Comparison of obecabtagene autoleucel versus an external control arm in adult patients with relapsed or refractory B-cell ALL

Obecabtagene autoleucel (obe-cel) is a CD19-directed autologous CAR T-cell therapy. In the single-arm phase 1b-2 FELIX study, obe-cel demonstrated high overall remission rates (ORR) and a favorable safety profile in adults with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). Efficacy and safety of obe-cel has now been compared with matched external control arms (ECA) derived from historical trials, using propensity score matching. ECAs represented standard of care (SoC) non-CAR T-cell therapies: blinatumomab, inotuzumab ozogamicin, and conventional chemotherapy. The primary endpoint was ORR. Among the intent-to-treat population in FELIX (n=107) obe-cell demonstrated significantly higher ORR than non-CAR T-cell therapies (67.3% versus 51.4%; OR 1.9; p=0.0257). Median overall survival was longer with obe-cel when censoring for hematopoietic stem cell transplant (15.1 versus 7.0 months; p=0.0015) and without censoring (13.9 versus 7.8 months; p=0.0430). Event-free survival was significantly improved with obe-cel (median 9.8 versus 2.5 months; p<0.0001). Safety profiles were comparable between groups, with similar rates of grade ≥ 3 adverse events. The authors conclude that obe-cel offers superior remission rates and survival benefits over current SoC non-CAR T-cell therapies, with an acceptable safety profile.