ZUMA-3 Underscores Durable Survival Gains with Brexu-Cel in Relapsed B-Cell ALL

Relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) patients experienced a clear benefit in their overall survival rate when treated with brexucabtagene autoleucel (brexu-cel), according to new results from the ZUMA-3 study. These data was presented at the EHA 2025 Congress, with the study being led by Olalekan Oluwole, MD of the Vanderbilt-Ingram Cancer Center.

Brexu-cel is an autologous anti-CD19 CAR T-cell therapy approved for patients with R/R B-ALL who are over 18 in the United States and over 26 in the European Union based on the high complete remission (CR) or CR with incomplete hematologic recovery (CRi) rate observed in the phase 2 ZUMA-3 study. The research presented by Dr. Oluwole and his colleagues reported updated 5-year survival rates, safety, and causes of mortality in the patients of the ZUMA-3 study, including outcomes in key subgroups.

The primary endpoint of the study was the overall CR/CRi rate, with key secondary endpoints being Objective Survival (OS) rates and safety. Eligible R/R B-ALL patients underwent leukapheresis, optional bridging therapy, and lymphodepleting chemotherapy, followed by one infusion of brexu-cel (1×10⁶ CAR T cells/kg).

The 4-year OS rate among the 78 phase 1 & 2 patients was 40%, with survival benefits being observed across key subgroups. The median follow-up time of the study was 65.7 months, with responders (CR/CRi; n=57) reaching a median OS of 60.4 months, and those with a CR (n=47) not yet reaching a median OS.

The 5-year OS rates for patients with (n=38) and without (n=40) prior blinatumomab were 25% and 54%; patients with (n=17) and without (n=61) prior inotuzumab were 21% and 45%; and patients (n=29) and without (n=49) prior allogeneic stem cell transplantation (alloSCT) the rates were 36% and 42%, respectively. The 5-year OS rates were 42% (16.4-65.4) and 52% (35.8-66.5) overall.

One new adverse event and death, both in the same patient, occurred within the 4-year analysis: cervical cancer and death due to pulmonary failure (both unrelated to brexu-cel). At data cutoff, 44 of 78 patients had died with 20 patients (26%) alive and 14 patients (18%) who were lost to follow-up or withdrawn consent.

Overall, patients in ZUMA-3 experienced a survival benefit with a 40% 5-year OS rate. Patients benefitted from brexu-cel regardless of age, prior therapy, or subsequent alloSCT status, though small subgroups and unbalanced patient characteristics limited the interpretation of post hoc subgroup analyses.

Despite encouraging results, the researchers maintain: “New studies are needed to fully understand how prior therapies and subsequent alloSCT impact long-term outcomes in patients with R/R B-ALL treated with brexu-cel.”