Comparison of obecabtagene autoleucel versus an external control arm in adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia

In the single-arm Phase Ib/II FELIX study (NCT04404660), obecabtagene autoleucel (obe-cel; CD19-directed autologous CAR T-cell therapy) demonstrated high overall remission rates (ORR) and a favorable safety profile in adults with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). To contextualize results from FELIX, we compared the efficacy and safety of obe-cel 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; secondary endpoints included overall survival (OS). Event-free survival (EFS) and safety were exploratory endpoints. Among the intent-to-treat population in FELIX (n = 107), obe-cel demonstrated significantly higher ORR than non-CAR T-cell therapies (67.3% vs 51.4%; odds ratio 1.9; p = 0.0257). Median OS was longer with obe-cel when censoring for hematopoietic stem cell transplant (15.1 vs 7.0 months; p = 0.0015) and without censoring (13.9 vs 7.8 months; p = 0.0430). EFS was significantly improved with obe-cel (median 9.8 vs 2.5 months; p < 0.0001). Safety profiles were comparable between groups, with similar rates of Grade ≥3 adverse events. Obe-cel offers superior remission rates and survival benefits over current SoC non-CAR T-cell therapies, with an acceptable safety profile; its use could address unmet needs in adult R/R B-ALL.