The FDA has approved brexucabtagene autoleucel (TecartusTM, Kite Pharma), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, for patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).
"Despite treatment with novel therapies and allogeneic stem cell transplant consolidation, outcomes in adult patients with relapsed or refractory B-cell precursor ALL remain poor, underlining the need for more effective therapies," wrote Bijal D. Shah, MD, Associate Member in the Department of Malignant Hematology at Moffitt Cancer Center, and colleagues, in their publication of results of the phase 2 ZUMA-3 trial (NCT02614066), on which the approval was based.
The single-arm multicenter trial enrolled 71 patients with relapsed or refractory B-cell precursor ALL, 54 of whom were evaluable for efficacy analysis. Patients underwent leukapheresis and conditioning chemotherapy, followed by a single 1x106/kg infusion of brexucabtagene autoleucel. The primary end point was the rate of overall complete remission or complete remission with incomplete hematological recovery achieved within 3 months of infusion. Secondary end points included overall survival, duration of remission, duration of relapse-free survival, minimal residual disease (MRD) negativity rate, and allogeneic stem cell transplant rate.
Among patients evaluable for efficacy, 52% achieved a complete response within 3 months of infusion. At a median follow-up of 7.1 months, the median duration of complete response had not been reached. In more than half of patients receiving brexucabtagene autoleucel, the duration of complete response was estimated to exceed 12 months.
Non-laboratory adverse events occurring in at least 20% of patients receiving brexucabtagene autoleucel included fever, cytokine release syndrome (CRS), hypotension, encephalopathy, tachycardias, nausea, chills, headache, fatigue, febrile neutropenia, diarrhea, musculoskeletal pain, hypoxia, rash, edema, tremor, infection with pathogen unspecified, constipation, decreased appetite, and vomiting. The prescribing information includes a boxed warning for CRS and neurologic toxicities. Neurologic toxicities occurred in 87% of patients receiving brexucabtagene autoleucel, with 35% experiencing grade 3 or higher; CRS occurred in 92% of patients, with 26% experiencing grade 3 or higher.
"[Brexucabtagene autoleucel] showed a high rate of complete remission or complete remission with incomplete hematological recovery in adult patients with relapsed or refractory B-cell precursor ALL, with the median overall survival not reached in responding patients, and a manageable safety profile," concluded Dr. Shah and colleagues in their August 2021 publication in The Lancet. "These findings indicate that [brexucabtagene autoleucel] has the potential to confer long-term clinical benefit to these patients."
The recommended dose of brexucabtagene autoleucel is a single intravenous infusion of 1x106 CAR-positive viable T cells per kg of body weight, with a maximum infusion of 1x108 CAR-positive T cells. Brexucabtagene autoleucel infusion should be preceded by lymphodepleting chemotherapy with fludarabine and cyclophosphamide.
For More Information
Shah BD, Ghobadi A, Oluwole OO, et al (2021). KTE-X19 for relapsed or refractory adult B-cell acute lymphoblastic leukaemia: phase 2 results of the single-arm, open-label, multicentre ZUMA-3 study. Lancet, 398(10299):491-502. DOI:10.1016/S0140-6736(21)01222-8
Clinicaltrials.gov (2021). A study evaluating brexucabtagene autoleucel (KTE-X19) in adult subjects with relapsed/refractory B-precursor acute lymphoblastic leukemia (ZUMA-3) (ZUMA-3). NLM identifier: NCT02614066.
TecartusTM (brexucabtagene autoleucel) prescribing information (2021). Kite Pharma. Available at: https://www.fda.gov/media/140409/download
US Food & Drug Administration (2021). FDA approves brexucabtagene autoleucel for relapsed or refractory B-cell precursor acute lymphoblastic leukemia. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-brexucabtagene-autoleucel-relapsed-or-refractory-b-cell-precursor-acute-lymphoblastic
Image credit: James Grellier. Licensed under CC BY-SA 3.0