The U.S. Food and Drug Administration (FDA) approved the CD19-directed genetically modified autologous T-cell immunotherapy obecabtagene autoleucel (Aucatzyl) for adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).
Efficacy and Safety
Efficacy was evaluated in FELIX (ClinicalTrials.gov identifier NCT04404660), an open-label, multicenter, single-arm trial that enrolled adults with relapsed or refractory CD19-positive B-cell ALL. Enrolled patients were required to have relapsed following a remission lasting 12 months or less, relapsed or refractory ALL following two or more prior lines of systemic therapy, or disease that was relapsed or refractory 3 or more months after allogeneic stem cell transplantation.
The major efficacy outcome measures were rate and duration of complete remission achieved within 3 months after infusion. Additional outcome measures were rate and duration of overall complete remission which includes complete remission and complete remission with incomplete hematologic recovery, at any time. Of the 65 patients evaluable for efficacy, 27 patients (42%, 95% confidence interval [CI] = 29%–54%) achieved complete remission within 3 months. The median duration of complete remission achieved within 3 months was 14.1 months (95% CI = 6.1 to not reached).
The prescribing information has a boxed warning for cytokine-release syndrome, immune effector cell–associated neurotoxicity syndrome (ICANS) and T-cell malignancies. Cytokine-release syndrome occurred in 75% (grade 3, 3%), and neurologic toxicities occurred in 64% (grade ≥ 3, 12%), including ICANS in 24% (grade ≥ 3, 7%). The most common nonlaboratory adverse reactions (incidence ≥ 20%) included cytokine-release syndrome, infections–pathogen unspecified, musculoskeletal pain, viral infections, fever, nausea, bacterial infectious disorders, diarrhea, febrile neutropenia, ICANS, hypotension, pain, fatigue, headache, encephalopathy, and hemorrhage.
The approval was announced on November 8, 2024.
