Dr Roddie on Outcomes With Obe-Cel by Disease Burden in R/R B-ALL

Our belief is that the use of…alternate agents, novel agents, targeted agents, rather than chemotherapy, is a more effective [bridging therapy strategy to take] what is effectively a high-risk patient with lots of disease [burden] at the point of screening and bring their risk right down to the level of a patient who presents to you at screening with morphologic remission.

Claire Roddie, PhD, FRCPath, MBChB, MRCP, an associate professor in hematology at the University College London, an honorary hemato-oncology/cell therapies consultant at University College London Hospitals, and clinical science director of CAR-T and Vector at the Centre for Cell, Gene and Tissue Therapeutics/Royal Free Hospital, discussed outcomes with obecabtagene autoleucel (obe-cel; Aucatzyl) based on disease burden at the time of screening and lymphodepletion (LD) in adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL).

At the 2026 EHA Congress, Roddie and colleagues presented data from an analysis of the phase 1b/2 FELIX trial (NCT04404660), looking at outcomes based on disease burden at the time of screening and LD.

Although Roddie noted that patients with higher disease burden can still achieve meaningful responses with obe-cel, findings demonstrated that at a median follow-up of 32.8 months (range, 19.9-52.8), the median event-free survival (EFS) was not reached in patients in morphologic remission at screening and/or LD, defined as less than 5% bone marrow blasts. Conversely, the median EFS was 9.0 months (95% CI, 5.1-12.3) in those with no morphologic remission at either time point.

Roddie highlighted that one of the most clinically relevant observations from this trial was the effect of bridging therapy. Among patients who presented at screening with high disease burden, a subset achieved morphologic remission before LD following bridging therapy. These patients experienced long-term remission rates and survival outcomes that closely mirrored those of patients who entered the study in morphologic remission, suggesting that effective bridging could mitigate the adverse prognostic effect of high baseline disease burden at the time of obe-cel infusion.

Importantly, baseline marrow blast percentage alone did not distinguish bridging responders from nonresponders. Instead, the type of bridging therapy appeared to be a defining factor, Roddie explained. Patients who did not experience a reduction in disease burden prior to LD most commonly received chemotherapy alone as bridging therapy, despite having chemotherapy-refractory disease, she explained. Conversely, patients who achieved morphologic remission before LD more frequently received novel approaches as bridging therapy, including immunotherapies, TKIs, and other targeted agents, she noted.

Roddie suggested that these findings support a shift away from chemotherapy-only bridging strategies in favor of novel-agent approaches capable of achieving meaningful cytoreduction before CAR T-cell therapy infusion. Lowering disease burden prior to LD may help improve both efficacy and safety outcomes with obe-cel, effectively moving high-risk patients into a prognostically favorable category before CAR T-cell therapy, she concluded.