The U.S. Food and Drug Administration (FDA) has approved CD19-directed chimeric antigen receptor (CAR) T-cell therapy brexucabtagene autoleucel for the treatment of adult patients with relapsed or refractory B-cell precursor acute lymphocytic leukemia (ALL).
This decision is based on data from the single-arm multicenter ZUMA-3 trial (NCT02614066). Patients received a single intravenous (IV) infusion of brexucabtagene autoleucel after completion of lymphodepleting chemotherapy. Of 54 evaluable patients, 28 achieved complete response (CR) within three months of infusion (52%; 95% CI 38%-66%). The median duration of CR was not reached at a median follow-up of 7.1 months, but was estimated to exceed 12 months for more than half of patients.
Adverse events (AEs) reported in â‰¥20% of patients were fever, cytokine release syndrome (CRS), hypotension, encephalopathy, tachycardias, nausea, chills, headache, fever, febrile neutropenia, diarrhea, musculoskeletal pain, hypoxia, rash, edema, tremor, infection with pathogen unspecified, constipation, decreased appetite, and vomiting.
Recommended dosing is a single IV infusion of 1 Ã— 106 CAR-positive viable T cells per kg of body weight, with a maximum of 1 Ã— 108 CAR-positive viable T cells, following fludarabine and cyclophosphamide for lymphodepleting chemotherapy.
CRS occurred in 92% of patients who experienced AEs (grade â‰¥3, 26%) and neurologic toxicities occurred in 87% of patients who experienced AEs (grade â‰¥3, 35%). Brexucabtagene autoleucel carries a boxed warning for life threatening reactions due to CRS and neurologic toxicities.