A panelist discusses how advances in chronic graft-vs-host disease (cGVHD) prevention include posttransplant cyclophosphamide showing significant reduction in moderate to severe cGVHD and the promising Precision-T trial using split-dose infusions of regulatory T cells followed by conventional T cells, both demonstrating improved cGVHD-free survival compared with standard prophylaxis.
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Significant advances in chronic graft-vs-host disease (cGVHD) prophylaxis include 2 groundbreaking clinical trials. The BMT CTN 1703 study compared posttransplant cyclophosphamide (PTCy) with tacrolimus and mycophenolate mofetil vs standard tacrolimus/methotrexate in patients receiving reduced-intensity conditioning with peripheral blood stem cell grafts. The primary end point was 1-year graft-vs-host disease-free, relapse-free survival (GRFS). Results showed a significant reduction in moderate to severe cGVHD (approximately 20% in the PTCy arm), leading to improved GRFS of 53% at 1 year compared with 30% in the standard arm. These findings are driving practice changes, with many transplant centers now incorporating PTCy into their prophylaxis protocols for reduced-intensity transplants, including for mismatched unrelated donors, thereby expanding transplant access to minority populations.
The Precision-T trial, recently presented by Everett Meyer, MD, PhD, represents another major advancement in GVHD prevention. This randomized phase 3 study compared Orca-T (a precision-engineered graft) with standard unmanipulated grafts with tacrolimus/methotrexate prophylaxis in 160 patients receiving myeloablative conditioning. Orca-T’s innovative approach delivers CD34+ stem cells on day 0, followed by regulatory T cells and a lower dose of conventional T cells on day +2, with single-agent tacrolimus prophylaxis. The scientific rationale involves in vivo expansion of regulatory T cells that migrate to target organs, creating an immune barrier before conventional T cells arrive, thereby preventing GVHD development.
Results from the Precision-T trial were impressively positive, with 78% of patients receiving Orca-T remaining cGVHD-free at 1 year vs only 38% in the standard arm. GRFS at 1 year strongly favored Orca-T (68% vs 34%). The product is currently undergoing regulatory approval processes, with potential FDA approval anticipated in 2026 for patients with acute leukemia or hematologic malignancies undergoing myeloablative conditioning. These preventive strategies represent significant progress toward reducing the burden of cGVHD and improving long-term transplant outcomes for patients with hematologic malignancies requiring allogeneic transplantation.
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