Orca-T vs allogeneic hematopoietic stem cell transplantation (Precision-T): a multicenter, randomized phase 3 trial
Abstract
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.
Article Details
Authors (26)
Everett H. Meyer
1Division of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University, Stanford, CA
Amandeep Salhotra
2Division of Leukemia, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope, Duarte, CA
Arpita P. Gandhi
3Center for Hematologic Malignancies, Knight Cancer Institute, Oregon Health and Science University, Portland, OR
Jeremy Pantin
4Sarah Cannon Transplant and Cellular Therapy Program at TriStar Centennial Medical Center, HCA Healthcare, Nashville, TN
Sagar S. Patel
15Huntsman Cancer Institute, The University of Utah, Salt Lake City, UT
Rasmus T. Hoeg
34Division of Malignant Hematology/Cellular Therapy and Transplantation, Department of Internal Medicine, University of California Davis, Sacramento, CA
Alexandra Gomez-Arteaga
7Weill Cornell Medicine, New York, NY
Rawan Faramand
24Moffitt Cancer Center and Research Institute, Tampa, FL
Roni Tamari
9Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
Edmund K. Waller
Satyajit Kosuri
11Division of Hematology and Oncology, University of Chicago Medicine, Chicago, IL
Antonio M. Jimenez Jimenez
12Division of Transplantation and Cell Therapy, University of Miami Sylvester Comprehensive Cancer Center, Miami, FL
Jennifer Holter-Chakrabarty
13Transplant & Cellular Therapy Clinic, OU Health Stephenson Cancer Center, Oklahoma City, OK
Bhagirathbhai Dholaria
Yi-Bin Chen
1Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA
Betty K. Hamilton
16Blood and Marrow Transplant Program, Cleveland Clinic, Cleveland, OH
John Magenau
University of Michigan
Alireza Eghtedar
18Colorado Blood Cancer Institute, HCA HealthONE Presbyterian St. Luke's, Denver, CO
Joshua M. Murray
19Orca Bio, Menlo Park, CA
Anna Pavlova
Nathaniel B. Fernhoff
19Orca Bio, Menlo Park, CA
James Scott McClellan
19Orca Bio, Menlo Park, CA
M. Scott Killian
19Orca Bio, Menlo Park, CA
Ai Li
Robert S. Negrin
Stanford University Medical Center, Stanford, California, United States
Caspian Oliai