Background: Brexu-cel is an established CD19-directed CAR-T cell therapy for relapsed or refractory mantle cell lymphoma, but clinical outcomes are heterogeneous, and germline determinants of response are poorly defined. Methods: We investigated the clinical impact of the CD19 single-nucleotide polymorphism rs2904880 on treatment outcome after brexu-cel CAR-T cell therapy by analyzing genotype-outcome associations in a retrospective single-center cohort of patients with relapsed or refractory mantle cell lymphoma treated with this CAR-T cell therapy. Results: Overall survival varied according to CD19 polymorphism, with improved survival of patients carrying the V174 homozygous genotype compared with L174V heterozygotes. Conclusions: The germline CD19 polymorphism may have implications for future risk stratification after brexu-cel CAR-T cell therapy in mantle cell lymphoma, but requires validation in larger, multicenter cohorts.