New CAR-T Drug Induces Durable Remissions in ALL, Published Data Show

Use of the anti-CD19 CAR T-cell therapy obecabtagene autoleucel (obe-cel; Aucatzyl) resulted in durable remissions among patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL), according to results from the phase Ib/II FELIX trial.

In a cohort of 94 patients with morphologic disease, overall remission occurred in 77% of those who received at least one infusion of obe-cel, with complete remission (CR) in 55% and CR with incomplete hematologic recovery in 21%, meeting the trial’s primary endpoint, reported Claire Roddie, MD, of the University College London Cancer Institute, and colleagues in the New England Journal of Medicine.

In the full study population of 127 patients who received at least one obe-cel infusion, 99 achieved a CR or CR with incomplete hematologic recovery. The median event-free survival (EFS) was 11.9 months, and the estimated 6- and 12-month EFS rates were 65.4% and 49.5%, respectively. The median overall survival (OS) was 15.6 months, and the estimated 6- and 12-month OS rates were 80.3% and 61.1%, respectively.

“Irrespective of disease status, a majority of patients achieve complete response, even in very high-risk groups,” Roddie told MedPage Today. “Despite a large proportion of patients with significant disease burden pre-CAR, we saw very little high-grade immunotoxicity, meaning that this CAR can be safely delivered to patients who might otherwise not be considered fit enough for CAR.”

Obe-cel’s recent FDA approval was supported by results from this trial, showing that 42% of 65 patients achieved a CR within 3 months. Overall, 63% of participants achieved a CR during the study, including 12% with CR and incomplete hematologic recovery.

Roddie and colleagues reported that a high incidence of overall remission was observed across all patient subgroups after obe-cel infusion, but a lower incidence was seen in patients with a high bone marrow burden (>75% bone marrow blasts) compared with those with an intermediate bone marrow burden (5% to 75% bone marrow blasts) before lymphodepletion (65% vs 82%).

They also found that bone marrow burden before lymphodepletion correlated with EFS and OS. Patients with low (

This suggests “that low-to-intermediate bone marrow burden is optimal for CAR T-cell efficacy and toxicity and that optimized bridging therapy approaches toward better tumor clearance before CAR T-cell therapy may improve outcomes,” Roddie and colleagues wrote.

Obe-cel was associated with a low incidence of severe immune-related toxic effects. Specifically, cytokine release syndrome developed in 87 (68.5%) of the 127 patients, but was grade ≥3 in only three patients. Immune effector cell-associated neurotoxicity syndrome (ICANS) developed in 22.8% of patients, with events of grade 3 or higher in nine patients.

Moreover, severe ICANS after obe-cel infusion was largely limited to patients with a high bone marrow burden before lymphodepletion, “which suggests that obe-cel may be safely administered in an ambulatory setting in patients with a low bone marrow burden,” Roddie and colleagues noted.

The FELIX study was conducted at 34 sites in Spain, the U.K., and the U.S., and had phase Ib (16 patients who received at least one infusion of obe-cel) and phase II components (111 patients, including the 94 with morphologic disease). Median age was 47, 52% were men, and 74% were white.

Participants had received a median of two previous lines of therapy, and 52% were refractory to their last line of therapy. Overall, 41.7% of patients had previously received blinatumomab (Blincyto), 31.5% had received inotuzumab ozogamicin (Besponsa), and 16.5% had received both; 44.1% of patients had previously undergone allogeneic stem cell transplantation.

The median percentage of bone marrow blasts was 40%, with

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