Persistence of ex vivo expanded tumour and pathogen specific T-cells after allogeneic stem cell transplant for myeloid malignancies (the INTACT study)

Abstract Disease relapse and infections cause significant morbidity and mortality post-allogeneic stem cell transplant (HSCT), which remains the only cure for many myeloid malignancies. We investigated a novel combination of donor-derived, tumour-associated, antigen-specific T-cells targeting Wilm’s tumour 1 (WT1) and preferentially expressed antigen in melanoma (PRAME), and multipathogen T-cells targeting CMV, EBV, Adenovirus and Aspergillus given prophylactically post-HSCT. Ten patients with acute myeloid leukaemia (n=6) or high risk myelodysplasia (n=4) who overexpressed WT1 and/or PRAME on diagnostic tumour samples received 1 infusion of multipathogen and 1-4 infusions of tumour-specific T-cells (all at 2x10 7 cells/m 2 ). There were no infusion-related severe adverse events. Low level viral reactivations occurred (CMV n=5, EBV n=7, Adenovirus n=1), however none required treatment. There were no cases of viral tissue disease or invasive fungal infections. At a median 2 years post-transplant, overall survival was 80%, all surviving patients were in complete remission and 6/8 patients had ECOG 0/1. Acute GVHD occurred in 2/10 patients, chronic GVHD in another 2/10. Infusion was associated with rapid, sustained reconstitution of pathogen- and tumour-specific immunity as measured by MHC tetramer for CMV and T-cell receptor based clone tracking. This novel combination of T-cell therapies was safe and associated with excellent clinical outcomes.