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 (ALL). This decision marks a significant advancement in the treatment landscape for this aggressive cancer, addressing a critical unmet need for patients who relapse after initial therapies. The approval was announced on November 8, 2024, offering new hope to adult patients facing this challenging disease.
The approval is based on data from the phase 1/2 FELIX trial (NCT04404660), a pivotal study evaluating the safety and efficacy of obe-cel in adult patients with relapsed or refractory B-cell ALL. The study enrolled patients aged 18 years or older with relapsed/refractory B-cell ALL who had a bone marrow blast level of at least 5%. Key findings from the FELIX trial demonstrated a complete remission (CR) rate of 42% (95% CI, 29%-54%) within 3 months of treatment among evaluable patients (n = 65). The median duration of CR for those who responded within 3 months was 14.1 months (95% CI, 6.1–not reached).
Clinical Efficacy and Safety Profile
The FELIX trial's primary endpoint was the CR/CR with incomplete count recovery (CRi) rate. Secondary endpoints included duration of response, event-free survival, overall survival, minimal residual disease–negativity rate, and safety. The results showcased a promising efficacy signal, leading to the FDA's decision to approve obe-cel for this patient population.
Daniel DeAngelo, MD, PhD, from Dana-Farber Cancer Institute, emphasized the significance of the durable remission rates observed with obe-cel, highlighting its potential as a transformative option for patients with relapsed/refractory CD19-positive B-cell ALL. He noted that this approval makes obe-cel the third FDA-approved CAR T-cell therapy in B-cell precursor ALL, marking a significant development in the ALL treatment paradigm.
Regarding safety, cytokine release syndrome (CRS) occurred in 68.5% of patients who received at least 1 dose of the CAR T-cell therapy; the rate of with grade 3 or higher CRS was 2.4%. Immune effector cell–associated neurotoxicity syndrome (ICANS) occurred in 22.8% of patients at any grade and 7.1% of patients at grade 3 or higher.
Dosage and Administration
Obe-cel is recommended at a dose of 410 X 106 CD19 CAR-positive T cells, administered as a split-dose infusion on days 1 and 10 (±2 days), based on bone marrow blast assessment. Prior to the infusion of obe-cel, patients undergo lymphodepleting chemotherapy with fludarabine and cyclophosphamide. Specifically, patients receive 30 mg/m2 of fludarabine for 4 days plus 500 mg/m2 of cyclophosphamide for 2 days, starting on day -6.
For patients with a bone marrow blasts level of 20% or less, the day 1 infusion is 100 x 106 CAR T cells; if patients do not experience grade 3 or higher CRS or any-grade ICANS, they receive 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 is 10 x 106 CAR T cells; the day 10 dose is 400 x 106 CAR T cells if patients do not experience grade 3 or higher CRS or any-grade ICANS. Notably, 94% of infused patients received both doses during FELIX.
Boxed Warning and Precautions
The prescribing information for obe-cel includes a boxed warning for CRS, ICANS, and T-cell malignancies. Healthcare providers should monitor patients closely for signs and symptoms of these adverse reactions and manage them according to established guidelines.
Expert Commentary
Elias Jabbour, MD, United States lead investigator of the FELIX study, stated that the approval of obe-cel brings new hope for adult patients with relapsed/refractory B-cell ALL, addressing a high unmet medical need in this patient population.
