Safety and efficacy of brexu-cel in R/R CNS B-cell ALL: A real-world study

Brexu-cel, a CD19 CAR T-cell therapy, is approved for the treatment of adults with R/R B-cell ALL, based on results of the phase I/II ZUMA-3 trial (NCT02614066). The ZUMA-3 trial excluded patients with symptomatic CNS-2 and CNS-3 disease, highlighting a need for evaluation of brexu-cel in this population. Muhsen et al. published the results of a real-world study evaluating the safety and efficacy of brexu-cel in patients with R/R CNS B-cell ALL in Blood Advances.¹  The trial excluded patients with symptomatic CNS-2 and CNS-3 disease, highlighting a need for evaluation of brexu-cel in this population. Muhsen et al. published results of a real-world study evaluating the safety and efficacy of brexu-cel in patients with R/R CNS B-cell ALL in Blood Advances.¹   

The study comprised data from the ROCCA database of adult patients with R/R B-cell ALL (N = 189) who received brexu-cel between October 2021 and August 2023. The CNS group (n = 31) was defined as patients with/without medullary disease at the time of pre-apheresis disease assessment (non-CNS group, n = 158). Key safety outcomes included CRS and ICANS, and efficacy outcomes included CNS response rates, PFS, and OS.  

Key learnings 

In the CNS group, 3.2% and 35.5% of patients developed Grade 3–4 CRS and ICANS vs 12.0% and 30%, respectively, in the non-CNS group.

CR rates (93.3% vs 89.1%) and MRD-negative remission rates (83.3% vs 68.1%) were similar in the CNS and non-CNS groups, respectively.

In the CNS group, 87.5% of patients achieved CNS-1 with brexu-cel vs 75.0% in patients with CNS-3.

There were no differences in PFS (p = 0.83) and OS (p = 0.14) between the CNS and the non-CNS groups. 

The findings demonstrate that brexu-cel is a feasible treatment option for patients with R/R CNS B-cell ALL, and underscore the need to optimize CAR T-cell treatments in this population.