Orca-T vs allogeneic hematopoietic stem cell transplantation (Precision-T): a multicenter, randomized phase 3 trial
Everett Meyer1, Amandeep Salhotra2, Arpita Gandhi3
1Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University School of Medicine, Stanford, CA.
Blood
|December 12, 2025
Summary
Orca-T immunotherapy significantly improved survival free from chronic graft-versus-host disease (GVHD) in patients undergoing allogeneic stem cell transplant. This novel approach demonstrated reduced toxicity and non-relapse mortality compared to conventional prophylaxis.
Area of Science:
- Hematology
- Immunology
- Oncology
Background:
- Conventional prophylaxis for graft-versus-host disease (GVHD) following myeloablative allogeneic hematopoietic stem cell transplantation (alloHSCT) involves calcineurin inhibitors plus methotrexate.
- Early studies indicated that Orca-T, an allogeneic T-cell immunotherapy utilizing donor regulatory T cells (Tregs), may prevent GVHD with reduced immunosuppression and improved outcomes.
Purpose of the Study:
- To compare the efficacy and safety of Orca-T immunotherapy versus conventional tacrolimus and methotrexate (Tac/MTX) prophylaxis for GVHD prevention in patients undergoing alloHSCT.
- To evaluate survival free from moderate-to-severe chronic GVHD (cGFS) as the primary endpoint.
Main Methods:
- A phase 3 randomized trial involving 187 adult patients with acute leukemias or myelodysplastic syndrome undergoing myeloablative conditioning.
- Patients received either Orca-T with tacrolimus or conventional Tac/MTX prophylaxis, utilizing G-CSF-mobilized peripheral blood from HLA-matched donors.
- Primary endpoint assessed using a stratified log-rank test for cGFS.
Main Results:
- Orca-T demonstrated significantly higher cGFS compared to Tac/MTX (78.0% vs 38.4% at one year; P<0.001).
- Cumulative incidence of moderate-to-severe chronic GVHD (cGVHD) was substantially lower with Orca-T (12.6% vs 44.0%; P<0.001).
- Orca-T showed improved GVHD and relapse-free survival (GRFS) (63.1% vs 30.9%; P<0.001) and reduced non-relapse mortality (NRM) (3.4% vs 13.2%; P=0.03).
Conclusions:
- Orca-T met its primary endpoint, establishing superior survival free from cGVHD compared to Tac/MTX prophylaxis.
- Orca-T represents a new therapeutic option for GVHD prophylaxis with significantly lower toxicity, including fewer serious infections and reduced NRM.
- The study supports Orca-T as a safe and effective alternative for GVHD prevention in alloHSCT.
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