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FDA grants approval to obecabtagene autoleucel for relapsed/refractory adult B-cell acute lymphoblastic leukemia

On November 8, 2024, the U.S. Food and Drug Administration (FDA) granted the approval of obecabtagene autoleucel (obe-cel) for adult patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL).1

Obe-cel is an autologous CD19-directed CAR T-cell therapy with a unique design featuring a fast target-binding off-rate, which minimizes excessive T-cell activation, thereby reducing toxicity and T-cell exhaustion. This mechanism may contribute to enhanced rates of durable remission in patients with R/R B-ALL.2 

The approval was supported by data from the pivotal Phase Ib/II open-label, multi-center, single-arm FELIX trial (NCT04404660), which enrolled over 100 adult patients with R/R B-ALL across academic and non-academic centers in the United States, United Kingdom, and Europe.2 Key eligibility criteria included relapse after a remission duration of 12 months or less, two or more prior lines of systemic treatment, or R/R disease at least three months post-allogeneic stem cell transplantation (SCT).1

In this trial, the primary efficacy endpoints were the rate and duration of complete remission (CR) within three months post-infusion. Of the 65 evaluable patients, 42% (95% CI: 29%-54%) achieved CR within three months, with a median CR duration of 14.1 months (95% CI: 6.1 months, not reached).1 After a median follow-up of 16.6 months, the overall CR or CR with incomplete blood count recovery rate was 78% among infused patients. Among those who responded, 17% proceeded to consolidative SCT while in remission, achieving a 100% rate of measurable residual disease (MRD) negativity. The 12-month overall survival (OS) rate was 61% with censoring for SCT and 59% without censoring.3

In terms of safety, cytokine release syndrome (CRS) was observed in 75% of patients, with grade 3 severity in 3%. Neurologic adverse events (AEs) occurred in 64% of patients, with 12% experiencing grade ≥3 toxicities, including immune effector cell-associated neurotoxicity syndrome (ICANS) in 24% (grade ≥3 in 7%). Common non-laboratory AEs (occurrence ≥20%) included CRS, unspecified infections, musculoskeletal pain, viral infections, fever, nausea, bacterial infections, diarrhea, febrile neutropenia, ICANS, hypotension, pain, fatigue, headache, encephalopathy, and hemorrhage.1

We spoke with Elias Jabbour, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, at the 65th ASH Annual Meeting and Exposition, who discussed obe-cel and the FELIX trial. Dr Jabbour highlighted, “Today, when you relapse (with) ALL, it is a death sentence. We have immune therapies with short-lived responses…The problem with these CAR T-cells is toxicities, high cytokine release syndrome rate, as well as neurotoxicities. So the good thing about the obe-cel is what is called the fast-off CAR-Ts, limiting the binding of the CAR-T and therefore we don’t have the storm of the T-cells, but we have durable T-cells.”

The approval of obe-cel introduces a promising new treatment option for adults with R/R B-ALL, offering potentially improved safety and efficacy compared with existing CAR T-cell therapies. Its unique engineering provides the potential for longer-lasting remissions with a lower risk of severe AEs. With robust efficacy demonstrated in the FELIX trial, obe-cel has the potential to enhance treatment outcomes and provide hope for patients facing limited options in managing this aggressive leukemia.

References

  1. U.S. Food and Drug Administration. FDA approves obecabtagene autoleucel for adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia. Available here. (Last accessed 30/10/2024).
  2. Autolus. Autolus Therapeutics announces acceptance of Biologics License Application for obecabtagene autoleucel (obe-cel) as a potential treatment for relapsed/refractory Adult B-cell Acute Lymphoblastic Leukemia (ALL). Available here. (Last accessed 30/10/2024).
  3. Jabbour E, Tholouli E, Sandhu KS, et al. Obecabtagene autoleucel (obe-cel, AUTO1) in adults with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL): Overall survival (OS), event-free survival (EFS) and the potential impact of chimeric antigen receptor (CAR)-T cell persistency and consolidative stem cell transplantation (SCT) in the open-label, single-arm FELIX phase Ib/II study. Journal of Clinical Oncology. 2024 May;42(16_suppl):65.

Written by Hannah Elkheir

Edited by Anya Dragojlovic Kerkache