Dr Logan on the Integration of Obe-Cel into Relapsed/Refractory ALL Management

“[The safety profile of obe-cel] changes the barriers to proceed to CAR T-cell [therapy] because we are less concerned about toxicity than we are with brexu-cel, so we may use CAR T cell [therapy] earlier in some patients.”

Aaron C. Logan, MD, PhD, a professor of clinical medicine at the University of California, San Francisco, discussed the significance of the FDA approval of the CAR T-cell therapy obecabtagene autoleucel (obe-cel; Aucatzyl) for patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (ALL).

In November 2024, the FDA approved obe-cel

 for the treatment of patients with relapsed/refractory B-cell precursor ALL. The approval was supported by data from the phase 1/2 FELIX trial (NCT04404660), which demonstrated that efficacy-evaluable patients (n = 65) achieved a complete remission (CR) within 3 months of therapy at a rate of 42% (95% CI, 29%-54%). Among patients who responded within 3 months, the median duration of CR was 14.1 months (95% CI, 6.1-not reached).

Obe-cel is unique among CAR T-cell therapies due to a reduced toxicity profile compared with other agents in its class, such as brexucabtagene autoleucel (brexu-cel; Tecartus), Logan began. This is likely due to its target, he said; although obe-cel and brexu-cel are both directed toward CD19, brexu-cel utilizes a CD28 costimulatory domain and a high-affinity FMC63-derived single-chain variable fragment (scFv), and obe-cel has a 4-1BB costimulatory domain and a modified scFv. The mechanism of action of obe-cel leads to a heightened physiologic reaction between the CAR T cells and the leukemia cells, potentially reducing immunologic toxicities such as cytokine release syndrome (CRS), he explained.

Moreover, obe-cel is administered by split dosing, which also contributes to its favorable toxicity profile, Logan said. The agent produces low rates of CRS and neurotoxicity, he added. At the time of obe-cel’s approval, data from FELIX showed that the rate of grade 3 CRS was 3% and the rate of grade 3 or higher neurologic toxicity was 12%.

This safety profile changes the barrier to entry for patients to receive CAR T-cell therapy, allowing obe-cel to potentially be used in earlier lines of therapy, including those who are not good candidates for brexu-cel because of its toxicity profile, Logan said. The FDA approval should lead to increased uptake of CAR T-cell therapy for the treatment of patients with B-cell ALL, Logan concluded.

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Aaron C. Logan, MD, PhD, discusses the FDA approval of the obe-cel in relapsed/refractory B-cell precursor acute lymphoblastic leukemia.

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.

Aaron C. Logan, MD, PhD, discusses the potential use of obe-cel as definitive treatment in adult relapsed/refractory B-ALL.
 

Aaron C. Logan, MD, PhD, University of California San Francisco

Articles

Dr Logan on the Integration of Obe-Cel into Relapsed/Refractory ALL Management

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