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

Hannah Kinoshita, Center for Cancer and Immunology Research, Children's National Research Institute, Children's National Hospital, Washington, DC.
Kenneth R. Cooke, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD.
Melanie Grant, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA.
Maja Stanojevic, Center for Cancer and Immunology Research, Children's National Research Institute, Children's National Hospital, Washington, DC.
C Russell Cruz, Center for Cancer and Immunology Research, Children's National Research Institute, Children's National Hospital, Washington, DC.
Michael Keller, Center for Cancer and Immunology Research, Children's National Research Institute, Children's National Hospital, Washington, DC.
Maria Fernanda Fortiz, Center for Cancer and Immunology Research, Children's National Research Institute, Children's National Hospital, Washington, DC.
Fahmida Hoq, Center for Cancer and Immunology Research, Children's National Research Institute, Children's National Hospital, Washington, DC.
Haili Lang, Center for Cancer and Immunology Research, Children's National Research Institute, Children's National Hospital, Washington, DC.
A John Barrett, Stem Cell Transplantation and Cell Therapy Program, George Washington Cancer Center, Washington, DC.
Hua Liang, Department of Statistics, The George Washington University, Washington, DC; and.
Jay Tanna, Center for Cancer and Immunology Research, Children's National Research Institute, Children's National Hospital, Washington, DC.
Nan Zhang, Center for Cancer and Immunology Research, Children's National Research Institute, Children's National Hospital, Washington, DC.
Abeer Shibli, Center for Cancer and Immunology Research, Children's National Research Institute, Children's National Hospital, Washington, DC.
Anushree Datar, Center for Cancer and Immunology Research, Children's National Research Institute, Children's National Hospital, Washington, DC.
Kenneth Fulton, Center for Cancer and Immunology Research, Children's National Research Institute, Children's National Hospital, Washington, DC.
Divyesh Kukadiya, Center for Cancer and Immunology Research, Children's National Research Institute, Children's National Hospital, Washington, DC.
Anqing Zhang, Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, DC.
Kirsten M. Williams, Department of Pediatric Hematology/Oncology, Aflac Cancer & Blood Disorders Center, Children's Healthcare of Atlanta and Emory University School of Medicine, Atlanta, GA.
Hema Dave, Center for Cancer and Immunology Research, Children's National Research Institute, Children's National Hospital, Washington, DC.
Jeffrey S. Dome, Center for Cancer and Immunology Research, Children's National Research Institute, Children's National Hospital, Washington, DC.
David Jacobsohn, Center for Cancer and Immunology Research, Children's National Research Institute, Children's National Hospital, Washington, DC.
Patrick J. Hanley, Center for Cancer and Immunology Research, Children's National Research Institute, Children's National Hospital, Washington, DC.
Richard J. Jones, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD.
Catherine M. Bollard, Center for Cancer and Immunology Research, Children's National Research Institute, Children's National Hospital, Washington, DC.

Document Type

Journal Article

Publication Date

4-26-2022

Journal

Blood advances

Volume

6

Issue

8

DOI

10.1182/bloodadvances.2021006831

Abstract

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 × 107/m2. Twenty-three BMT recipients with relapsed/refractory (n = 11) and/or high-risk (n = 12) acute myeloid leukemia (n = 20) and acute lymphoblastic leukemia (n = 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 = 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 = 7). Median survival was not reached for high-risk patients who received preemptive TAA-T posttransplant (n = 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-β sequencing persisted up to at least 1 year postinfusion. This trial was registered at clinicaltrials.gov as #NCT02203903.

Department

Pediatrics

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