FDA Approves Orca-T (Tregzi) for Matched Donor HSCT in Hematologic Malignancies

The FDA has approved allogeneic regulatory T cell–containing immunotherapy with hematopoietic stem and progenitor cell (HSPC) and T cells-vldq (Tregzi; Orca-T) for use in matched donor hematopoietic stem cell transplantation for adults with hematologic malignancies. The approval, granted June 30, 2026, was supported by data from the phase 3 Precision-T trial showing the cellular therapy reduced the risk of graft-versus-host disease across populations with acute myeloid leukemia, acute lymphoblastic leukemia, high-risk myelodysplastic syndrome, and mixed-phenotype acute leukemia.

According to Wendy Stock, MD, of the University of Chicago Medicine Comprehensive Cancer Center, the approval represents a "big advance" that needs to be studied further, including comparisons with post-transplant cyclophosphamide (PTCy). She said the decision may allow "higher-risk populations to move forward with the knowledge that it is possible to undergo transplant safely."

Orca-T is a cellular therapy product designed to modulate graft-versus-host disease by infusing regulatory T cells alongside stem cells, potentially enabling quicker immune reconstitution. This approach has never been used before in allogeneic transplant for the prevention of graft-versus-host disease. In the randomized, prospective Precision-T trial, results were "quite clear" in terms of benefit and primary end points of reducing graft-versus-host disease, with a suggestion of improved immune reconstitution and potentially better survival rates. The safety data were "very good," with no specific additional toxicity observed.

Stock noted that PTCy is "a totally different concept" and is not graft engineering per se, adding that whether Orca-T competes with PTCy must be answered prospectively. The Orca-T study enrolled a specific population: HLA-matched recipient and donor pairs in the myeloablative setting, without mismatched donors or reduced-intensity conditioning. It has been shown in a randomized trial to be more effective than not manipulating the graft, but it was not compared with PTCy.

Looking ahead, Stock emphasized referring patients early to transplantation and the importance of entering transplant with the lowest disease burden possible. She noted ongoing studies to improve preparative regimens and the potential for additional therapies after transplant to minimize relapse risk. The approval, she said, may inspire the field of transplant graft engineering to explore other options that could further improve transplantation outcomes.