Orca-T Improves Long-Term OS Survival vs Post-Transplant Cyclophosphamide in Hematologic Malignancies

Treatment with allogeneic regulatory T cell–based immunotherapy with hematopoietic stem and progenitor cell (HSPC) and T cells-vldq (Tregzi; Orca-T) was associated with improved long-term overall survival (OS) compared with registry-based post-transplant cyclophosphamide (PTCy)–based graft-vs-host disease (GVHD) prophylaxis in adult patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematologic malignancies, according to an observational analysis published in Transplantation and Cellular Therapy.¹

The comparison drew on patients treated in the phase 1b Orca-T trial (NCT04013685) and a contemporaneous cohort from the Center for International Blood and Marrow Transplant Research (CIBMTR)/National Marrow Donor Program (NMDP) registry.

Findings showed that among patients who received Orca-T (n = 76), the 3-year OS rate was 83% (95% CI, 73%-90%) compared with 66% (95% CI, 60%-71%) for patients in the PTCy cohort (n = 360; HR, 0.41; log-rank P = .003). The 2-year OS rates were 86% (95% CI, 76%-92%) vs 72% (95% CI, 67%-77%), respectively, and the 1-year OS rates were 96% (95% CI, 88%-99%) vs 81% (95% CI, 77%-85%).

In a propensity score–matched analysis (n = 76 per group), the OS benefit was maintained (HR, 0.40; log-rank P = .010), with 3-year OS rates of 83.4% vs 67.4%. A multivariable Cox model adjusting for baseline characteristics yielded an HR of 0.38 (95% CI, 0.21-0.71; P = .002).

“While there are treatment options available to help prevent GVHD, data on the impact of them on overall survival have been limited. The findings from this retrospective analysis on the recently approved therapy, [Orca-T], point to the value of cell therapy in potentially improving transplant outcomes for patients without sacrificing long-term survival,” Caspian H. Oliai, MD, medical director of the UCLA Bone Marrow Transplantation Stem Cell Processing Center, stated in a news release.²

How was the analysis conducted?

The analysis compared patients treated with Orca-T in the multicenter phase 1b trial with a registry-based cohort of patients who received conventional allo-HSCT with PTCy-based GVHD prophylaxis. Eligible patients were adults 65 years of age or younger with intermediate- or high-risk acute myeloid leukemia, acute lymphoblastic leukemia in complete remission, or myelodysplastic syndromes who underwent myeloablative conditioning and received a graft from an 8/8 HLA-matched donor.

The median age was 48 years in the Orca-T group and 49 years in the PTCy cohort, and a Hematopoietic Cell Transplantation–specific Comorbidity Index score of 2 or lower was reported in 68% and 64% of patients, respectively.

The median follow-up was 42 months (interquartile range [IQR], 36-47) for Orca-T and 33 months (IQR, 24-37) for the PTCy cohort. Orca-T is a personalized cell therapy comprising highly purified regulatory T cells to suppress GVHD, HSPCs to reconstitute the immune system, and conventional T cells to accelerate immune recovery.

What did data for secondary end points show?

The 3-year nonrelapse mortality (NRM) rate was 3.1% with Orca-T vs 10% with PTCy (Gray’s P = .0497; HR, 0.27); in the propensity score–matched comparison, the 3-year NRM rates were 3.1% vs 16%. The 3-year relapse rate was 26% (95% CI, 16%-37%) with Orca-T vs 32% (95% CI, 27%-38%) with PTCy (HR, 0.72; P = .324), and the median time to relapse was 9.9 months vs 6.2 months, respectively. Relapse-free survival at 3 years was 71% (95% CI, 58%-80%) with Orca-T vs 57% (95% CI, 51%-63%) with PTCy (HR, 0.60; P = .034).

All patients who received Orca-T achieved neutrophil engraftment, at a median of 12 days (range, 10-24), with no cases of primary graft failure. Among the 13 deaths in the Orca-T group, 12 (92%) were attributed to relapse or disease progression and 1 (8%) to GVHD, with no deaths attributed to infection or organ failure and toxicity.

What is the context for these data?

Orca-T received FDA approval in June 2026 for use in matched donor HSCT with a myeloablative preparative regimen in adults with hematologic malignancies, a decision supported by the phase 3 Precision-T trial (NCT05316701).³ The present observational analysis adds long-term survival data drawn from the earlier phase 1b experience, benchmarked against registry outcomes with contemporary PTCy-based prophylaxis.¹

References

1. Oliai CH, Gandhi A, Hoeg RT, et al. Observational comparison of overall survival between phase 1b Orca-T and registry-based post-transplant cyclophosphamide patients. Transplant Cell Ther. Published online August 21, 2026. doi:10.1016/j.jtct.2026.08.037
2. Orca Bio announces the publication of TREGZI long-term overall survival data in Transplantation and Cellular Therapy. News release. Orca Bio. September 17, 2026. Accessed September 17, 2026. https://www.businesswire.com/news/home/20260917410797/en/Orca-Bio-Announces-the-Publication-of-TREGZI-Long-Term-Overall-Survival-Data-in-Transplantation-and-Cellular-Therapy
3. FDA approves Orca-T for matched donor HSCT in hematologic malignancies. OncLive. Published June 30, 2026. Accessed September 17, 2026. https://www.onclive.com/view/fda-approves-orca-t-for-matched-donor-hsct-in-hematologic-malignancies