FELIX Analysis Suggests Consolidative SCT After Obe-Cel Does Not Improve EFS/OS in R/R B-ALL

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Consolidative stem cell transplant (SCT) after obecabtagene autoleucel (obe-cel; Aucatzyl) does not appear to have improved event-free survival (EFS) or overall survival (OS) in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), according to data from an analysis of the phase 1b/2 FELIX trial (NCT04404660) presented during the 51st Annual EBMT Meeting.1

At a median follow-up of 21.5 months (range, 8.6-41.4), and with a data cutoff date of February 7, 2024, 49% of responding patients (n = 99) who did not undergo consolidative SCT (n = 81) or received any other therapy after obe-cel infusion, are in remission vs 28% of those who did undergo SCT (n = 18).

When censoring for SCT (n = 127), the median EFS in those who received consolidative SCT was 11.9 months (95% CI, 8.0-22.1) with a 12-month EFS rate of 49.5% (95% CI, 39.6%-58.6%). The median OS was 23.8 months (95% CI, 12.9-not evaluable [NE]) with a 12-month OS rate of 63.7% (95% CI, 53.7%-72.0%). Without sensoring for SCT (n = 127), the median EFS was 9.0 months (95% CI, 6.6-14.3) with a 12-month EFS rate of 44.0% (95% CI, 35.2%-52.5%). The median OS was 15.6 months (95% CI, 12.9-NE) with a 12-month OS rate of 61.1% (95% CI, 52.0%-69.0%).

“These findings from the FELIX study suggest that in a large subgroup of patients, consolidative SCT may not be required following obe-cel treatment,” Karamjeet S. Sandhu, MD, of City of Hope National Medical Center, in Duarte, California, said in a presentation of the data.

What Came Before: Diving Into the FELIX Trial and Beyond

The open-label, multicenter, single-arm FELIX trial enrolled patients at least 18 years of age or older with relapsed or refractory B-ALL.2 Patients had refractory disease, with first relapse following a remission lasting for at least 1 year, relapsed or refractory disease following at least 2 lines of systemic therapy, or relapsed or refractory disease at least longer than 3 months after allogeneic SCT with a disease burden of at least 5% blasts in the bone marrow at the time of screening. Those with isolated extramedullary disease, active or serious infections that needed systemic antimicrobial treatment, active graft-vs-host disease, or a history or presence of central nervous system disorders, were excluded.

After screening, patients underwent leukapheresis and lymphodepletion comprised of 30 mg/m2 of fludarabine plus 500 mg/m2 of cyclophosphamide.1 They then received tumor burden–guided dosing. Those with bone marrow blasts of 20% or higher received obe-cel at 100 x 106 CAR T cells on day 1 (dose 1) and 310 x 106 CAR T cells on day 10 (dose 2). Those with bone marrow blasts higher than 20% received obe-cel at 10 x 106 CAR T cells (dose 1) and 400 x 106 CAR T cells (dose level 2). The target dose was always 410 x 106 CAR T cells.

The major efficacy measures of the study were rate and duration of complete remission (CR) within 3 months of obe-cel infusion.2 Investigators also examined rate and duration of overall CR. Earlier data from the study showed that the CR rate within 3 months of infusion with obe-cel in all efficacy-evaluable patients (n = 65) was 42% (95% CI, 29%-54%) and the median duration was 14.1 months (95% CI, 6.1-not reached [NR]). The overall CR rate at any time was 63% (95% CI, 50%-75%) and the median duration was 14.1 months (95% CI, 6.2-NR). These data led to the FDA’s decision to approve obe-cel in November 2024.3

A Closer Look at the Current Analysis

For the current analysis, the key study end points of interest were EFS and OS.1 Investigators sought to examine patient baseline characteristics and clinical outcomes in participants categorized by consolidative SCT status.

“In relapsed/refractory B-ALL, consolidative SCT is often required to improve clinical outcomes,” Sandhu said. “Consolidative SCT requires significant healthcare resources and is associated with potentially severe treatment-related toxicity and non-relapse mortality. CAR T-cell treatments capable of minimizing the requirement for consolidative SCT are needed.”

Among responders, the median patient age in those who received consolidative SCT vs those who did not was 35.5 years (range, 21-55) and 55.0 years (range, 20-81). Baseline characteristics for responders in the two groups were generally comparable with a few exceptions. In terms of ethnicity, 50% of those who underwent SCT were Hispanic or Latino vs 20% of those who did not. More patients who had SCT previously received blinatumomab (Blincyto) or inotuzumab ozogamicin (Besponsa) vs those who did not (78% vs 43%) and fewer patients had previously undergone allogeneic SCT (33% vs 51%).

When looking at disease characteristics and minimal residual disease (MRD) status in responders, it was found that fewer patients who underwent consolidative SCT had Philadelphia chromosome–positive disease than those who did not (11% vs 38%). Moreover, within those who had consolidative SCT, the percentages of bone marrow blasts at screening and lymphodepletion was 32% (95% CI, 0%-97%) and 35% (95% CI, 0%-95%); in those who did not have SCT, these respective rates were 40% (95% CI, 0%-100%) and 30% (95% CI, 0%-100%). In those who had SCT, 33% of patients had extramedullary disease at the time of screening and 22% had it at the time of lymphodepletion; these respective rates in those who did not have SCT was 16% and 15%. Seventy-eight percent of patients in both groups had best MRD results of less than 10-6 leukemic cells post–obe-cel infusion.

Of the 18 patients who received consolidative SCT, 17% experienced relapse only and 22% died following relapse. Death in remission was because of an adverse effect (AE) for 28% of patients or underlying cancer for 6% of patients. Of the 81 patients who did not receive consolidative SCT, 9% experienced relapse only and 30% died following relapse. Death in remission was due to an AE for 6% of patients. Six percent patients in this group started a new anticancer therapy.

“Lower disease burden at lymphodepletion was associated with improved EFS in patients who did not undergo consolidative SCT,” Sandhu noted.

Disclosures: Dr Sandhu disclosed receipt of research funding from Autolus Therapeutics.

References

1. Park JH, Jabbour E, Shah BD, et al. Outcomes of patients with relapsed/refractory B-cell acute lymphoblastic leukaemia (R/R B-ALL) treated with obecabtagene autoleucel (obe-cel) with or without consolidative allogeneic stem cell transplant. Presented at: 51st Annual EBMT Meeting; March 30-April 2, 2025; Florence, Italy. Abstract OS13-06.
2. Aucatzyl. Prescribing information. Autolus Inc; November 2024. Accessed April 4, 2025. https://www.fda.gov/media/183463/download
3. FDA approves obecabtagene autoleucel for adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia. FDA. November 8, 2024. Accessed April 4, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-obecabtagene-autoleucel-adults-relapsed-or-refractory-b-cell-precursor-acute