In the editorial titled “Naïve T-Cell Depletion to Prevent GVHD: Searching for a Better Mousetrap,” published in the Journal of Clinical Oncology, Dr. Robert Soiffer discusses targeted T cell depletion (TCD) strategies to prevent chronic graft-versus-host disease (cGVHD). Citing a recently published article which looked at three separate trials (Bleakley et al, 2022), depletion of naïve CD45RA+ T cells was associated with low rates of GVHD and nonrelapse mortality (NRM). Therefore, Dr. Soiffer suggests that, although a randomized trial is required, TCD holds promise for lowering GVHD and NRM.

To prevent GVHD, graft engineering has been explored but not yielded improved survival outcomes in four decades. Throughout the years, several studies exploring TCD found some improvements for GVHD, but no increases in NRM or overall survival (OS). While these studies performed pan TCD with broad monoclonal antibodies, elutriation, or CD34-positive selection, Bleakley et al used a novel naïve CD45RA depletion strategy.

Comparing CD34 selection alone to CD34-selected graft plus addback of the CD45RA T cell–depleted CD34-negative product, there appears to be lower NRM, GVHD, and better disease-free survival (DFS) with the latter. Thus, Dr. Soiffer speculates that improved TCD strategies will ultimately yield results superior to conventional approaches in use today to prevent GVHD.

References

Bleakley M, Sehgal A, Seropian S, et al. Naive T-Cell Depletion to Prevent Chronic Graft-Versus-Host Disease [published online ahead of print, 2022 Jan 10]. J Clin Oncol. 2022;JCO2101755.

https://doi.org/10.1200/JCO.21.01755

Soiffer RJ. Naïve T-Cell Depletion to Prevent GVHD: Searching for a Better Mousetrap [published online ahead of print, 2022 Feb 25]. J Clin Oncol. 2022;JCO2200105. https://doi.org/10.1200/JCO.22.00105

Tags: GVHD, transplantation, Prevention, cell therapy, T-Cell, graft-versus-host disease, clinical oncology, t-cell depletion, naive t-cell