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Donor Regulatory T-Cell Therapy to Prevent Graft-Versus-Host Disease.

Donor Regulatory T-Cell Therapy to Prevent Graft-Versus-Host Disease. Blood Meyer, E., Pavlova, A., Villar-Prados, A., Bader, C. S., Xie, B., Muffly, L., Kim, P., Sutherland, K. C., Bharadwaj, S., Dahiya, S., Frank, M. J., Arai, S., Johnston, L., Miklos, D. B., Rezvani, A. R., Shiraz, P., Sidana, S., Shizuru, J. A., Weng, W. K., Agrawal, V., Putnam, A., Fernhoff, N. B., Tamaresis, J., Lu, Y., Pawar, R. D., McClellan, J. S., Lowsky, R., Negrin, R. S. 2025

Abstract

Allogeneic hematopoietic cell transplantation (HCT) is a curative therapy limited by graft-versus-host disease (GVHD). In preclinical studies and early-phase clinical studies enrichment of donor regulatory T cells (Tregs) appears to prevent GVHD and promote healthy immunity.We enrolled 44 patients on an open-label, single-center, phase 2 efficacy study investigating if a precision selected and highly purified Treg cell therapy manufactured from donor mobilized peripheral blood improves one-year GVHD-free relapse free survival (GRFS) after myeloablative conditioning (trial NCT01660607). We compared this study arm to a concomitant standard of care (SOC) cohort. All donor Treg cell products were successfully manufactured and administered without cryopreservation within 72 hours. Participants had a one-year incidence of acute grade III-IV GVHD of 7%, moderate to severe chronic GVHD of 11% and non-relapse mortality rate of 4.5%. The primary endpoint of significantly improved one-year GRFS was achieved at 64% evaluated against a predicted incidence of 40% (p = 0.002) with a realized incidence of 36% in the SOC comparitor. For those trial patients whow developed grade II-IV acute GVHD, 91% responded to front-line steroid therapy wheras 50% responded in the SOC comparator group. Trial participants had a reduced incidence and burden of GVHD and improved GRFS, as compared to rates common to highly variable unmanipulated donor grafts and multi-agent immune suppression.

View details for DOI 10.1182/blood.2024026446

View details for PubMedID 39792934