgkin's lymphoma Non-Hodgkin lymphoma (NHL), also known as non-Hodgkin's lymphoma, is a group of hematological malignancy, blood cancers that includes all types of lymphomas except Hodgkin lymphomas. Symptoms include lymphadenopathy, enlarged lymph nodes, fever ...
that usually occurs in middle-aged or older adults. 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. Each dose of brexucabtagene autoleucel is a customized treatment created using the recipient's own immune system to help fight the lymphoma. The recipient's
T cell A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...
s, 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. These modified T cells are then infused back into the recipient.


Side 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. Both cytokine release syndrome and neurologic toxicities can be fatal or life-threatening. The most common side effects of brexucabtagene autoleucel include serious infections, low blood cell counts and a weakened immune system. Side effects from treatment usually appear within the first one to two weeks after treatment, but some side effects may occur later. 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. Because of the risk of cytokine release syndrome and neurological toxicities, brexucabtagene autoleucel was approved with a
risk evaluation and mitigation strategy Risk Evaluation and Mitigation Strategies (REMS) is a program of the US Food and Drug Administration for the monitoring of medications with a high potential for serious adverse effects. REMS applies only to specific prescription drugs, but can apply ...
(REMS), which includes elements to assure safe use. The risk mitigation measures for brexucabtagene autoleucel are identical to those of the REMS Program for another CAR-T therapy,
axicabtagene ciloleucel 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. T cells are removed from a person with lymphoma and genetically engineered to p ...
(Yescarta).


History

Brexucabtagene autoleucel was approved for medical use in the United States in July 2020. 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. Participants received a single infusion of brexucabtagene autoleucel following completion of lymphodepleting chemotherapy. The primary efficacy outcome measure was objective response rate (ORR) per Lugano
014 014 may refer to: * Argus As 014 * BIND-014 * 014 Construction Unit * Divi Divi Air Flight 014 * Pirna 014 * Tyrrell 014 The Tyrrell 014 was a Formula One car, designed for Tyrrell Racing by Maurice Philippe for use in the season. The cars wer ...
criteria as assessed by an independent review committee. The complete remission rate after treatment with brexucabtagene autoleucel was 62 percent, with an objective response rate of 87 percent. The application for brexucabtagene autoleucel was approved under the
accelerated approval The United States Food and Drug Administration (FDA) initiated the FDA Accelerated Approval Program in 1992 to allow faster approval of drugs for serious conditions that fill an unmet medical need. The faster approval relies on use of surrogate endp ...
pathway and it was granted
priority review Priority review is a program of the United States Food and Drug Administration (FDA) to expedite the review process for drugs that are expected to have a particularly great impact on the treatment of a disease. The priority review voucher program ...
,
breakthrough therapy Breakthrough therapy is a United States Food and Drug Administration designation that expedites drug development that was created by Congress under Section 902 of the 9 July 2012 Food and Drug Administration Safety and Innovation Act. The FDA's "br ...
, and orphan drug designations. 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. Participants received a single infusion of brexucabtagene autoleucel following completion of lymphodepleting chemotherapy.


References


Further reading

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External links

* * {{DEFAULTSORT:Brexucabtagene Autoleucel Breakthrough therapy Cancer treatments Gene therapy Gilead Sciences Orphan drugs