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).

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 .