Obecabtagene Autoleucel Approved for Relapsed or Refractory B-Cell Precursor Acute Lymphoblastic Leukemia
Expert Perspectives · Lyn Brook · 2024-11-12
The FDA has approved obecabtagene autoleucel (Aucatzyl®, Autolus Inc.), a CD19-directed genetically modified autologous T-cell immunotherapy, for adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).
Why is the Obecabtagene Autoleucel Approval Important?
“Obecabtagene autoleucel is an autologous CD19CAR with a fast off-rate CD19 binding domain designed to reduce chimeric antigen receptor (CAR) T immunotoxicity and improve persistence,” wrote Claire Roddie, MD, an Associate Professor of Hematology-Oncology at the University College London, and colleagues in their published results of the FELIX trial (NCT04404660). “Its clinical activity has been tested in relapsed or refractory pediatric and adult B-ALL trials and more recently in adults with relapsed or refractory B-cell malignancies.”
Evaluating Obecabtagene Autoleucel in the FELIX Trial
Efficacy of obecabtagene autoleucel was measured in the open-label, multicenter, single-arm FELIX study that included adult patients with relapsed or refractory CD19-positive B-cell ALL. To be eligible, patients had to meet one of the following criteria: disease relapse after a remission of 12 months or less, relapse or resistance following at least two lines of systemic therapy, or relapse or resistance three or more months after an allogeneic stem cell transplant.
The primary efficacy measure was the rate and duration of complete remission (CR) achieved within three months after infusion. Additional outcomes included overall complete remission rates, combining CR and complete remission with incomplete hematologic recovery (CRi) at any point during treatment.
Among the 65 patients evaluated, 27 (42%) achieved CR within three months, with a median CR duration of 14.1 months.
Adverse Events
The prescribing information for obecabtagene autoleucel includes a boxed warning for cytokine release syndrome (CRS), immune effector cell–associated neurotoxicity syndrome (ICANS), and T-cell malignancies. CRS, a systemic inflammatory response caused by CAR T therapies, occurred in 75% of patients (with grade 3 severity in 3% of cases), while neurologic toxicities affected 64% of patients, including ICANS in 24% (with grade ≥3 severity in 7% of cases).
The most common non-laboratory adverse events occurring in ≥20% of patients included CRS, infections-pathogen unspecified, musculoskeletal pain, viral infections, fever, nausea, bacterial infectious disorders, diarrhea, febrile neutropenia, ICANS, hypotension, pain, fatigue, headache, encephalopathy, and hemorrhage.
Putting It Into Context
“The prespecified interim analysis of the FELIX study demonstrated that obecabtagene autoleucel for adult relapsed or refractory B-ALL is safe with low rates of grade >3 CRS and/or ICANS, even in patients with high-burden disease,” concluded Dr. Roddie and colleagues. “Obecabtagene autoleucel is effective with high CR/CRi rates and ongoing CAR T persistence in the majority of responders.”
Dosing Instructions
The recommended dose of obecabtagene autoleucel is 410 x 106 CD19 CAR-positive viable T cells, administered as a split dose infusion. Patients receive this treatment on Day 1 and Day 10 (±2 days), with dosing adjusted based on bone marrow blast assessment. Before receiving the CAR T infusion, patients undergo lymphodepleting chemotherapy with fludarabine and cyclophosphamide.