FDA Approves Brexucabtagene Autoleucel for Relapsed or Refractory B-Cell Precursor Acute Lymphoblastic Leukemia
On October 1, 2021, the U.S. Food and Drug Administration (FDA) approved (https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-brexucabtagene-autoleucel-relapsed-or-refractory-b-cell-precursor-acute-lymphoblastic) brexucabtagene autoleucel (Tecartus™) for adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).
Efficacy was evaluated in a single-arm, multicenter trial (ZUMA-3; NCT02614066) 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.
The efficacy outcome measures used to support approval were complete response (CR) achieved within three months from infusion and duration of CR. Of the 54 patients evaluable for efficacy, 28 (52%; 95% CI = 38, 66) achieved CR within three 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 of the patients.
The prescribing information for brexucabtagene autoleucel has a boxed warning for cytokine release syndrome (CRS) and neurologic toxicities. CRS occurred in 92% (grade ≥ 3, 26%) of patients receiving brexucabtagene autoleucel, and neurologic toxicities occurred in 87% (grade ≥ 3, 35%) . The most common nonlaboratory adverse reactions reported in 20% or more of patients were fever, CRS, hypotension, encephalopathy, tachycardias, nausea, chills, headache, fatigue, febrile neutropenia, diarrhea, musculoskeletal pain, hypoxia, rash, edema, tremor, infection with unspecified pathogen, constipation, decreased appetite, and vomiting.
The recommended brexucabtagene autoleucel dose is a single IV infusion of 1 x 106 CAR-positive viable T cells per kg body weight (maximum 1 x 108 CAR-positive viable T cells), preceded by fludarabine and cyclophosphamide as lymphodepleting chemotherapy.
The review used the Assessment Aid (https://www.fda.gov/about-fda/oncology-center-excellence/assessment-aid), a voluntary submission from the applicant to facilitate FDA’s assessment.
FDA granted the application priority review, breakthrough designation, and orphan drug designation. A description of FDA expedited programs is in the Guidance for IndustryꟷExpedited Programs for Serious ConditionsꟷDrugs and Biologics (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/expedited-programs-serious-conditions-drugs-and-biologics).
Healthcare professionals should report all serious adverse events they suspect are associated with the use of any medicine and device to FDA’s MedWatch Reporting System (https://www.accessdata.fda.gov/scripts/medwatch/index.cfm) or by calling 800-FDA-1088.
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate (https://www.fda.gov/about-fda/oncology-center-excellence/project-facilitate) at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov (mailto:OncProjectFacilitate@fda.hhs.gov).