More than a third of patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) treated with the CAR T-cell therapy obecabtagene autoleucel (obe-cel) remained in remission at a follow-up of 3 years, without the need for additional interventions, new research showed.

“At a median follow-up of approximately 3 years, there is a sustained benefit for duration of response, event-free survival (EFS), and overall survival (OS)” said senior author Elias Jabbour, MD, of the MD Anderson Cancer Center, in Houston, in research presented last week at the Society of Hematologic Oncology (SOHO) 2025.

Importantly, “these results suggest that a proportion of patients may not need further therapy,” he said, noting that “longer follow-up, further analyses, and independent validation are needed to confirm results.”

Obe-cel, an autologous CD19-directed CAR T-cell therapy, was approved for the treatment of adult R/R B-ALL in November 2024, based on the results of the FELIX phase 1b/2 clinical trial, in which as many as 77% of patients with the disease achieved remission at a median follow-up of 20.3 months.

In the most recent update, at a median of 21.5 months, 40% of responders to obe-cel had maintained remission without the need for consolidative stem cell therapy or other anti-cancer therapies, with the exception of TKIs.

The current update presented by Jabbour included data on 127 patients from the FELIX trial at a median follow-up of 3 years, including efficacy outcomes and a post hoc analysis of clinical factors that were predictive of long-term outcomes.

After adjustment for key confounders in a multivariate analysis, the study showed that with a median follow-up of 32.8 months, the rate of remission among initial responders without subsequent stem cell transplantation or other therapy was 38.4% (38 patients).

While in remission, 18.2% of patients did go on to receive subsequent stem cell transplantation at the median 21.5-month follow-up, with no further cases reported at the 32.8-month follow-up.

Other factors that remained unchanged since the 21-month follow-up included the rate of starting new anti-cancer therapy, which was 5.1%, and the rate of relapse, which was 31.3%.

While five patients (5.1%) in the study died while in remission without subsequent therapy at 21.5 months, there were two additional deaths, related to infections, by 32.8 months while patients were in remission.

The median duration of response was 42.5 months; the rate of EFS at 2 years, censoring for consolidative stem cell transplant was 43%, and OS, without censoring for stem cell transplant, was approximately 46%.

In terms of safety, no cases of cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) were reported in the latest follow-up, with four infections and two malignancies, which were not related to obe-cel.

“No significant safety concerns were observed,” Jabbour said.

CRS and ICANS are known to be common with CAR T therapies, however, obe-cel is designed with a unique fast target binding off-rate that reduces excessive activation of programmed T cells, reducing toxicity and T-cell exhaustion, while improving CAR T-cell persistence, according to obe-cel developer Autolus Therapeutics.

Predictors of Response, Survival

In further analysis of the FELIX trial, key factors that were found to be independently associated with the achievement of a complete response (CR) or CR with incomplete hematologic recovery included being Philadelphia chromosome-positive vs negative (odds ratio [OR], 6.0), having had ≤ 3 prior lines of therapy vs > 3 prior lines (OR, 3.8), and < 5% vs > 75% bone marrow blasts at lymphodepletion (OR, 3.2).

In addition, having < 5% vs > 75% bone marrow blasts significantly correlated with EFS (hazard ratio [HR], 0.3) as well as OS (HR, 0.3), as was ongoing vs the loss of CAR T persistence (EFS: HR, 0.41; OS: HR, 0.50).

Having prior vs no prior allogeneic stem cell transplantation was also significantly associated with better EFS.

“Overall, we found that Ph-positive disease, earlier obe-cel use, and less refractory disease correlated with achieving higher remission rates,” Jabbour said.

“Lower disease burden at lymphodepletion and ongoing CAR T-cell persistence were independent factors associated with long-term remission and survival.”

“These data reinforce that obe-cel persistence is important for long-term survival without additional treatments, suggesting the potential of obe-cel as a definitive treatment,” the authors added.

This study was sponsored by Autolus Therapeutics PLC. Jabbour disclosed ties with Pfizer, Takeda, Amgen, AbbVie, Bristol Myers Squibb, Adaptive Biotechnologies, Genentech, Autolus Therapeutics, Ascentage Pharma, Taiho Pharmaceutical, Novartis, TargetRX, and Terns Pharmaceuticals.