TY - JOUR
T1 - Outcome of donor-derived TAA-T cell therapy in patients with high-risk or relapsed acute leukemia post allogeneic BMT
AU - Kinoshita, Hannah
AU - Cooke, Kenneth R.
AU - Grant, Melanie
AU - Stanojevic, Maja
AU - Cruz, C. Russell
AU - Keller, Michael
AU - Fortiz, Maria Fernanda
AU - Hoq, Fahmida
AU - Lang, Haili
AU - Barrett, A. John
AU - Liang, Hua
AU - Tanna, Jay
AU - Zhang, Nan
AU - Shibli, Abeer
AU - Datar, Anushree
AU - Fulton, Kenneth
AU - Kukadiya, Divyesh
AU - Zhang, Anqing
AU - Williams, Kirsten M.
AU - Dave, Hema
AU - Dome, Jeffrey S.
AU - Jacobsohn, David
AU - Hanley, Patrick J.
AU - Jones, Richard J.
AU - Bollard, Catherine M.
N1 - Funding Information:
This work was supported by National Cancer Institute (NCI), National Institutes of Health (NIH), grant P01-CA-015396 (R.J.J., C.M.B., and K.R.C.), a Leukemia and Lymphoma Society SCOR 7018-04 (C.M.B., K.M.W. and P.J.H.), a Hyundai Hope on Wheels grant (C.M.B. and K.M.W.), Ben’s Run Foundation (C.M.B. and K.M.W.), Rising Tides Foundation (K.M.W. and C.M.B.), and a Ruth L. Kirschstein National Research Service Award Institutional Research Training Grant awarded to the Children’s Research Institute Hematology Training Program by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (5T32HL110841-08) (H.K.). This project was supported by a grant from the NIH National Center for Advancing Translational Sciences (UL1TR001876).
Publisher Copyright:
© 2022 by The American Society of Hematology.
PY - 2022/4/26
Y1 - 2022/4/26
N2 - Patients with hematologic malignancies relapsing after allogeneic blood or marrow transplantation (BMT) have limited response to conventional salvage therapies, with an expected 1-year overall survival (OS) of,20%. We evaluated the safety and clinical outcomes following administration of a novel T-cell therapeutic targeting 3 tumor-associated antigens (TAA-T) in patients with acute leukemia who relapsed or were at high risk of relapse after allogeneic BMT. Lymphocytes obtained from the BMT donor were manufactured to target TAAs WT1, PRAME, and survivin, which are over-expressed and immunogenic in most hematologic malignancies. Patients received TAA-T infusions at doses of 0.5 to 4 3 107/m2. Twenty-three BMT recipients with relapsed/refractory (n 5 11) and/or high-risk (n 5 12) acute myeloid leukemia (n 5 20) and acute lymphoblastic leukemia (n 5 3) were infused posttransplant. No patient developed cytokine-release syndrome or neurotoxicity, and only 1 patient developed grade 3 graft-versus-host disease. Of the patients who relapsed post-BMT and received bridging therapy, the majority (n 5 9/11) achieved complete hematologic remission before receiving TAA-T. Relapsed patients exhibited a 1-year OS of 36% and 1-year leukemia-free survival of 27.3% post–TAA-T. The poorest prognosis patients (relapsed,6 months after transplant) exhibited a 1-year OS of 42.8% postrelapse (n 5 7). Median survival was not reached for high-risk patients who received preemptive TAA-T posttransplant (n 5 12). Although as a phase 1 study, concomitant antileukemic therapy was allowed, TAA-T were safe and well tolerated, and sustained remissions in high-risk and relapsed patients were observed. Moreover, adoptively transferred TAA-T detected by T-cell receptor V-b sequencing persisted up to at least 1 year postinfusion. This trial was registered at clinicaltrials.gov as #NCT02203903.
AB - Patients with hematologic malignancies relapsing after allogeneic blood or marrow transplantation (BMT) have limited response to conventional salvage therapies, with an expected 1-year overall survival (OS) of,20%. We evaluated the safety and clinical outcomes following administration of a novel T-cell therapeutic targeting 3 tumor-associated antigens (TAA-T) in patients with acute leukemia who relapsed or were at high risk of relapse after allogeneic BMT. Lymphocytes obtained from the BMT donor were manufactured to target TAAs WT1, PRAME, and survivin, which are over-expressed and immunogenic in most hematologic malignancies. Patients received TAA-T infusions at doses of 0.5 to 4 3 107/m2. Twenty-three BMT recipients with relapsed/refractory (n 5 11) and/or high-risk (n 5 12) acute myeloid leukemia (n 5 20) and acute lymphoblastic leukemia (n 5 3) were infused posttransplant. No patient developed cytokine-release syndrome or neurotoxicity, and only 1 patient developed grade 3 graft-versus-host disease. Of the patients who relapsed post-BMT and received bridging therapy, the majority (n 5 9/11) achieved complete hematologic remission before receiving TAA-T. Relapsed patients exhibited a 1-year OS of 36% and 1-year leukemia-free survival of 27.3% post–TAA-T. The poorest prognosis patients (relapsed,6 months after transplant) exhibited a 1-year OS of 42.8% postrelapse (n 5 7). Median survival was not reached for high-risk patients who received preemptive TAA-T posttransplant (n 5 12). Although as a phase 1 study, concomitant antileukemic therapy was allowed, TAA-T were safe and well tolerated, and sustained remissions in high-risk and relapsed patients were observed. Moreover, adoptively transferred TAA-T detected by T-cell receptor V-b sequencing persisted up to at least 1 year postinfusion. This trial was registered at clinicaltrials.gov as #NCT02203903.
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U2 - 10.1182/bloodadvances.2021006831
DO - 10.1182/bloodadvances.2021006831
M3 - Article
C2 - 35244681
AN - SCOPUS:85129235961
SN - 2473-9529
VL - 6
SP - 2520
EP - 2534
JO - Blood advances
JF - Blood advances
IS - 8
ER -