Donor regulatory T-cell therapy to prevent graft-versus-host disease

Allogeneic hematopoietic cell transplantation 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 in an open-label, single-center, phase 2 efficacy study investigating if a precision selected and highly purified Treg therapy manufactured from donor-mobilized peripheral blood improves 1-year GVHD-free relapse-free survival (GRFS) after myeloablative conditioning. We compared this study arm with a concomitant standard-of-care (SOC) cohort. All donor Treg products were successfully manufactured and administered without cryopreservation within 72 hours. Participants had a 1-year incidence of acute grade 3 to 4 GVHD of 7%, moderate to severe chronic GVHD of 11%, and nonrelapse mortality rate of 4.5%. The primary end point of significantly improved 1-year GRFS was achieved at 64% evaluated against a predicted incidence of 40% (P = .002) with a realized incidence of 36% in the SOC comparator. For those trial patients who developed grade 2 to 4 acute GVHD, 91% responded to front-line corticosteroid therapy, whereas 50% responded in the SOC comparator group. Trial participants had a reduced incidence and burden of GVHD and improved GRFS, compared with rates common to highly variable unmanipulated donor grafts and multiagent immune suppression. This trial was registered at www.clinicaltrials.gov as #NCT01660607.

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Publication Details

Journal
Blood
Published
2025-01-10
DOI
https://doi.org/10.1182/blood.2024026446
Citations
31
Primary Topic
Hematopoietic Stem Cell Transplantation
Type
article
Field-Weighted Citation Impact
54.87

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Donor regulatory T-cell therapy to prevent graft-versus-host disease

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Blood
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Donor regulatory T-cell therapy to prevent graft-versus-host disease

Parveen Shiraz, Lori S. Muffly, Robert S. Negrin, Alejandro Villar‐Prados, James Scott McClellan, Judith A. Shizuru, Sushma Bharadwaj, Vaibhav Agrawal, Surbhi Sidana, Saurabh Dahiya, Cameron S. Bader, Matthew J. Frank, Robert Lowsky, Sally Arai, Nathaniel B. Fernhoff, Laura Johnston, John Tamaresis, Ying Lü, Anna Pavlova, Andrew R. Rezvani, Amy Putnam, David B. Miklos, Everett Meyer, Bryan J. Xie, Paul Kim, Rahul Pawar, Katherine C. Sutherland, Wen-Kai Weng
article en
31 citations

Abstract

Allogeneic hematopoietic cell transplantation 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 in an open-label, single-center, phase 2 efficacy study investigating if a precision selected and highly purified Treg therapy manufactured from donor-mobilized peripheral blood improves 1-year GVHD-free relapse-free survival (GRFS) after myeloablative conditioning. We compared this study arm with a concomitant standard-of-care (SOC) cohort. All donor Treg products were successfully manufactured and administered without cryopreservation within 72 hours. Participants had a 1-year incidence of acute grade 3 to 4 GVHD of 7%, moderate to severe chronic GVHD of 11%, and nonrelapse mortality rate of 4.5%. The primary end point of significantly improved 1-year GRFS was achieved at 64% evaluated against a predicted incidence of 40% (P = .002) with a realized incidence of 36% in the SOC comparator. For those trial patients who developed grade 2 to 4 acute GVHD, 91% responded to front-line corticosteroid therapy, whereas 50% responded in the SOC comparator group. Trial participants had a reduced incidence and burden of GVHD and improved GRFS, compared with rates common to highly variable unmanipulated donor grafts and multiagent immune suppression. This trial was registered at www.clinicaltrials.gov as #NCT01660607.

BloodVol. 145(18)
City Of Hope National Medical Center (US), Palo Alto University (US), Menlo School (US), City of Hope (US), Meta (United States) (US), Stanford Blood Center (US), Stanford Medicine (US), Stanford University (US)
National Institutes of Health
Good health and well-being
Openalex Percentile: Top 0%
Hematopoietic Stem Cell Transplantation
54.87
DOIOpen Access PDFOpenAlex
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