# Disease Stage-Dependent Clinical Impact of CTLA4 Polymorphism in Multiple Myeloma Treated with Autologous Stem Cell Transplantation

## TL;DR

A genetic variant in the CTLA4 gene affects treatment outcomes in multiple myeloma patients depending on disease stage.

## Contribution

The study reveals that the CTLA4 rs231775 AA genotype has stage-dependent clinical effects in multiple myeloma after stem cell transplantation.

## Key findings

- The CTLA4 rs231775 AA genotype is linked to worse outcomes in early- and intermediate-stage multiple myeloma.
- The same genotype is associated with better outcomes in late-stage multiple myeloma.
- The polymorphism may help refine risk stratification and personalize treatment after stem cell transplantation.

## Abstract

Despite therapeutic advances, multiple myeloma is incurable, with highly variable clinical outcomes. Inherited variants of immune regulatory genes can modulate disease susceptibility and clinical outcomes. In this study, we investigated a specific polymorphism of the immune checkpoint gene, CTLA4, in myeloma patients undergoing autologous stem cell transplantation. The CTLA4 rs231775 AA genotype was associated with inferior outcomes in early- and intermediate-stage disease and superior outcomes in late-stage disease. The CTLA4 rs231775 polymorphism may contribute to post-transplant immune regulation, risk stratification, and personalized medicine approaches.

Background: Clinical outcomes for multiple myeloma are highly variable. Inherited genetic variants of immune regulatory genes can modulate disease susceptibility and clinical outcomes. The germline variant CTLA4 rs231775 polymorphism may alter T-cell function and affect clinical outcomes. Methods: We conducted a retrospective single-center study including 156 consecutive myeloma patients who underwent first-line ASCT. The patients were stratified according to the CTLA4 rs231775 genotype and disease stage (ISS I–III). Results: The CTLA4 rs231775 AA genotype was associated with inferior PFS in ISS I–II and superior PFS in ISS III. In the multivariate analysis, the CTLA4 rs231775 AA genotype emerged as a potential risk factor in ISS I-II and a potential protective factor in ISS III. Conclusions: This germline CTLA4 polymorphism may serve as biomarker to refine post-transplant risk stratification and enable personalized treatment management.