A novel CAR T-cell therapy, obecabtagene autoleucel (obe-cel), has demonstrated promising results in treating adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). The Phase Ib/II FELIX trial, co-led by researchers at The University of Texas MD Anderson Cancer Center, revealed high response rates and a potential for durable remission, leading to FDA approval in November 2024.
High Response Rates and Survival Outcomes
The FELIX trial, published in the New England Journal of Medicine, evaluated 127 patients with relapsed or refractory CD19-positive B-cell ALL. The study reported a 76.6% overall response rate and a 55.3% complete remission rate. The median event-free survival (EFS) was 11.9 months, with EFS rates at six and 12 months being 65.4% and 49.5%, respectively. The median overall survival (OS) for infused patients was 15.6 months, with six- and 12-month OS rates of 80.3% and 61.1%, respectively.
FDA Approval and Clinical Significance
Based on the FELIX trial data, the FDA approved obe-cel for adult patients with relapsed or refractory B-cell ALL. This approval marks a significant advancement, offering a new treatment option for patients who previously had limited alternatives. According to Dr. Elias Jabbour, professor of Leukemia and the study’s U.S. lead investigator, obe-cel demonstrated strong long-term efficacy and response rates, with minimal immunotoxicity and strong CAR T-cell persistence.
Minimal Need for Stem Cell Transplantation
Among the 99 patients who responded to obe-cel, only 18 proceeded to stem cell transplantation (SCT) while in remission, suggesting a durable response from the CAR T-cell therapy. Researchers observed no significant difference in EFS and OS between patients who received SCT and those who did not, further supporting the potential for long-term remission with obe-cel alone.
Clearance of Minimal Residual Disease
The trial also demonstrated significant clearance of minimal residual disease (MRD) following obe-cel treatment. Among 68 high-risk patients (defined as those with bone marrow blasts greater than 5% prior to lymphodepletion) who achieved complete remission, 58 were MRD-negative after obe-cel infusion. Further findings, to be presented at the American Society of Hematology (ASH) Annual Meeting, will highlight the correlation between the depth of MRD-negative remission and clinical outcomes.
Safety Profile
Toxicities observed in the trial were mostly limited to patients with high bone marrow burden. While some patients experienced cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), these were generally low grade. Specifically, 75% of patients experienced CRS (3% grade 3), and 24% experienced ICANS (7% grade ≥3). Other common adverse events included infections, musculoskeletal pain, and fever. Notably, obe-cel, unlike other CAR-T therapies, does not require a Risk Evaluation and Mitigation Strategy (REMS) program.
Funded by Autolus Therapeutics, the FELIX trial represents a significant step forward in the treatment of relapsed or refractory B-cell ALL, offering hope for improved outcomes for patients with limited treatment options.
