A Retrospective Analysis Comparing Orca-T to Post-Transplant Cyclophosphamide Based Allogeneic Hematopoietic Cell Transplant in Patients with Matched Unrelated Donors Receiving Myeloablative Conditioning

Introduction Identifying an allogeneic hematopoietic cell transplantation (HCT) modality that can reduce graft versus host disease (GvHD), lower non-relapse mortality (NRM), and increase relapse free survival (RFS) is the key to improving outcomes for patients with hematologic malignancies.Recently, the utilization of post-transplant cyclophosphamide (PTCy) as a prophylaxis against GvHD has increased; however, PTCy-based HCTs after myeloablative conditioning are associated with higher toxicities requiring prolonged hospitalization, NRM and relapse at 1-year. Orca-T is a high-precision cell therapy biologic currently under investigation that includes stem and immune cells, derived from allogeneic donors, and leverages highly purified, polyclonal donor regulatory T cells to control alloreactive immune responses. Orca-T is administered with single agent tacrolimus as GvHD prophylaxis. To evaluate the relative efficacy of these treatment regimens, we compared them utilizing existing data from similar patient populations. Methods Publicly available data was obtained from CIBMTR (Gooptu et al, 2021) and included patients transplanted between 2011-2018 who met the following criteria: GvHD prophylaxis with PTCy and CNI/mycophenolate mofetil, ≥ 18, and AML or ALL in first or second CR, or MDS. Patients with matched unrelated donors (MUD) treated with myeloablative conditioning (MAC) and a GCSF-mobilized PBSC allograft between 2015 – 2018 were included. For comparison, patients ≥ 18 who received Orca-T between 2019-2022 as part of a multicenter Phase 1b single-arm trial (NCT04013685) were included if they had the following diagnosis: AML, ALL, or MPAL in CR/CRi or MDS; had an 8/8 MUD; and received MAC consistent with the Orca-T Phase 3 study (busulfan/fludarabine/thiotepa (BFT), total body irradiation (TBI)/Cy, or TBI/Etoposide). Results Baseline characteristics were similar across both groups for age, gender, and disease distribution (Table). The Orca-T group had a significantly higher DRI score.Orca-T demonstrated superior all grade chronic GvHD free survival compared to PTCy (73% vs 54%). 1-year NRM was lower with Orca-T vs PTCy (3% vs 16%). RFS (83% vs 62%) and overall survival (OS) (94% vs 77%) were higher at 1 year with Orca-T; notably, RFS and OS remained high at 2 years for patients treated with Orca-T. Conclusion Based on this retrospective analysis, Orca-T may improve post-HCT outcomes as compared to PTCy based MAC PBSC HCT in patients with acute leukemia and MDS. The positive impact on RFS, NRM and OS, in addition to reduced GvHD seen with Orca-T highlight the importance of identifying treatment approaches that may be beneficial across all key transplant outcomes. A randomized Phase 3 registrational trial evaluating Orca-T is currently ongoing (NCT05316701).