FDA Approves Orca-T After Phase 3 Trial Improves Chronic GVHD-Free Survival

On June 30, 2026, the US Food and Drug Administration (FDA) approved precision-engineered allogeneic regulatory T-cell therapy, Orca-T®, (Tregzi) for adults with hematological malignancies undergoing matched-donor allogeneic hematopoietic stem cell transplantation (alloHSCT), following results from the randomized phase 3 Precision-T trial.

Phase 3 Precision-T Trial

The study enrolled 187 patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), high-risk myelodysplastic syndrome (MDS), and mixed-phenotype acute leukemia (MPAL) and evaluated the therapy plus tacrolimus compared with conventional alloHSCT plus tacrolimus and methotrexate.

At 12 months, the therapy demonstrated a significant improvement in chronic graft-versus-host disease (GVHD)-free survival, the study’s primary endpoint, with rates of 78% compared with 38.4% for conventional alloHSCT (hazard ratio [HR], 0.26; 95% Confidence Interval [CI], 0.14-0.47; P <.001).

The benefit was driven by reduced rates of moderate-to-severe chronic GVHD and fewer deaths, with additional improvements observed in GVHD-free relapse-free survival and nonrelapse mortality. Overall survival was 93.9% with the precision-engineered therapy compared with 83.1% with conventional alloHSCT, although the difference was not statistically significant.

Orca-T uses matched donor-derived hematopoietic stem and progenitor cells, highly purified regulatory T cells, and conventional T cells designed to support immune reconstitution, reduce GVHD, and preserve graft-versus-leukemia activity.

Q&A: HCPLive talks to Wendy Stock, MD, the Anjuli Seth Nayak Professor of Leukemia Research, hematology/oncology, and director of the Leukemia Program at the University of Chicago.

HCPLive: How clinically meaningful are the improvements in overall survival and relapse-free survival observed with Orca-T compared with post-transplant cyclophosphamide in the phase 3 Precision-T study?

I think it looks very promising, but we do not know that for sure yet because a direct comparison needs to be done prospectively. If the survival data from the Orca-T study hold up with longer follow-up, that will be very encouraging because overall survival will be an important measure of success in addition to chronic graft-versus-host disease-free survival.

Ultimately, we need prospective studies comparing patients treated with these different strategies to better understand how they compare.

HCPLive: The Precision-T study reported 0% nonrelapse mortality at 1 year among patients treated with Orca-T. How should clinicians interpret this finding when considering the role of this therapy in transplant practice?

Orca-T has now been approved, and I think it is very encouraging to see the very low rates of graft-versus-host disease observed with this product. It represents a significant advance.

That said, it is not an inexpensive advance, and it requires an additional technical approach. However, we know that allogeneic transplantation can improve outcomes for patients, and if we can make the process safer and more applicable to more patients, that is an important goal. We want to improve survival without causing a significant amount of toxicity.

HCPLive: Now that Orca-T is approved, where do you see it fitting into current transplant pathways alongside established approaches such as post-transplant cyclophosphamide?

That is an important question, and we do not know the full answer yet. The available evidence comes from the population studied in the trial: patients receiving HLA-matched related or unrelated donor transplants.

This represents an important group of patients because we still see a significant burden of graft-versus-host disease in this setting. Post-transplant cyclophosphamide is certainly a less expensive approach, and we do not yet know whether Orca-T provides equivalent or superior outcomes in terms of relapse-free survival or other important endpoints.

For patients who meet the criteria studied in the trial, Orca-T represents an intriguing option if transplant centers are able to meet the requirements needed to use the product.

HCPLive: Based on the available data, which patients may be the best candidates for Orca-T in routine clinical practice?

Right now, the best candidates are the patients who were studied in the clinical trial: those undergoing HLA-matched related or unrelated donor transplantation.

We do not yet have evidence for other populations, including patients with greater HLA mismatches. The data we have currently support use in the population that was evaluated.

How does Orca-T influence the balance between reducing graft-versus-host disease while maintaining graft-versus-leukemia activity?

That is the promise of this product. We have seen reductions in graft-versus-host disease, and the next step is ensuring that the graft-versus-leukemia effect remains durable with longer follow-up and additional prospective studies.

The ability to reduce transplant-related toxicity while maintaining anti-leukemia activity would be a very exciting advancement.

HCPLive: What unanswered questions remain following FDA approval of Orca-T?

There are several important questions. We do not yet know whether this approach will be applicable to patients with greater HLA mismatches, and we do not yet know whether it is better or equivalent to post-transplant cyclophosphamide in the populations that have been studied.

Longer follow-up will be important to confirm that the graft-versus-leukemia effect remains as promising as it appears in early data. Reducing graft-versus-host disease is incredibly important because long-term survival is not possible if patients die from transplant complications, including infectious complications.

Ultimately, we need to confirm that Orca-T can provide both reduced toxicity and a strong anti-disease effect.

What additional considerations should clinicians keep in mind as Orca-T enters clinical practice?

I think this is a major advance, but it is also an expensive advance. We will have to see whether insurers are willing to cover it. The cost will add substantially to transplantation, and that will be an important consideration.

Clinicians and insurers will likely want to see longer-term data, but this represents an exciting opportunity to manipulate the graft in a way that may reduce toxicity while maintaining or improving anti-leukemia effects.

References:

1. Meyer EH, Salhotra A, Gandhi AP, et al. Orca-T vs allogeneic hematopoietic stem cell transplantation (Precision-T): a multicenter, randomized phase 3 trial. Blood. 2026;147(11):1168-1177. doi:10.1182/blood.2025031313.

2. US Food and Drug Administration. FDA approves new treatment that uses donor immune cells to prevent serious complications in blood cancer patients. Published June 30, 2026. Accessed July 14, 2026.

3. US Food and Drug Administration. TREGZI (allogeneic regulatory T cell immunotherapy with HSPC and T cells-vldq): prescribing information. Published July 2026. Accessed July 14, 2026