On July 24, the U.S. Food and Drug Administration (FDA) granted accelerated approval to 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.
“Tremendous progress has been made in the discovery of new therapies for debilitating diseases that are difficult to treat. This approval is yet another example of customized treatments that use a patient’s own immune system to help fight cancer, while using a scientific advance in this promising new area of medicine,” said Peter Marks, MD, PhD, Director of the FDA’s Center for Biologics Evaluation and Research. “We’re seeing continued advances in the field of gene therapy and remain committed to supporting innovation in this promising new area of medicine.”
Approval was based on ZUMA-2, an open-label, multicenter, single-arm trial of 74 patients with relapsed or refractory mantle cell lymphoma who had previously received anthracycline- or bendamustine-containing chemotherapy, an anti-CD20 antibody, and a Bruton’s tyrosine kinase inhibitor. Patients received a single infusion of brexucabtagene autoleucel following completion of lymphodepleting chemotherapy. The primary efficacy outcome measure was objective response rate per Lugano (2014) criteria as assessed by an independent review committee.
Of the 60 patients evaluable for efficacy based on a minimum duration of follow-up for response of 6 months, the objective response rate was 87% (95% confidence interval [CI] = 75–94), with a complete remission rate of 62% (95% CI = 48–74). The estimated median duration of response was not reached (range of 0+ to 29.2+ months) after a median follow-up time for duration of response of 8.6 months. Of all 74 leukapheresed patients, the objective response rate as assessed by independent review committee was 80% (95% CI = 69–88), with a complete response rate of 55% (95% CI = 43–67).
The most common (reported in ≥ 10% of patients) grade 3 or higher reactions were anemia, neutropenia, thrombocytopenia, hypotension, hypophosphatemia, encephalopathy, leukopenia, hypoxia, pyrexia, hyponatremia, hypertension, infection (pathogen unspecified), pneumonia, hypocalcemia, and lymphopenia. The FDA also approved brexucabtagene autoleucel with a Risk Evaluation and Mitigation Strategy due to the risk of cytokine-release syndrome and neurologic toxicities.
The recommended dose of brexucabtagene autoleucel is a single intravenous infusion of 2 x 106 chimeric antigen receptor (CAR)-positive viable T cells per kg body weight (maximum 2 x 108 CAR-positive viable T cells), preceded by fludarabine and cyclophosphamide lymphodepleting chemotherapy.