Dr Logan on the Integration of Obe-Cel into Relapsed/Refractory ALL Management

“[The safety profile of obe-cel] changes the barriers to proceed to CAR T-cell [therapy] because we are less concerned about toxicity than we are with brexu-cel, so we may use CAR T cell [therapy] earlier in some patients.”

Aaron C. Logan, MD, PhD, a professor of clinical medicine at the University of California, San Francisco, discussed the significance of the FDA approval of the CAR T-cell therapy obecabtagene autoleucel (obe-cel; Aucatzyl) for patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (ALL).

In November 2024, the FDA approved obe-cel for the treatment of patients with relapsed/refractory B-cell precursor ALL. The approval was supported by data from the phase 1/2 FELIX trial (NCT04404660), which demonstrated that efficacy-evaluable patients (n = 65) achieved a complete remission (CR) within 3 months of therapy at a rate of 42% (95% CI, 29%-54%). Among patients who responded within 3 months, the median duration of CR was 14.1 months (95% CI, 6.1-not reached).

Obe-cel is unique among CAR T-cell therapies due to a reduced toxicity profile compared with other agents in its class, such as brexucabtagene autoleucel (brexu-cel; Tecartus), Logan began. This is likely due to its target, he said; although obe-cel and brexu-cel are both directed toward CD19, brexu-cel utilizes a CD28 costimulatory domain and a high-affinity FMC63-derived single-chain variable fragment (scFv), and obe-cel has a 4-1BB costimulatory domain and a modified scFv. The mechanism of action of obe-cel leads to a heightened physiologic reaction between the CAR T cells and the leukemia cells, potentially reducing immunologic toxicities such as cytokine release syndrome (CRS), he explained.

Moreover, obe-cel is administered by split dosing, which also contributes to its favorable toxicity profile, Logan said. The agent produces low rates of CRS and neurotoxicity, he added. At the time of obe-cel’s approval, data from FELIX showed that the rate of grade 3 CRS was 3% and the rate of grade 3 or higher neurologic toxicity was 12%.

This safety profile changes the barrier to entry for patients to receive CAR T-cell therapy, allowing obe-cel to potentially be used in earlier lines of therapy, including those who are not good candidates for brexu-cel because of its toxicity profile, Logan said. The FDA approval should lead to increased uptake of CAR T-cell therapy for the treatment of patients with B-cell ALL, Logan concluded.