Dr Logan on Obe-Cel as a Potential Definitive Treatment in R/R B-ALL

"We haven't figured out how to identify patients who are likely to be cured with obe-cel as definitive therapy in relapsed B-ALL. [However], we know that patients who had Ph-positive ALL tend to do better. Post allo-HCT would be another setting where we might favor obe-cel as definitive therapy, and the other setting where we see it do really well is in patients who have very low disease burden."

Aaron C. Logan, MD, PhD, associate professor of Clinical Medicine in the Division of Hematology/Oncology and director of the Hematologic Malignancies Tissue Bank at the University of California, San Francisco (UCSF), discussed the potential role of obecabtagene autoleucel (obe-cel; Aucatzyl) as definitive therapy for adult patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL), without the need for consolidative allogeneic hematopoietic stem cell transplant (allo-HCT).

Findings from an analysis of the phase 1b/2 FELIX trial (NCT04404660) presented at the 2025 EHA Congress showed that prolonged obe-cel persistence, a lower bone marrow blasts percentage, and administration of obe-cel earlier in the treatment course were independently associated with extended event-free survival. These data suggest that obe-cel may function as a curative therapy in select patient populations, particularly when delivered under favorable clinical conditions.

Logan noted that although definitive predictors of long-term remission post–obe-cel remain to be identified, several patterns emerged in the analysis. Patients with Philadelphia chromosome (Ph)–positive B-ALL tended to derive higher rates of complete response (CR)/CR with incomplete hematologic recovery (CRi) from obe-cel, potentially due to distinct underlying disease biology. In this setting, consolidation with a TKI following CAR T-cell therapy is often pursued, further supporting a non-transplant, TKI-maintenance strategy, he added.

Logan also highlighted findings from FELIX indicating that patients who relapsed following a prior transplant appeared to achieve higher rates of CR/CRi than those without prior allo-HCT, suggesting that CAR T cells generated from post-transplant immune cells may possess enhanced antileukemic activity. Although this same outcome was not observed in the phase 1/2 ZUMA-3 trial (NCT02614066) evaluating brexucabtagene autoleucel (brexu-cel; Tecartus), real-world evidence has shown a benefit in patients who received CAR T cells post–allo-HCT vs those who had not previously received allo-HCT, Logan noted.

Obe-cel as definitive therapy could also provide benefit for patients with minimal residual disease (MRD)–positive or low disease burden (<5%) prior to CAR T-cell infusion, Logan continued. Administration of obe-cel in the setting of early relapse or MRD progression—rather than in fulminant relapse—may be optimal for achieving long-term remission without subsequent allo-HCT, he concluded.