FDA Approves Obecabtagene Autoleucel (Obe-cel) for Relapsed/Refractory B-Cell ALL
核心洞察
The FDA has approved obecabtagene autoleucel (obe-cel; Aucatzyl) for adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (搜索) (ALL).
The approval was based on the phase 1/2 FELIX trial, which demonstrated a 42% complete remission rate within 3 months among evaluable patients.
Obe-cel is administered as a split-dose infusion on days 1 and 10, following lymphodepletion with fludarabine and cyclophosphamide.
The FDA has granted approval to obecabtagene autoleucel (obe-cel; Aucatzyl) for the treatment of adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (搜索) (ALL). This approval marks a significant advancement for patients facing this aggressive cancer, addressing a critical unmet need in cases of relapse where historical outcomes have been poor.
The decision was supported by data from the phase 1/2 FELIX trial (NCT04404660), a study evaluating the efficacy and safety of obe-cel in adult patients with relapsed/refractory B-cell ALL (搜索). The study enrolled patients aged 18 years and older with relapsed/refractory B-cell ALL and a bone marrow blast level of at least 5%.
Efficacy Results from FELIX Trial
Data from the FELIX trial showed promising results. Among evaluable patients (n = 65), the complete remission (CR) rate within 3 months of treatment was 42% (95% CI, 29%-54%). The median duration of CR for those who responded within 3 months was 14.1 months (95% CI, 6.1–not reached).
Topline data presented at the 2023 ASCO Annual Meeting showed that evaluable patients (n = 94) achieved an overall response rate of 76% (95% CI, 66%-84%; P < .0001). The CR and CRi rates were 54.3% and 21.3%, respectively. The median DOR was 14.1 months (95% CI, 5.9–not evaluable).
Dosing and Administration
Obe-cel is administered as a split-dose infusion on day 1 and day 10, following lymphodepletion. Lymphodepletion is conducted with 30 mg/m2 of fludarabine for 4 days plus 500 mg/m2 of cyclophosphamide for 2 days, starting on day -6. The recommended dose of Obe-cel is 410 X 106 CD19 CAR-positive T cells given as a split-dose infusion on days 1 and 10 (±2 days), based on bone marrow blast assessment.
For patients with a bone marrow blasts level of 20% or less, the day 1 infusion was 100 x 106 CAR T cells; if patients did not experience grade 3 or higher cytokine release syndrome (CRS (搜索)) or any-grade immune effector cell–associated neurotoxicity syndrome (ICANS (搜索)), they received 310 x 106 CAR T cells on day 10. For those with a bone marrow blasts level of more than 20%, the day 1 infusion was 10 x 106 CAR T cells; the day 10 dose was 400 x 106 CAR T cells if patients did not experience grade 3 or higher CRS or any-grade ICANS. Notably, 94% of infused patients received both doses during FELIX.
Safety Profile
Safety data from the FELIX trial indicated that the rate of any-grade CRS (搜索) was 75%, with a grade 3 CRS rate of 3%. Any-grade neurologic toxicities occurred in 64% of patients, including ICANS (搜索) at a rate of 24%. The grade 3 rates of neurologic toxicities and ICANS were 12% and 7%, respectively.
The most common non-laboratory adverse effects reported in at least 20% of patients included CRS (搜索), infections-pathogen unspecified, musculoskeletal pain, viral infections, fever, nausea, bacterial infectious disorders, diarrhea, febrile neutropenia, ICANS (搜索), hypotension, pain, fatigue, headache, encephalopathy, and hemorrhage.
The prescribing information includes a boxed warning for CRS (搜索), ICANS (搜索), and T-cell malignancies.