Efficacy and safety outcomes of obecabtagene autoleucel (obe-cel) stratified by age in patients (pts) with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL).
Year: 2025
Type: conference-abstract
Abstract: 6576 Background: CD19 chimeric antigen receptor T-cell therapy (CAR T) exhibits good efficacy in adults with R/R B-ALL but is associated with higher toxicity with increasing age. Obe-cel, an autologous anti-CD19 CAR T, has shown high and durable response rates with low incidence of immunotoxicity in adult R/R B-ALL, and was recently approved by the US FDA. Here, we report a post-hoc analysis of the Phase Ib/II FELIX trial (NCT04404660) evaluating efficacy, safety, and persistence outcomes with obe-cel stratified by pt age. Methods: Adult R/R B-ALL pts received obe-cel using a tumor burden-guided dosing strategy to minimize toxicity. Overall remission rate (ORR; complete remission [CR]/CR with incomplete hematologic recovery), event-free survival (EFS), safety, and persistence are reported for pts aged <55 and ≥55 years (yrs; data cut-off: 7 Feb 2024). Results: Of 127 obe-cel infused pts, 79 (62.2%) were aged <55 yrs (median 36.0 [range: 20–54]) and 48 (37.8%) were aged ≥55 yrs (median 65.0 [range: 55–81]). A higher proportion of pts aged <55 yrs were Hispanic/Latino (36.7% vs 18.8%), had extramedullary disease at lymphodepletion (LD; 29.1% vs 8.3%), received prior blinatumomab (53.2% vs 22.9%), and prior inotuzumab ozogamicin (35.4% vs 25.0%) than those ≥55 yrs, while a higher proportion of pts aged ≥55 yrs had Philadelphia chromosome-positive disease (47.9% vs 16.5%). Median bone marrow blast burden at LD was higher in pts aged ≥55 yrs (45.5%) vs <55 yrs (30.0%). At 21.5 months’ (mos) median follow-up (range: 8.6–41.4), the ORR (95% CI) was 72.2% (60.9–81.7) in pts aged <55 yrs vs 87.5% (74.8–95.3) in pts aged ≥55 yrs. In responders, 84.2% of pts <55 yrs and 83.3% ≥55 yrs with ≥1 post-infusion next-generation sequencing result achieved measurable residual disease-negative remission to 10 –6 leukemic cells by Month 3. Durable remission at 1 yr post infusion was observed in 68.3% and 51.8% of pts aged <55 and ≥55 yrs, respectively. EFS was comparable in pts aged <55 and ≥55 yrs: median (95% CI) 14.3 mos (6.0–not estimable [NE]) vs 11.7 mos (6.6–NE), respectively. While in remission, 29.8% of pts aged <55 yrs and 2.4% aged ≥55 yrs proceeded to consolidative stem cell transplant (SCT). Incidence of Grade ≥3 cytokine release syndrome (CRS; 2.5% vs 2.1%) and immune effector cell-associated neurotoxicity syndrome (ICANS; 5.1% vs 10.4%) were low for pts aged <55 and ≥55 yrs, respectively. Treatment-related mortality within 3 mos post obe-cel infusion was 0% in pts aged <55 yrs vs 4.2% in pts aged ≥55 yrs. CAR T-cell persistence was similar in both age groups. Conclusions: Obe-cel treatment resulted in favorable ORR and EFS with low Grade ≥3 CRS/ICANS incidence in both age groups. These findings indicate that obe-cel is effective and has a positive benefit/risk profile regardless of age, including in older adults with R/R B-ALL despite few receiving consolidative SCT. Clinical trial information: NCT04404660 .
Source: Journal of Clinical Oncology
Institutions: Moffitt Cancer Center, King's College Hospital NHS Foundation Trust, The University of Texas MD Anderson Cancer Center, Universitat Autònoma de Barcelona, Vall d'Hebron Hospital Universitari, Manchester Royal Infirmary, Universitätsklinikum Würzburg, City Of Hope National Medical Center, University Hospitals Birmingham NHS Foundation Trust, Memorial Sloan Kettering Cancer Center, Newcastle upon Tyne Hospitals NHS Foundation Trust, University of California, San Francisco, Dana-Farber Cancer Institute, Autolus (United Kingdom), University College London
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4410808913