Brief Introduction of CAR-T Cell Therapy Brexucabtagene Autoleucel(Tecartus)
Brief Introduction of CAR-T Cell Therapy Brexucabtagene Autoleucel(Tecartus)
Brexucabtagene Autoleucel Receives First Marketing Approval
On July 24, 2020, the U.S. Food and Drug Administration (FDA) granted accelerated approval for Brexucabtagene Autoleucel (Tecartus), a CD19-directed, genetically modified autologous T-cell immunotherapy, for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL).
The approval was based on the open-label, multicenter, single-arm ZUMA-2 trial (NCT02601313).
The trial involved 74 patients with relapsed or refractory mantle cell lymphoma, all of whom had previously received chemotherapy containing anthracyclines or bendamustine, an anti-CD20 antibody, and a Bruton’s tyrosine kinase inhibitor.
After completing lymphodepleting chemotherapy, all patients received a single infusion of Brexucabtagene Autoleucel.
The primary efficacy endpoint was the objective response rate (ORR) assessed by an independent review committee using the Lugano [2014] criteria.
At a minimum follow-up time of 6 months for response, the ORR was 87% (52/60 evaluable patients), with a complete response (CR) rate of 62%.
With a median follow-up (for remission duration) of 8.6 months, the median duration of response was not reached (range: 0+ to 29.2+ months).
In all 74 leukemia patients, the ORR assessed by the independent review committee (IRC) was 80%, and the CR rate was 55%.
The most common (≥10%) Grade 3 or higher adverse reactions were anemia, neutropenia, thrombocytopenia, hypotension, hypophosphatemia, encephalopathy, leukopenia, hypoxia, fever, hyponatremia, hypertension, infection–unspecified pathogen, pneumonia, hypocalcemia, and lymphopenia. Due to the potential life-threatening risks of cytokine release syndrome (CRS) and neurological toxicities, the FDA approved Brexucabtagene Autoleucel with a risk evaluation and mitigation strategy.
Dosage and Administration of Brexucabtagene Autoleucel
The recommended dosage of Tecartus is 2 × 10^6 CAR-positive viable T cells per kg body weight, with a maximum of 2 × 10^8 CAR-positive viable T cells.
Prior to Tecartus infusion, on the 5th, 4th, and 3rd days, administer a lymphodepleting chemotherapy regimen of cyclophosphamide 500 mg/m^2 and fludarabine 30 mg/m^2 intravenously.
Premedicate with acetaminophen and diphenhydramine or another H1-antihistamine approximately 30 to 60 minutes before Tecartus infusion. Avoid prophylactic use of systemic corticosteroids.
Brexucabtagene Autoleucel Receives Additional Approval
In October 2021, the U.S. Food and Drug Administration (FDA) approved the CAR-T cell therapy Brexucabtagene Autoleucel (Tecartus) for the treatment of relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL). This approval made Brexucabtagene Autoleucel the first CAR-T cell therapy approved for adult ALL.