# Clinical Impact of a LAG3 Single-Nucleotide Polymorphism in Relapsed, Refractory DLBCL Patients Treated with Glofitamab

## TL;DR

A genetic variant in the LAG3 gene is linked to better outcomes in lymphoma patients treated with glofitamab.

## Contribution

Identifies a LAG3 single-nucleotide polymorphism as a potential prognostic marker for glofitamab treatment in DLBCL.

## Key findings

- Homzygous LAG3 T455 carriers had extended progression-free and overall survival.
- Homozygous LAG3 I455 carriers showed shorter survival outcomes.
- CTLA4 genotype had no significant impact on treatment outcomes.

## Abstract

Glofitamab is a newly approved bispecific antibody for the treatment of relapsed, refractory diffuse large B-cell lymphoma. Treatment response may vary depending on the genetic background of the patient. Here, we evaluate clinical outcomes in patients with DLBCL treated with glofitamab according to LAG3 and CTLA4 genotypes. While there was no apparent clinical impact associated with the CTLA4 genotype, there was a significant association of the LAG3 genotype with clinical response. Future personalized therapeutic strategies may evolve in consideration of a specific LAG3 gene polymorphism.

Background: Glofitamab is a bispecific antibody engaging CD3 on T-cells and CD20 on B-cells. Glofitamab is approved for the treatment of relapsed, refractory diffuse large B-cell lymphoma (R/R DLBCL). Lymphocyte-activation gene 3 (LAG3) and T-lymphocyte-associated protein 4 (CTLA4) are immune checkpoint receptors with inhibitory effects on T-cell activity. There are several common germline variants of both receptor genes. Methods: Here, we evaluate clinical outcomes in R/R DLBCL patients treated with glofitamab according to the single-nucleotide polymorphisms LAG3 rs870849 and CTLA4 rs231775. Results: While there was no apparent association of CTLA4 genotype with glofitamab treatment outcomes, significant differences emerged in LAG3 rs870849 carriers with extended progression-free and overall survival in homozygous LAG3 T455, intermediate PFS and OS in heterozygous LAG3 I455T, and short PFS and OS in homozygous LAG3 I455 carriers. Conclusions: LAG3 rs870849 may be a prognostic response marker in R/R DLBCL treated with glofitamab.