On October 1, 2021, the CD19-directed chimeric antigen receptor (CAR) T-cell therapy brexucabtagene autoleucel was approved for adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).1
The product is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Yescarta and Tecartus REMS Program.
Supporting Efficacy Data
Approval was based on findings in the multicenter phase I/II ZUMA-3 trial (ClinicalTrials.gov identifier NCT02614066), in which 54 evaluable patients received a single intravenous (IV) infusion at a target dose of 1 × 106 anti-CD19 CAR T cells/kg (maximum = 1 × 108 cells) after completing lymphodepleting chemotherapy.
Brexucabtagene autoleucel has a boxed warning for cytokine-release syndrome and neurologic toxicities, including life-threatening reactions.
Complete response within 3 months of infusion was observed in 28 patients (51.9%, 95% confidence interval [CI] = 37.8%–65.7%). After a median follow-up for responders of 7.1 months, the median duration of complete response was not reached (95% CI = 9.6 months to not evaluable; range = 0.03+ to 16.07+ months).
How It Is Used
The recommended dose in ALL is a single IV infusion of 1 × 106 CAR T cells/kg (maximum = 1 × 108 CAR T cells) after fludarabine/cyclophosphamide lymphodepleting chemotherapy.
The product must be administered at a certified health-care facility. Patients should be monitored at the facility for at least 14 days following infusion for signs and symptoms of cytokine-release syndrome and neurologic events and instructed to remain within proximity of the facility for at least 4 weeks.
Product labeling provides instructions on required premedication and instructions on treatment and management of cytokine-release syndrome and neurologic toxicity.
Among 78 patients receiving brexucabtagene autoleucel in the ZUMA-3 study, the most common adverse events of any grade (≥ 30%) were fever (96%), cytokine-release syndrome (92%), hypotension (69%), encephalopathy (63%), tachycardia (63%), nausea (41%), chills (40%), headache (38%), fatigue (37%), febrile neutropenia (35%), diarrhea (32%), musculoskeletal pain (32%), and hypoxia (31%). The most common grade ≥ 3 adverse events were fever (38%), febrile neutropenia (35%), hypotension (33%), encephalopathy (27%), cytokine-release syndrome (26%), hypoxia (23%), and infection-pathogen unspecified (22%). Neurologic toxicities of any grade occurred in 87% and were grade ≥ 3 in 35%. The most common grade 3 or 4 laboratory abnormalities apart from cytopenias (77%–99%) were hypophosphatemia (47%) and increased alanine aminotransferase (31%). Fatal adverse events occurred in four patients (5%), including cerebral edema, sepsis, and fungal pneumonia.
Brexucabtagene autoleucel has a boxed warning for cytokine-release syndrome and neurologic toxicities, including life-threatening reactions. The product has warnings/precautions for hemophagocytic lymphohistiocytosis/macrophage activation syndrome, hypersensitivity reactions, severe infections, prolonged cytopenias, hypogammaglobulinemia, secondary malignancies, and effects on ability to drive and use machines.
1. Tecartus (brexucabtagene autoleucel) suspension for intravenous infusion prescribing information, Kite Pharma, Inc. Available at https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/tecartus-brexucabtagene-autoleucel. Accessed October 25, 2021.