Orca-T administered prior to single-agent prophylaxis reduced rates of acute and chronic graft vs host disease (GVHD) while improving relapse and survival outcomes compared with historical controls, according to the results of pooled data from phase 1b and 2 studies presented at the 2023 Tandem Transplantation and Cellular Therapy Meetings of ASTCT and CIBMTR.

Orca-T is designed to control alloreactive immune responses. It is derived from allogeneic donors and consists of stem and immune cells. The aim of this study was to determine if Orca-T could improve rates of GVHD while maintaining graft responses against leukemic cells.

In this pooled analysis, 127 patients with acute leukemia or high-risk myelodysplastic syndrome were treated with Orca-T in a single-center phase 2 study or a multicenter phase 1b study. All patients received a myeloablative conditioning regimen that was busulfan- or TBI-based prior to the Orca-T infusion. Patients received GVHD prophylaxis with either tacrolimus or sirolimus.

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At baseline, the median age of the cohort was 48 and 57% of patients were male. In approximately half of cases, the donor was HLA-matched related, with the remaining unrelated.

Neutrophil and platelet engraftment occurred in a median of 13 and 16 days, respectively. There were 1.6% of patients who experienced graft failure. Grade 3 or higher acute GVHD developed among 5% of patients within the first year, and the rate of moderate to severe chronic GVHD was 6%. The non-relapse mortality rate was 5%.

In a historical control cohort from the CIBMTR, the rates of grade 3 or higher acute GVHD and moderate to severe chronic GVHD at 180 days were 16% and 38%, respectively. The non-relapse mortality rate was 10% at 1 year.

At 1 year and 18 months, the relapse-free survival was 81% with Orca-T. The 1-year and 18-month OS was 91% and 86%, respectively. In the historical control cohort, the 1-year RFS and OS were lower at 62% and 68%, respectively.

The authors concluded that “Orca-T demonstrate robust graph-versus-tumor and graft-versus-leukemia effects while markedly reducing GVHD and NRM despite myeloablative conditioning.” A phase 3 trial is currently enrolling.

Disclosures: This study was supported in part by Orca Biosystems, Inc. Please see the original reference for a full list of disclosures.


Oliai C, Hoeg RT, Pavlova A, et al. Precision-engineered cell therapy Orca-T demonstrates high relapse-free survival at 1 year while reducing graft-versus-host disease and toxicity. Presented at: 2023 Tandem Meetings Transplantation and Cellular Therapy Meetings of ASTCT and CIBMTR. February 15-19, 2023. Abstract 54.