On 1 October 2021, the US Food and Drug Administration (FDA) approved brexucabtagene autoleucel (Tecartus, Kite Pharma, Inc.) for adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukaemia (ALL).<\/p>\n
Efficacy was evaluated in ZUMA-3 (NCT02614066), a single-arm multicentre study that evaluated brexucabtagene autoleucel, a CD19-directed chimeric antigen receptor (CAR) T-cell therapy, in adults with relapsed or refractory B-cell precursor ALL. Patients received a single infusion of brexucabtagene autoleucel following completion of lymphodepleting chemotherapy.<\/p>\n
The efficacy outcome measures used to support approval were complete response (CR) achieved within 3 months from infusion and duration of CR. Of the 54 patients evaluable for efficacy, 28 (52%; 95% confidence interval [CI] 38, 66) achieved CR within 3 months. With a median follow-up for responders of 7.1 months, the median duration of CR was not reached; the duration of CR was estimated to exceed 12 months for more than half the patients.<\/p>\n
The prescribing information for brexucabtagene autoleucel has a boxed warning for cytokine release syndrome (CRS) and neurologic toxicities. CRS occurred in 92% (Grade \u22653, 26%) and neurologic toxicities occurred in 87% (Grade \u22653, 35%). The most common non-laboratory adverse reactions (incidence \u2265 20%) included fever, CRS, hypotension, encephalopathy, tachycardias, nausea, chills, headache, fatigue, febrile neutropenia, diarrhoea, musculoskeletal pain, hypoxia, rash, oedema, tremor, infection with pathogen unspecified, constipation, decreased appetite, and vomiting.<\/p>\n
The recommended brexucabtagene autoleucel dose is a single intravenous infusion of 1 x 106<\/sup> CAR-positive viable T cells per kg body weight (maximum 1 x 108<\/sup> CAR-positive viable T cells), preceded by fludarabine and cyclophosphamide for lymphodepleting chemotherapy.<\/p>\n The full prescribing information for Tecartus will be posted here<\/a>.<\/p>\n This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA\u2019s assessment.<\/p>\n This application was granted priority review, breakthrough designation and orphan drug designation.<\/p>\n Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA\u2019s MedWatch Reporting System.<\/p>\n For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact FDA Oncology Center of Excellence<\/a> Project Facilitate<\/a>.<\/p>\n