Dr Muffly on the Role of Obe-Cel in R/R B-Cell Precursor ALL

“The [FDA] approval of obe-cel on the heels of the FELIX trial results provides what is now our third CAR T-cell therapy for patients with relapsed/refractory, B-ALL.”

Lori Muffly, MD, MS, associate professor of medicine, Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford Medicine, discusses where obecabtagene autoleucel (obe-cel; Aucatzyl) fits into the the treatment paradigm for patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (B-ALL).

On November 8, 2024, the FDA approved obe-cel for the treatment of adult patients with relapsed or refractory B-cell precursor ALL. Data from the study later published in the New England Journal of Medicine demonstrated that patients enrolled in cohort 2A with morphologic disease at baseline who received at least 1 infusion of obe-cel (n = 97) achieved an overall remission rate (ORR) of 77% (95% CI, 67%-85%); the complete remission (CR) and CR with incomplete hematologic recovery (CRi) rates were 55% (95% CI, 45%-66%) and 21% (95% CI, 14%-31%), respectively.

Muffly explains that obe-cel represents the third CAR T-cell therapy approved within the ALL treatment paradigm, joining tisagenlecleucel (tisa-cel; Kymriah) and brexucabtagene autoleucel (brexu-cel; Tecartus). Obe-cel expands treatment options for adult patients, providing an additional CD19-directed autologous CAR T-cell therapy with distinct mechanistic properties, she notes. These different CAR T-cell therapies have different features and characteristics, and although there are pros and cons with each product, having another treatment option is ultimately a win for patients, she explains.

Obe-cel utilizes a unique binder compared with tisa-cel and brexu-cel, Muffly continues. The rapid off-rate of obe-cel is designed to minimize prolonged antigen engagement that can lead to CAR T-cell overstimulation and exhaustion, she says, adding that this feature may enhance T-cell persistence, potentially improving long-term therapeutic efficacy.

Muffly emphasizes that the approval of obe-cel provides another therapeutic option for adults with relapsed/refractory B-cell precursor ALL, enabling clinicians to tailor treatment selection based on patient-specific factors.