Dr Bishop on the Utility of Obe-Cel in Relapsed/Refractory B-ALL

Michael R. Bishop, MD, professor, medicine, director, Hematopoietic Stem Cell Transplantation Program, Hematology and Oncology (Cancer) Immunotherapy, University of Chicago Medicine, discusses outcomes from a pooled analysis of the ongoing phase 1b/2 FELIX study (NCT04404660), highlighting the safety of the investigational agent obecabtagene autoleucel (obe-cel; AUTO1) in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL).

Findings from the analysis were presented at the 2023 ASH Annual Meeting, revealing that obe-cel treatment elicited lasting responses in patients regardless of their leukemic burden during lymphodepletion. Furthermore, in January 2024, the FDA commenced review of a biologics license application aiming to secure approval for obe-cel for the treatment of adult patients with relapsed/refractory B-ALL. The regulatory acceptance of this application stemmed from results observed in the FELIX trial.

The outcomes from the pooled analysis served as an update to the findings initially published in the Journal of Clinical Oncology by lead study author Claire Roddie, MD, associate professor of haemato-oncology at University College London, and coauthors, Bishop begins. Investigatorsthen shared updated results from FELIX at the 2023 ASCO Annual Meeting. The findings from the pooled analysis that were subsequently presented at the 2023 ASH Annual Meeting clarifiedthe outcomes initially observed across patient cohorts, he explains, adding that a key focus of the pooled analysis was on assessing disease burden among patients receiving cell therapy.

Prior to CAR T-cell therapy, patients receive lymphodepleting chemotherapy, aimed at reducing disease burden and creating immune space, Bishop expands. The pooled analysis dissected these aspects and analyzed the adverse effect profiles experienced among different patient groups, he states. Notably, the safety profile of obe-cel emerged as a crucial aspect of the study, Bishop says.

Obe-cel features a distinct receptor compared with those in most other CAR T-cell therapies used in non-Hodgkin lymphoma and B-ALL, he continues. Although this unique receptor targets the CD19 protein like other CAR T-cell therapies, it also exhibits a rapid on and off mechanism, mimicking the biological processes of physiological T-cell receptors, Bishop states. This characteristic is believed to mitigate toxicity, he notes. In the overall patient population in FELIX, the incidence of grade 3 or higher cytokine release syndrome was 2%, and the incidence of grade 3 or higher immune effector cell–associated neurotoxicity syndrome was 7%. These safety data stand in stark contrast to those typically observed with other CAR T-cell products targeting CD19, particularly in ALL, he concludes.