Orca-T vs allogeneic hematopoietic stem cell transplantation (Precision-T): a multicenter, randomized phase 3 trial

To prevent graft-versus-host disease (GVHD) in patients undergoing myeloablative allogeneic hematopoietic stem cell transplantation (alloHSCT), a calcineurin inhibitor plus methotrexate is routinely used. Early phase studies suggested improved outcomes with Orca-T, an allogeneic T-cell immunotherapy that uses purified donor regulatory T cells to prevent GVHD with significantly less immunosuppression. This phase 3 trial randomized adult patients (N = 187) with acute leukemias or myelodysplastic syndrome undergoing myeloablative conditioning to receive either Orca-T with tacrolimus or a conventional allograft with tacrolimus and methotrexate (Tac/MTX), using granulocyte colony-stimulating factor-mobilized peripheral blood from HLA-matched donors. The primary end point was survival free from moderate-to-severe chronic GVHD (cGVHD; cGFS). Using a stratified log-rank test, cGFS was significantly higher in the Orca-T arm than in Tac/MTX (hazard ratio, 0.26; 95% confidence interval, 0.14-0.47; P< .001). One-year estimates were as follows: cGFS was 78.0% with Orca-T vs 38.4% with Tac/MTX; cumulative incidence of moderate-to-severe cGVHD was 12.6% with Orca-T and 44.0% with Tac/MTX (Gray test P< .001); overall survival was 93.9% with Orca-T vs 83.1% with Tac/MTX (P = .12); GVHD-free and relapse-free survival was 63.1% and 30.9% in the Orca-T and Tac/MTX arms (P< .001), respectively; nonrelapse mortality (NRM) was 3.4% with Orca-T vs 13.2% with Tac/MTX (P = .03). Orca-T met the primary end point of improved survival free from cGVHD compared with Tac/MTX prophylaxis and should be considered a new therapeutic option with low toxicity for GVHD prophylaxis. Moreover, significantly less toxicity was observed with Orca-T patients, including fewer serious infectious complications and less NRM. This trial was registered at www.clinicaltrials.gov as NCT05316701.

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Publication Details

Journal
Blood
Published
2025-12-12
DOI
https://doi.org/10.1182/blood.2025031313
Citations
5
Primary Topic
Hematopoietic Stem Cell Transplantation
Type
article
Field-Weighted Citation Impact
8.85

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article

Orca-T vs allogeneic hematopoietic stem cell transplantation (Precision-T): a multicenter, randomized phase 3 trial

Rawan Faramand, Robert S. Negrin, John M. Murray, John Magenau et al.
5 citations
Blood
Hematopoietic Stem Cell Transplantation
8.85
article

Orca-T vs allogeneic hematopoietic stem cell transplantation (Precision-T): a multicenter, randomized phase 3 trial

Rawan Faramand, Robert S. Negrin, John M. Murray, John Magenau, Antonio Jiménez, Edmund K. Waller, James Scott McClellan, Yi‐Bin Chen, Caspian Oliai, Alireza Eghtedar, Arpita P. Gandhi, Sagar S. Patel, Jennifer Holter‐Chakrabarty, Betty K. Hamilton, Nathaniel B. Fernhoff, Rasmus T. Hoeg, M. Scott Killian, Bhagirathbhai Dholaria, Alexandra Gomez-Arteaga, Amandeep Salhotra, Anna Pavlova, Jeremy Pantin, Everett Meyer, Roni Tamari, Li Ai, Satyajit Kosuri
article en
5 citations

Abstract

To prevent graft-versus-host disease (GVHD) in patients undergoing myeloablative allogeneic hematopoietic stem cell transplantation (alloHSCT), a calcineurin inhibitor plus methotrexate is routinely used. Early phase studies suggested improved outcomes with Orca-T, an allogeneic T-cell immunotherapy that uses purified donor regulatory T cells to prevent GVHD with significantly less immunosuppression. This phase 3 trial randomized adult patients (N = 187) with acute leukemias or myelodysplastic syndrome undergoing myeloablative conditioning to receive either Orca-T with tacrolimus or a conventional allograft with tacrolimus and methotrexate (Tac/MTX), using granulocyte colony-stimulating factor-mobilized peripheral blood from HLA-matched donors. The primary end point was survival free from moderate-to-severe chronic GVHD (cGVHD; cGFS). Using a stratified log-rank test, cGFS was significantly higher in the Orca-T arm than in Tac/MTX (hazard ratio, 0.26; 95% confidence interval, 0.14-0.47; P< .001). One-year estimates were as follows: cGFS was 78.0% with Orca-T vs 38.4% with Tac/MTX; cumulative incidence of moderate-to-severe cGVHD was 12.6% with Orca-T and 44.0% with Tac/MTX (Gray test P< .001); overall survival was 93.9% with Orca-T vs 83.1% with Tac/MTX (P = .12); GVHD-free and relapse-free survival was 63.1% and 30.9% in the Orca-T and Tac/MTX arms (P< .001), respectively; nonrelapse mortality (NRM) was 3.4% with Orca-T vs 13.2% with Tac/MTX (P = .03). Orca-T met the primary end point of improved survival free from cGVHD compared with Tac/MTX prophylaxis and should be considered a new therapeutic option with low toxicity for GVHD prophylaxis. Moreover, significantly less toxicity was observed with Orca-T patients, including fewer serious infectious complications and less NRM. This trial was registered at www.clinicaltrials.gov as NCT05316701.

BloodVol. 147(11)
City Of Hope National Medical Center (US), Cleveland Clinic (US), Memorial Sloan Kettering Cancer Center (US), University of Miami (US), Emory University (US), University of California, Los Angeles (US), Oregon Health & Science University (US), Cornell University (US), University of Michigan (US), Huntsman Cancer Institute (US), Moffitt Cancer Center (US), University of Chicago (US), Massachusetts General Hospital (US), Centennial Medical Center (US), Menlo School (US), Sarah Cannon (US), City of Hope (US), Michigan United (US), Electronic Arts (United States) (US), Meta (United States) (US), Michigan Medicine (US), Stanford Blood Center (US), Colorado Blood Cancer Institute (US), Global Cancer Institute (US), Stanford Medicine (US), Sylvester Comprehensive Cancer Center (US), Weill Cornell Medicine (US), University of Oklahoma Health Sciences Center (US), University of California, Davis (US), Vanderbilt University Medical Center (US), Stanford University (US)
Amgen, Pfizer, AstraZeneca, Sanofi, Gilead Sciences, American Society of Clinical Oncology, Alexion Pharmaceuticals, University of Pennsylvania, CSL Behring, Ironwood Pharmaceuticals, Incorporated, Jazz Pharmaceuticals, National Comprehensive Cancer Network, Atara Biotherapeutics, CareDx, Incyte, Syndax Pharmaceuticals, Seagen, Novo Nordisk, Kite Pharma
Openalex Percentile: Top 2%
Hematopoietic Stem Cell Transplantation
8.85
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