ZUMA-3 trial: 5-year follow-up analysis of brexu-cel in adults with R/R B-ALL

Brexu-cel is an autologous anti-CD19 CAR T-cell therapy approved by the U.S. Food and Drug Administration and the European Union for the treatment of patients with R/R B-ALL aged ≥18 years and ≥26 years, respectively, based on results from the phase I/II ZUMA-3 trial (NCT02614066).¹ 

ZUMA-3 is a multicenter, single-arm trial assessing the efficacy and safety of brexu-cel in patients with R/R B-ALL. The ALL Hub previously reported the 3-year follow-up results from this trial. Five-year follow-up outcomes were presented by Oluwole at the 2025 EHA Annual Meeting (N = 78).¹ Outcomes included overall survival and safety in the overall population, as well as in subgroups defined by age, prior therapies, and subsequent allo-HSCT.¹

Key learnings 

In all patients, the 5-year OS rate was 40% with a median OS of 25.6 months, and a median OS of 53.5 months among responders (CR/CRi; n = 58). In patients aged ≥26 years (n = 63), the 5-year OS rate was 42%; among responders (CR/CRi), the median OS was 53.5 months.

Median and 5-year OS rates were lower in responders (n = 58) who subsequently proceeded to allo-HSCT (n = 14) vs those who did not proceed to allo-HSCT (n = 44); 50.2 months vs 60.4 months and 42% vs 52%, respectively.

The safety profile was consistent with previous reports; one new AE (cervical cancer) and death due to pulmonary failure (in the same patient) were reported since the 4-year analysis; both unrelated to brexu-cel. No secondary malignancies were reported.

The 5-year follow-up results demonstrate that brexu-cel continues to provide durable survival benefits for adult patients with R/R B-ALL, regardless of age, prior therapy, or subsequent allo-HSCT status.