European Commission Approves Obe-Cel for Adult R/R B-Cell Precursor Acute Lymphoblastic Leukemia

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The European Commission approved obecabtagene autoleucel (obe-cel; Aucatzyl) for the treatment of adult patients 26 years of age or older with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (B-ALL).1

The regulatory decision was supported by data from the phase 1/2 FELIX trial (NCT04404660), which showed that at a median follow-up of 20.3 months, patients in cohort 2A treated with the CAR T-cell therapy (n = 127) achieved an overall remission rate (ORR) of 77% (95% CI, 67%-85%), including a complete remission (CR) rate of 55% (95% CI, 45%-66%) and a CR with incomplete hematologic recovery (CRi) rate of 21% (95% CI, 14%-31%).2

At a median follow-up of 21.5 months, the median event-free survival (EFS) was 11.9 months (95% CI, 8.0-22.1), and patients experienced estimated 6- and 12-month EFS rates of 65.4% and 49.5%, respectively. The median overall survival (OS) was 15.6 months (95% CI, 12.9-not evaluable), with estimated 6- and 12-month OS rates of and 80.3% and 61.1%, respectively.

“We believe [obe-cel] represents an important new treatment option for physicians treating adult [patients with] relapsed/refractory B-ALL. With the European Union [EU] marketing authorization, we are now evaluating market entry opportunities in EU countries,” Christian Itin, PhD, chief executive officer of Autolus Therapeutics, stated in a news release.1

In November 2024, the FDA approved obe-cel for the treatment of adult patients with relapsed or refractory B-ALL.3 This regulatory decision was also supported by data from FELIX.

FELIX Overview

Cohort 2A of the study included patients with relapsed/refractory B-ALL who had morphologic disease at baseline, defined as a bone marrow blasts level of at least 5%.2

Enrolled patients underwent leukapheresis, and prior to lymphodepletion, bridging therapy was permitted, with the exception of blinatumomab (Blincyto). Lymphodepletion consisted of fludarabine at 30mg/m2 for 4 days and cyclophosphamide 500mg/m2 IV for 2 days prior to the administration of the first dose of obe-cel on day 1.

In patients with a bone marrow blasts level of more than 20% prior to lymphodepletion received the first dose of obe-cel at a dose of 10×106 CAR T cells, compared with 100×106 for those with a bone marrow blasts level of less than 20%. The second dose was given 9 days later, with a combined target total for both doses of 410×106 CAR T cells.

ORR served as the trial’s primary end point. Secondary end points comprised CR rate, duration of remission, EFS, minimal residual disease–negative remission, OS, progression-free survival, relapse-free survival, safety, stem-cell transplantation, and ORR without stem-cell transplantation or other subsequent therapies.

Regarding safety, any-grade cytokine release syndrome (CRS) occurred at a rate of 68.5%, including a grade 3 or higher rate of 2.4%. The median time to onset of CRS was 8 days (range, 1-23), with a median duration of 5 days (range, 1-21). Immune effector cell–associated neurotoxicity syndrome (ICAN) was reported in 22.8% of patients, including grade 3 or higher ICANS in 7.1% of patients. The median time to onset of ICANS was 12 days (range, 1-31), with a median duration of 8 days (range, 1-53).

Febrile neutropenia occurred in 24.4% in the 60 days following the infusion of obe-cel. Five deaths due to infections were reported, including 2 due neutropenic sepsis, 2 from sepsis, and one from abdominal infection. Only 1 of the neutropenic sepsis deaths was considered related to the CAR T-cell therapy. Two deaths overall were attributed to obe-cel: 1 patient died due to acute respiratory distress syndrome with ongoing ICANS, and the other from neutropenic sepsis.

References

1. Autolus Therapeutics’ CAR T therapy Aucatzyl (obecabtagene autoleucel) granted European marketing authorization for adult patients (age 26 and older) with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (R/R B-ALL). News release. Autolus Therapeutics. July 21, 2025. Accessed July 21, 2025. https://autolus.gcs-web.com/news-releases/news-release-details/autolus-therapeutics-car-t-therapy-aucatzylr-obecabtagene
2. Roddie C, Sandhu KS, Tholouli E, et al. Obecabtagene autoleucel in adults with B-cell acute lymphoblastic leukemia. N Engl J Med. 2024;391(23):2219-2230. doi:10.1056/NEJMoa2406526
3. FDA approves obecabtagene autoleucel for adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia. FDA. November 8, 2024. Accessed July 21, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-obecabtagene-autoleucel-adults-relapsed-or-refractory-b-cell-precursor-acute