Autolus Therapeutics has announced significant clinical updates for its CAR T-cell therapy obecabtagene autoleucel (obe-cel) in relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL), with data to be presented at the upcoming European Hematology Association (EHA) Congress in Milan, Italy, June 12-15, 2025.
The company will present three abstracts, including two oral presentations and one poster, highlighting long-term follow-up data from the FELIX clinical trial and new analyses on efficacy, safety, and predictive models for treatment outcomes.
Long-Term Remission Without Stem Cell Transplant
In a groundbreaking oral presentation titled "Can CAR T-cell therapy be a definitive treatment for adult r/r B-ALL without transplant?", Dr. Jae H. Park will present extended follow-up data showing that 40% of responders to obe-cel maintained ongoing remission for three or more years without requiring subsequent stem cell therapy or other new treatments.
The analysis identified three independent factors associated with better outcomes and longer survival: obe-cel persistence in the body, low disease burden at the time of lymphodepletion, and use of obe-cel in earlier lines of therapy.
"These findings challenge the traditional paradigm that stem cell transplantation is necessary for long-term remission in adult r/r B-ALL patients," said Dr. Park. "The durability of responses we're seeing suggests obe-cel could potentially serve as a definitive treatment for many patients."
Efficacy Across Age Groups
A second oral presentation by Dr. Bijal D. Shah will address the efficacy and safety of obe-cel across different age groups. The analysis demonstrated that obe-cel produced deep and durable remissions in both younger (<55 years) and older (≥55 years) adults with r/r B-ALL.
Importantly, the treatment showed favorable overall remission rates, event-free survival, and overall survival in both age cohorts. The incidence of Grade ≥3 cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) remained low across all age groups.
"The consistent efficacy and manageable safety profile across age groups is particularly encouraging," Dr. Shah noted. "Older adults with r/r B-ALL typically have fewer treatment options and poorer outcomes, so these results represent a significant advancement for this population."
The data is especially notable given that few patients in the study received consolidative stem cell therapy after obe-cel treatment, further supporting the potential of obe-cel as a standalone therapy.
Improving Risk Prediction Models
In a poster presentation, Dr. Claire Roddie will present research comparing different models for predicting hematotoxicity risk and outcomes in r/r B-ALL patients treated with obe-cel.
The analysis evaluated two prediction models: the CAR-Hematotox (CAR-HT) model and the ALL-Hematotox (ALL-HT) model. Results suggest that the ALL-HT model, which is disease-specific rather than CAR-specific, may better predict response, survival, and safety outcomes in patients treated with obe-cel.
"Our findings indicate that the strength of hematotoxicity model predictions may be CAR-specific," explained Dr. Roddie. "This has important implications for risk stratification and patient selection for CAR T-cell therapy."
About AUCATZYL (Obecabtagene Autoleucel)
AUCATZYL is a CD19-directed genetically modified autologous T cell immunotherapy designed with a fast target binding off-rate to minimize excessive activation of programmed T cells. This unique design feature may contribute to its efficacy and safety profile.
The therapy received FDA approval for the treatment of adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia on November 8, 2024, and was licensed by the UK's MHRA under conditional marketing authorization on April 25, 2025. A regulatory submission to the European Medicines Agency (EMA) was accepted in April 2024.
The FELIX clinical trial that supported these approvals enrolled over 100 patients across 30 leading centers in the United States, United Kingdom, and Europe. The primary endpoint was overall response rate, with secondary endpoints including duration of response, minimal residual disease (MRD) negative complete remission rate, and safety.
Safety Considerations
As with other CAR T-cell therapies, AUCATZYL carries risks of serious adverse events. The most common include cytokine release syndrome (CRS), which occurred in 75% of patients (3% Grade 3), and neurologic toxicities, reported in 64% of patients (12% Grade ≥3).
ICANS events occurred in 24% of patients, with Grade ≥3 events in 7%. Other significant adverse reactions included prolonged cytopenias, infections, hypogammaglobulinemia, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS).
Nine patients (9%) experienced fatal adverse reactions, including infections, ascites, pulmonary embolism, acute respiratory distress syndrome, HLH/MAS, and ICANS. Five of these patients had pre-existing and ongoing neutropenia prior to treatment.
Future Directions
Autolus Therapeutics continues to develop its pipeline of programmed T cell therapies for various hematological malignancies, solid tumors, and autoimmune diseases. The company's approach focuses on engineering precisely targeted and controlled T cell therapies designed to better recognize target cells, break down their defense mechanisms, and eliminate these cells.
The promising long-term data for obe-cel in r/r B-ALL represents a significant advancement in CAR T-cell therapy, potentially offering a definitive treatment option for a patient population with historically poor outcomes and limited treatment options.
Additional analyses with extended follow-up are underway and will be presented at the EHA Congress, providing further insights into the long-term efficacy and safety of this innovative therapy.
