Orca-T, an investigational allogeneic T-cell immunotherapy, led to better quality-of-life outcomes and lower healthcare resource use than standard treatment with conventional allograft with tacrolimus/methotrexate (Tac/MTX), according to the phase 3 Precision-T study of patients with blood cancers receiving myeloablative transplants from matched donors.
The results were published in Transplantation and Cellular Therapy.
Orca-T is an allogeneic stem cell and T-cell immunotherapy that leverages high-purity regulatory T cells to prevent graft-versus-host disease. It is individually manufactured for each transplant recipient, using cells collected from the mobilized peripheral blood of a single donor.
The phase 3 component of the Precision-T study is a randomized, open-label, multicenter study comparing outcomes between patients comparing Orca-T to a conventional allograft with Tac/MTX.
Previous results from the Precision-T study showed that Orca-T led to better patient outcomes by reducing chronic GVHD and improving survival compared to standard treatment. The new results compared health-related quality of life (HRQoL) and hospitalization patterns between arms.
HRQoL was measured using the FACT-BMT instrument (0–164 scale; higher scores indicate better HRQoL) at baseline and predefined intervals. A repeated measures model assessed change over time. Duration of initial hospitalization, rehospitalization rates, total hospitalized days, and rehospitalization-free survival were compared between arms.
In the study, eligible adults undergoing myeloablative allogeneic hematopoietic stem-cell transplantation (HSCT) for acute leukemia in complete remission, with intermediate- or high-disease risk index, or high-risk myelodysplastic syndrome (MDS) with ≤10% BM blasts, and human leukocyte antigens (HLA)-matched donors were randomized 1:1 to receive either Orca-T with single-agent tacrolimus or unmanipulated peripheral blood stem cells plus Tac/MTX.
The primary diseases included acute leukemia (53% myeloid, 30% lymphoblastic and 3% mixed phenotype) and high-risk MDS (14%).
Safety analyses included 88 Orca-T and 94 Tac/MTX patients, with grade 3–4 acute GVHD rates of 5.7% vs 9.6% and moderate–severe chronic GVHD of 12.5% vs 34.0%. Survey completion was >85% at baseline and approximately 66% at 1 year. FACT-BMT scores were consistently higher for Orca-T, with smaller declines at day 14 (−7.74 vs −13.69) and recovery above baseline by day 100 (1.34 vs −3.12), sustained through day 365.
Median hospitalization was 24.5 vs 24.0 days; rehospitalizations 27.3% vs 45.7%; total hospitalized days 30.6 vs 40.8; ICU admissions 1 vs 4. Rehospitalization-free survival at 18 months was 66.4% (95% CI 54.0–76.2) vs 33.8% (95% CI 18.5–49.9) (p = 0.0096; HR 0.53 [0.32–0.86]).
“Orca-T recipients experienced higher HRQoL, faster recovery, fewer ICU stays, lower rehospitalization rates, and improved rehospitalization-free survival compared to Tac/MTX, suggesting improved early post-transplant recovery and reduced GVHD symptom burden,” the authors wrote.
Funding was provided by Orca Bio.
Reference
Gandhi, A. et al. Orca-T Demonstrates Favorable Quality of Life and Healthcare Resource Use Compared to Standard Allohsct Plus Tac/MTX for GVHD Prevention in a Randomized phase 3 Clinical Trial (Precision-T). Transplantation and Cellular Therapy, Official Publication of the American Society for Transplantation and Cellular Therapy, Volume 32, Issue 2, S300
