Dr Gomez Arteaga on an Investigation of Orca-T Vs PTCy-Based HCT in Acute Leukemia and MDS

Alexandra Gomez Arteaga, MD, assistant professor of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine/New York-Presbyterian Hospital, discusses the relative efficacy of the high-precision cell therapy Orca-T vs standard post-transplant cyclophosphamide (PTCy)–based therapy when administered after myeloablative conditioning, according to findings from a retrospective analysis presented during the 2024 Transplantation & Cellular Therapy Meetings.

Published data on PTCy is currently heterogeneous, with varying methodologies across studies, including the use of bone marrow grafts and different immunosuppression regimens, Gomez Arteaga begins. To address this heterogeneity, a retrospective cohort analysis was conducted to compare outcomes with Orca-T vs standard PTCy in patients with acute leukemia and myelodysplastic syndromes (MDS), Gomez Arteaga details. One cohort of the study comprised adults who had received Orca-T between 2019 and 2022 as part of a multicenter phase 1b single-arm trial (NCT04013685) and had acute myeloid leukemia, acute lymphocytic leukemia, mixed phenotype acute leukemia in complete remission, or MDS. Patients with matched unrelated donors treated with myeloablative conditioning and a granulocyte colony-stimulating factor mobilized peripheral blood progenitor cell allograft between 2015 and 2018 were included in acomparator cohort.

Findings presented at the 2024 Transplantation & Cellular Therapy Meetings showed that Orca-T improved relapse-free survival (RFS), non-relapse mortality (NRM), and overall survival (OS) and reduced chronic GVHD (cGVHD) rates compared with PTCy myeloablative conditioning, Gomez Arteaga reports. Patients who received Orca-T achieved an RFS rate of 77%, an NRM rate of 3%, and an OS rate of 94%. Corresponding rates in the patients who received PTCy were 62% (HR, 0.5; 95% CI, 0.3-0.9), 16% (HR, 0.2; 95% CI, 0.0-0.5), and 77% (HR, 0.2; 95% CI, 0.1-0.6).

These findings indicate that Orca-T may offer advantages over PTCy, particularly in reducing the incidence of cGVHD, Gomez Arteaga states. Beyond its potential impact on cGVHD, Orca-T appears to improve other key survival outcomes, underscoring the importance of refining GVHD prophylaxis strategies to minimize associated toxicities, she emphasizes. Overall, the results of this retrospective analysis highlight the need for continued improvement in GVHD prophylaxis methods through further clinical study, Gomez Arteaga concludes.