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

作者：Max S. Topp, Bijal Shah, Elias Jabbour, Jae H. Park, Paul Shaughnessy, Aaron C. Logan, Karamjeet S. Sandhu, Mehrdad Abedi, Michael R. Bishop, Daniel J. DeAngelo, Xiang Yin, Ruthanna Davi, Katharine Hodby, Ram Malladi, Wolfram Brugger, Justin Shang, Claire Roddie, Hagop M. Kantarjian · 发表于：Leukemia · 年份：2026 · DOI：10.1038/s41375-026-03045-7 · 研究领域：CAR-T cell therapy research、Acute Lymphoblastic Leukemia research、Virus-based gene therapy research

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.