Comparative Analysis Shows ORR, OS Benefits With Obe-Cel in R/R B-ALL

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Obecabtagene autoleucel (obe-cel; Aucatzyl) was associated with a higher overall response rate (ORR) and prolonged overall survival (OS) compared with non–CAR T-cell therapies in adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), according to a data from comparative analysis, which included patients given the CAR T-cell therapy during the phase 1b/2 FELIX study (NCT04404660).

The prospective, non-interventional analysis utilized patient-level data from the FELIX trial and matched external control arms (ECAs) using a propensity score-based methodology. The objective was to contextualize efficacy and safety outcomes of obe-cel relative to standard non–CAR T-cell therapies across 2 populations: the modified treated (mITT) and intent-to-treat (ITT) groups.

Data presented at the 51st Annual EBMT Meeting demonstrated that in the mITT cohort, the ORR was 79.8% with obe-cel (n = 84) compared with 54.8% in the ECA group (n = 84), corresponding to a rate difference of 25.0% (95% CI, 9.4%-38.6%; odds ratio (OR), 3.3; 95% CI, 1.6-6.5; P = .0009). In the ITT population, the ORR was 67.3% with obe-cel (n = 107) vs 51.4% with ECA (n = 107), translating to a rate difference of 15.9% (95% CI, 2.3%-28.8%; OR, 1.9; 95% CI, 1.1–3.4; P = .0257).

OS analyses were performed both with and without censoring for subsequent hematopoietic stem cell transplant (HSCT). Without HSCT censoring, the median OS was 14.2 months with obe-cel vs 8.5 months with ECA in the mITT group (HR, 0.73; 95% CI, 0.47-1.13; P = .0606); these values were 13.9 vs 7.0 months, respectively, in the ITT group (HR, 0.70; 95% CI, 0.50-0.99; P = .0450).

When censored for HSCT, median OS was further prolonged with obe-cel at 15.5 vs 10.2 months in the mITT group (HR, 0.52; 95% CI, 0.32-0.82; P = .0046). The median OS was15.1 months for obe-cel vs 7.0 months for the ECA arm in the ITT group (HR, 0.53; 95% CI, 0.36-0.79; P = .0015).

"Treatment with obe-cel demonstrated higher ORR, longer OS, and [longer] event-free survival [EFS] vs non–CAR T-cell therapies in matched ECAs, along with a manageable safety profile. These data support a positive benefit-risk profile with obe-cel for the treatment of adult [patients with] relapsed/refractory B-ALL," Max S. Topp, MD, head of the Department of Hematology at University Hospital of Würzburg in Germany, said in his presentation.

Prospective Study Design

Patient-level data were drawn from the FELIX morphological disease cohort, including individuals with greater than 5% bone marrow blasts at screening. The mITT population included patients who received obe-cel during the FELIX study; the ITT population included patients who were enrolled on FELIX, irrespective of whether they received the CAR T-cell therapy.

The data cutoff for this cohort was February 7, 2024. Comparator data were sourced from global hematopoietic cell transplant (HCT) datasets within the Medidata Enterprise Data Store. All HCTs included in the analysis were initiated in 2014 or later, and data were limited to 5 or fewer contributing HCT studies.

The ECA arm included patients who received at least 1 dose of blinatumomab (Blincyto), standard chemotherapy, or inotuzumab ozogamicin (Besponsa). Investigators used a propensity score–based approach using the following factors to match the cohorts: age at enrollment, sex, ECOG performance status, bone marrow blast percentage, number of prior lines of therapy, extramedullary disease status, receipt of prior HSCT, and refractoriness to last line of therapy.

The primary end point of the analysis was ORR, and OS was a secondary end point. Exploratory end points included EFS and safety.

Baseline Patient Demographics

Baseline patient characteristics were assessed pre-matching for both the FELIX and ECA) populations in the mTT and ITT cohorts. In the FELIX mITT group (n = 94), the median age was 50.0 years (interquartile range [IQR], 33.0-62.0) compared with 36.0 years (IQR, 25.0-54.0) in the ECA mITT population (n = 415). In the FELIX ITT cohort (n = 112), the median age was 49.0 years (IQR, 33.5-62.5); in the ECA ITT group (n = 415), the median age was 36.0 years (IQR, 25.0-54.0). Across cohorts, 50.0% to 55.4% of patients were male.

The majority of patients in both FELIX cohorts had an ECOG performance status of 1 (mITT, 57.4%; ITT, 64.3%). Median baseline bone marrow blast percentages were 41.1% (IQR, 5.0%-87.0%) in the FELIX mITT group and 71.0% (IQR, 37.5%-86.3%) in the ECA group.

Regarding treatment history, approximately 31% of patients in the FELIX cohorts had received more than 2 prior lines of therapy, and over half were refractory to their last line (mITT, 54.3%; ITT, 52.7%). Extramedullary disease was reported in 20.2% (mITT) and 18.8% (ITT) of FELIX participants.

Prior allogeneic HSCT was documented in 36.3% of patients in the FELIX mITT group and 38.4% in the ITT cohort. Philadelphia chromosome–positive disease was reported in 26.6% (mITT) and 23.2% (ITT) of FELIX patients, compared with 3.9% in both ECA groups.

Additionally, prior treatment with blinatumomab was reported in 35.1% of the FELIX mITT cohort and 36.6% of the ITT population vs 0.7% in both ECA groups. Similarly, 45.7% and 33.0% of FELIX mITT and ITT patients, respectively, had prior exposure to inotuzumab ozogamicin, compared with 0.7% in the ECA cohorts.

Safety Analysis

Treatment-emergent adverse effects (TEAEs) were reported in all patients treated with obe-cel in the mITT population and 97.6% of patients in the ECA mITT population receiving non–CAR T-cell therapies. Grade 3 or higher TEAEs occurred in 81.0% of patients in the obe-cel group and 86.9% in the ECA group.

Cytokine release syndrome (CRS) of any grade occurred more frequently with obe-cel (76.2%) compared with ECA (26.2%); the incidence of grade 3 or higher CRS was 3.6% in both groups. Infections were reported in 51.2% of patients in the obe-cel cohort and 59.5% in the ECA group, with grade 3 or higher infections reported in 26.2% vs 28.6% of patients, respectively.

Nervous system or psychiatric disorders were observed in 59.5% of patients treated with obe-cel compared with 44.0% in the ECA arm; grade 3 or higher effects occurred in 10.7% and 9.5% of patients, respectively.

Notably, the proportion of patients who died within 3 months of treatment initiation was lower in the obe-cel arm (14.3%) compared with the ECA arm (19.0%).

Reference

Topp MS, Shah BD, Jabbour E, et al. Obecabtagene autoleucel (obe-cel) versus external control arm (ECA) matched comparisons in adult patients with relapsed/refractory B-cell acute lymphoblastic leukaemia (R/R B-ALL). Presented at: 51st Annual EBMT Meeting; March 30-April 2, 2025; Florence, Italy. Abstract OS13-03.