Patients with acute myeloid leukaemia (AML) receiving allogeneic haematopoietic stem-cell transplantation (allo-HSCT) have a high risk of relapse. The results of a phase I study now published reveal that the infusion of T cells selected for the expression of T cell receptor (TCR) targeting a protein overexpressed in AML cells dramatically reduces the risk of relapse.
Aude Chapuis and collaborators screened CD8+ T cell clones from haematopoietic stem-cell donors to identify cells expressing a high-affinity TCR specific for WT1, a transcription factor that is overexpressed in AML cells. These cells, referred to as TTCR-C4, were expanded and their anti-tumour activity was assessed ex vivo. Subsequently, 12 patients with AML deemed at high risk of relapse but with no evaluable disease 28 days after allo-HSCT received at least one infusion of TTCR-C4 cells; 7 patients received a second infusion 21–797 days after the first one.
At a median follow-up duration of 44 months after the first infusion, all patients remained alive, none of them with detectable disease in bone marrow. A comparator group included 88 patients who had concurrently undergone allo-HSCT at the same institution all of whom had no detectable disease 28 days after; relapse-free survival at the same time point in this group was 45%. The 3-year estimates of overall survival, relapse and non-relapse mortality were 100%, 0% and 0% versus 60%, 28% and 18%, respectively, in patients receiving TTCR-C4 cells versus those in the comparator group (P ≤ 0.01 for all comparisons).
Infusions were generally well tolerated. The number of patients with grade 1–2 graft-versus-host-disease (GVHD) before and after receiving TTCR-C4 cells was 9 (in both cases); 1 patient had grade 3 acute GVHD 97 days after the infusion. The difference in the reported incidence of chronic GVHD between groups was not statistically significant (HR 0.78; P = 0.57). Taken together, the efficacy and safety results indicate that this T cell transfer approach should be tested in studies with larger cohorts of patients.
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Chapuis, A. G. et al. T cell receptor gene therapy targeting WT1 prevents acute myeloid leukemia relapse post-transplant. Nat. Med. 25, 1064–1072 (2019)
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Romero, D. T cell transfer after allo-HSCT in AML. Nat Rev Clin Oncol 16, 528 (2019). https://doi.org/10.1038/s41571-019-0251-z
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DOI: https://doi.org/10.1038/s41571-019-0251-z
