Promising Results from the FELIX Trial
Obecabtagene autoleucel (obe-cel), a novel anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, has shown exceptional efficacy and safety in treating relapsed or refractory CD19-positive B-cell acute lymphoblastic leukemia (B-cell ALL). Findings from the Phase Ib/II FELIX trial, co-led by The University of Texas MD Anderson Cancer Center, revealed a 76.6% response rate and a 55.3% complete remission rate in 127 patients. Published in the New England Journal of Medicine, the trial reported a median event-free survival (EFS) of 11.9 months, with six- and 12-month EFS rates at 65.4% and 49.5%, respectively. The median overall survival (OS) was 15.6 months, with six- and 12-month OS rates of 80.3% and 61.1%.
These promising results led to the U.S. Food and Drug Administration’s approval of obe-cel in November 2024 for treating adult patients with relapsed or refractory B-cell ALL. Elias Jabbour, M.D., the study’s U.S. lead investigator, noted, “Until now, patients with B-cell ALL had limited treatment options. Obecabtagene autoleucel provides a much-needed standalone solution with strong efficacy, minimal immunotoxicity, and sustained CAR T-cell persistence.” Further insights from the FELIX trial will be presented at the 2024 American Society of Hematology (ASH) Annual Meeting.
Trial Design and Patient Outcomes
The global, multi-center FELIX trial enrolled 127 adult patients with relapsed or refractory B-cell ALL. Participants underwent lymphodepletion to prepare for CAR T-cell infusion, followed by split obe-cel doses on days one and 10. The median age of participants was 47, with 52% identifying as male. Patients exhibited diverse racial backgrounds, with 74% identifying as white, 12.6% as Asian, 1.6% as Black, and 11.8% unspecified.
Toxicities associated with obesity were limited, primarily affecting patients with high bone marrow burden. Incidents of cytokine release syndrome (CRS) and neurotoxicity, common in CAR T-cell therapies, were minimal, with only three cases of grade 3 or higher CRS and nine cases of grade 3 or higher neurotoxicity. Researchers found that these side effects were consistent with prior CAR T-cell studies, with no new adverse effects identified.
Among the 99 responders, only 18 required a subsequent stem cell transplant (SCT) while in remission. Remarkably, there was no significant difference in EFS and OS between those who underwent SCT and those who did not, suggesting the durability of Obecabtagene autoleucel’s therapeutic effects.
Minimal Residual Disease Clearance and Future Implications
The trial highlighted the significant reduction of minimal residual disease (MRD)—a key indicator of relapse risk—in patients treated with obe-cel. Of the 68 high-risk patients with more than 5% bone marrow blasts before treatment, 62 had MRD data available. An overwhelming 58 of these patients achieved MRD-negative status after therapy, emphasizing Obecabtagene autoleucel’s ability to deliver deep and durable remissions.
In preparation for the upcoming ASH meeting, researchers analyzed bone marrow samples using next-generation sequencing (NGS) to explore the link between MRD clearance and clinical outcomes. According to Jabbour, lower MRD levels correlated strongly with higher EFS and OS rates, reinforcing the value of obe-cel as a transformative treatment for B-cell ALL.
The findings mark a significant advancement in leukemia therapy, offering new hope to patients with limited options. Obe-cel’s strong efficacy, manageable side effects, and long-lasting results position it as a potential standard of care for relapsed or refractory B-cell ALL.
