Orca-T With Myeloablative Conditioning Yields Increased Survival, Lowered NRM in Hematologic Malignancies

Treatment with Orca-T was associated with improvements in relapse-free survival (RFS) and overall survival (OS), as well as lower rates of non-relapse mortality (NRM), compared with post-transplant cyclophosphamide (PTCy) in patients with hematologic malignancies who also received myeloablative conditioning, according to data from an observational comparison presented at the 2026 Transplantation & Cellular Therapy Meetings.¹

The observational study included patients (n = 164) treated in the Orca-T arm of the phase 3 Precision-T trial (NCT05316701); patients (n = 76) who received Orca-T in a phase 1b trial (NCT04013685) and met eligibility criteria for the phase 3 study; and patients (n = 380) from the CIBMTR registry who received PTCy plus tacrolimus with or without mycophenolate mofetil and had similar clinical profiles compared with patients treated with Orca-T.

Findings showed that patients treated with Orca-T (n = 164) experienced improvements in OS (P < .001) and RFS (P = .045), as well as decreased rates of NRM (P = .033) vs those given PTCy. Within the Orca-T cohort, the 1-, 2-, and 3-year OS rates were 94% (95% CI, 89%-97%), 85% (95% CI, 76%-90%), and 82% (95% CI, 72%-88%), respectively. These respective rates in the PTCy cohort were 82% (95% CI, 78%-86%), 73% (95% CI, 68%-77%), and 65% (95% CI, 60%-70%).

The 1-year RFS rate was 78% (95% CI, 70%-84%) in the Orca-T cohort vs 70% (95% CI, 65%-74%) in the PTCy cohort. The respective 1-year NRM rates were 2.7% (95% CI, 0.87%-6.4%) vs 7.7% (95% CI, 5.3%-11%).

“In the context of myeloablative conditioning, [patients treated with] Orca-T, in comparison [with patients treated with PTCy from] the CIBMTR registry, exhibited increased OS, increased RFS, and decreased NRM,” lead study author Amandeep Salhotra, MD, and colleagues wrote in a poster presentation of the data. “[These data suggest that] Orca-T may improve hematopoietic stem cell transplant [HCT] survival in the myeloablative conditioning setting.”

Salhotra is an associate professor in the Division of Leukemia of the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope in Duarte, California.

How was this observational comparison of Orca-T conducted?

For the Orca-T cohort, investigators pooled data from the phase 1b trial and the phase 3 Precision-T trial, which both investigated the novel allogeneic immunotherapy in patients with hematologic malignancies. Notably, the FDA granted priority review to a biologics license application seeking the approval of Orca-T for the treatment of select patients with hematologic malignancies, including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplastic syndromes (MDS), in October 2025 based on prior data from Precision-T.²

Patient data from the control arm of the observational study were pulled from the CIBMTR registry.¹ Patients in both cohorts needed to be 18 to 65 years of age with intermediate- to high-risk AML or ALL in complete remission, or MDS. Myeloablative conditioning was required, and patients needed to have 8/8 HLA-matched donors.

Investigators used the data to access OS, RFS, and NRM outcomes between the 2 groups.

Patients in the Orca-T group had a median age of 47 years (range, 35-56) compared with 49 years (range, 38-58) in the PTCy group. The majority of patients were male (Orca-T, 57%; PTCy, 58%), were White (75%; 84%), were non-Hispanic (75%; 82%), had a Karnofsky performance status of at least 90 (76%; 65%), had an intermediate disease-risk index (81%; 87%), had AML (55%; 50%), had matched, unrelated donors (50%; 82%), had an HCT comorbidity index score of 2 or less (74%; 64%), and had peripheral blood as a graft source (100%; 90%). All patients in the PTCy group received HCT between 2019 and 2021; 34% of patients in the Orca-T arm were treated from 2019 to 2021, and the remaining 66% were treated between 2002 and 2024.

What outcomes were reported for patients older than 50 years of age?

Investigators also assessed OS outcomes across a variety of subgroups, and findings were consistent for Orca-T vs post-transplant cyclophosphamide.

Specifically for patients over 50 years of age, improvements were observed with Orca-T (n = 67) vs PTCy (n = 177) in regard to OS (P = .034), RFS (P = .2), and NRM (P = .048). The 1-, 2-, and 3-year OS rates in patients over 50 years of age treated with Orca-T were 95% (95% CI, 86%-98%), 82% (95% CI, 67%-90%), and 79% (95% CI, 63%-88%), respectively. These respective rates in the PTCy cohort were 77% (95% CI, 71%-83%), 70% (95% CI, 62%-76%), and 65% (95% CI, 57%-72%).

The 1-year RFS rate was 76% (95% CI, 63%-85%) in patients over 50 years of age treated with Orca-T vs 68% (95% CI, 60%-74%) for those given post-transplant cyclophosphamide. The 1-year NRM rates were 3.0% (95% CI, 0.56%-9.4%) and 12% (95% CI, 7.7%-17%), respectively.

References

1. Salhotra A, Tamari R, Oliai C, et al. Clinical outcomes in Orca-T and registry-based post-transplant cyclophosphamide patients: an observational comparison. Presented at: 2026 Transplantation & Cellular Therapy Meetings; February 4-7, 2026; Salt Lake City, UT. Abstract 366.
2. Orca Bio announces FDA acceptance and priority review of the biologics license application (BLA) for Orca-T to treat hematological malignancies. News release. Orca Bio. October 6, 2025. Accessed February 9, 2026. https://orcabio.com/orca-bio-announces-fda-acceptance-and-priority-review-of-the-biologics-license-application-bla-for-orca-t-to-treat-hematological-malignancies/