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2338 Donor-Derived T-Cells Specific for WT1 and PRAME in Combination with T-Cells Specific for Multiple Pathogens for Prevention of Relapse and Infection after Haemopoietic Stem Cell Transplant (HSCT) for Acute Myeloid Leukaemia (AML) or High-Risk Myelodysplasia (MDS) - (The INTACT Trial)Clinically Relevant Abstract

Program: Oral and Poster Abstracts
Session: 703. Adoptive Immunotherapy: Mechanisms and New Approaches: Poster II
Hematology Disease Topics & Pathways:
Biological, AML, Diseases, Therapies, MDS, immunotherapy, Myeloid Malignancies, transplantation
Sunday, December 6, 2020, 7:00 AM-3:30 PM

Wei Jiang, MBBS, M Clin Med, FRACP, FRCPA1, Emily Blyth, B. Med(Hons), FRACP, FRCPA, PhD2,3,4*, Peter J. Shaw, MA, FRACP5, Leighton Edward Clancy, BSc, PhD4*, Kenneth P. Micklethwaite, MBBS, PhD, FRACP, FRCPA4,6,7*, Abir Bhattacharyya, MBBS, FRACP, FRCPA8*, Elissa Atkins, RN9*, Selmir Avdic, PhD10*, Gaurav Sutrave, MBBS, FRACP, FRCPA11*, Janine Street, BSc MSc (Hons)12* and David Gottlieb, MBBS, MD, FRACP, FRCPA7*

1Westmead Institute of Medical Research, Westmead, NSW, Australia
2Westmead Hospital, Blood and Marrow Transplant Unit, Sydney, Australia
3Westmead Institute for Medical Research, University of Sydney, Sydney, Australia
4Westmead Hospital, Sydney Cellular Therapies Laboratory, Sydney, Australia
5The Children's Hospital at Westmead, The Sydney Children's Hospitals Network, Westmead, Australia
6University of Sydney, Sydney, NSW, Australia
7Department of Haematology and Bone Marrow Transplantation, Westmead Hospital, Sydney, NSW, Australia
8Dept of Haematology, Westmead Hospital, Sydney, NSW, Australia
9Westmead Hospital, Westmead, Australia
10Westmead Institute for Medical Research, Sydney, Australia
11Westmead Institute of Medical Research, Sydney, AUS
12Westmead Institute of Medical Research, Sydney, Australia


Disease relapse and infection cause significant morbidity and mortality after allogeneic HSCT for AML and MDS. Wilms’ tumour 1 (WT1) and preferentially expressed antigen in melanoma (PRAME) are both commonly overexpressed in these conditions, and are attractive targets for immunotherapy. We have assessed the safety of a novel combination of tumour associated antigen (TAA) specific and multipathogen (MP) specific T cells administered prophylactically after HSCT in a phase 1 trial.


Patients were eligible for the study if WT1 or PRAME gene expression was elevated as determined by droplet digital PCR on diagnostic tumour samples. TAA and MP specific T cells were generated from stem cell donors by stimulating apheresis-derived mononuclear cells with autologous antigen presenting cells expressing tumour, viral or fungal antigens. T cells specific for CMV, EBV and Aspergillus antigens were produced separately and pooled in equal parts into a MP product. Patients received 1 infusion of MP specific T cells and up to 4 infusions of TAA specific T cells at 4-weekly intervals dosed at 2x107/m2, from 28 days post HSCT.


Seven HSCT recipients have received a total of 26 T cell infusions to date. Median age was 49 years (range 26-67), disease AML (n=4) or high risk MDS (n=3), conditioning myeloablative (n=6) or reduced-intensity (n=1), donor source sibling (n=4) or matched unrelated (n=3). Median expression of WT1 on diagnostic bone marrow tissue was 1464 copies/104 copies of ABL (0-3870), PRAME 131 copies/104 copies of ABL (4-1670). Mean tumour antigen specificity in the TAA product was 2.2% of CD3+ cells for WT1 and 7.3% of CD4+ cells for PRAME. Mean total pathogen specificity in the MP product was approximately 15% (CMV=4.7% and EBV=5.4% of CD3+ cells, Aspergillus=5.3% of CD4+ cells). Patients received WT1 specific (n=3), PRAME specific (n=3) or both WT1 and PRAME specific T cells (n=1). All patients received MP specific T cells. No immediate infusion-related adverse events were reported. At the time of report, at a median of 375 days post-transplant (80-847), 5 out of 7 patients remain alive. Four patients remain in complete disease remission without graft versus host disease (GVHD). One patient did not proceed after 3 of 5 planned infusions after developing chronic lung GVHD but remains in disease remission. There have been 2 deaths (progressive disease and multiorgan failure). The patient with progressive disease had MDS with complex cytogenetics with evidence of persistent disease pre and post-HSCT, prior to T cell infusions. The patient with multiorgan failure had multiple post-transplant complications including bacterial sepsis, hepatic venoocclusive disease and grade 3 acute GVHD of the gut prior to infusion. Patients had low level viral reactivation (CMV n=3, EBV n=5, BKV n=3, HHV6 n=2), however none required treatment and there were no cases of viral tissue disease or EBV post-transplant lymphoproliferative disorder. There were no invasive fungal infections.


Prophylactic infusions of donor derived WT1/PRAME specific and multipathogen specific T cells post HSCT are well-tolerated and associated with low rates of infection and relapse in patients treated to date.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH