# T cell phenotype and clonality changes in myeloma patients with short overall survival

## TL;DR

Myeloma patients with shorter survival show changes in T cells, including fewer T cells and more exhausted clones, compared to those with longer survival.

## Contribution

Identifies T cell and clonality changes associated with short overall survival in myeloma patients.

## Key findings

- Short-OS patients had fewer T cells and more Tregs and exhausted CD8+ T cells at relapse.
- Higher PD-1 expression in CD8+ T cells at diagnosis correlated with shorter survival.
- Short-OS patients showed a more monoclonal T cell environment with hyperexpanded clones at relapse.

## Abstract

Overall survival (OS) in multiple myeloma (MM) varies between a couple of months to more than 20 years, influenced by tumor characteristics, the tumor microenvironment (TME), and patient factors such as age and frailty. We analyzed sequential BM samples from 45 MM patients with OS less than 3 years versus more than 8 years using mass cytometry and bulk TCRβ sequencing. Patients with long OS demonstrated stability in the TME and T cell environments, while those with short OS had significant changes at relapse, including fewer T cells, increased Tregs, and more activated and exhausted CD8+ T cells. Notably, higher programmed cell death 1 expression in CD8+ T cells at diagnosis correlated with short OS. Additionally, short-OS patients exhibited a more monoclonal T cell environment at relapse, with abundance of hyperexpanded clones. These findings reveal distinct immune cell differences between patients with short and long OS.

Shorter survival in myeloma patients linked to T-cell changes, including fewer T cells and hyperexpanded T cell clones.