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Clinical Impact of a Germline CD19 Variant on Treatment Outcome After CAR-T Cell Therapy in Relapsed/Refractory Mantle Cell Lymphoma
by
, , and
Simona Andrea Ruckstuhl
1, 
Katja Seipel
1,2,*,
Inna Shaforostova
1,
Martina Bertschinger
1,
Ulrike Bacher
2,3
and
Thomas Pabst
1,*
1
Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland
2
Department for Biomedical Research (DBMR), University of Bern, 3008 Bern, Switzerland
3
Department of Hematology, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland
*
Authors to whom correspondence should be addressed.
Cancers 2026, 18(13), 2110; https://doi.org/10.3390/cancers18132110
Submission received: 3 June 2026
/
Revised: 25 June 2026
/
Accepted: 26 June 2026
/
Published: 29 June 2026
(This article belongs to the Special Issue Mantle Cell Lymphoma: Onwards and Upwards)
Simple Summary
Despite therapeutic advances, mantle cell lymphoma remains an incurable disease. CD19-directed CAR-T cell therapy can induce durable responses in patients with relapsed or refractory mantle cell lymphoma, but outcomes vary considerably. Germline variants of the CD19 gene may contribute to a heterogeneous response. In this study, we examined a common genetic variant in the CD19 gene in mantle cell lymphoma patients receiving brexu-cel, where the CD19 rs2904880 V174 homozygous genotype was associated with longer overall survival. This CD19 polymorphism may be relevant for future risk stratification in CD19-directed CAR-T cell therapy, but needs to be confirmed in larger, multicenter studies.
Abstract
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.
