Outcome of donor-derived TAA-T cell therapy in patients with high-risk or relapsed acute leukemia post allogeneic BMT

Hannah Kinoshita, Kenneth R. Cooke, Melanie Grant, Maja Stanojevic, C. Russell Cruz, Michael Keller, Maria Fernanda Fortiz, Fahmida Hoq, Haili Lang, A. John Barrett, Hua Liang, Jay Tanna, Nan Zhang, Abeer Shibli, Anushree Datar, Kenneth Fulton, Divyesh Kukadiya, Anqing Zhang, Kirsten M. Williams, Hema DaveJeffrey S. Dome, David Jacobsohn, Patrick J. Hanley, Richard J. Jones, Catherine M. Bollard

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)2520-2534
Number of pages15
JournalBlood Advances
Issue number8
StatePublished - Apr 26 2022

ASJC Scopus subject areas

  • Hematology


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