Authors
Trung Q Ngo, Eric Wong, Joanne E Davis, Mandy Ludford-Menting, Jessica Klass, Sara K Dohrmann, Rachel Koldej, David Ritchie
Published in
British journal of haematology. Oct 16, 2026. Epub Oct 16, 2026.
Abstract
Allogeneic haematopoietic stem cell transplantation (alloHSCT) relies on donor-derived T cells to mediate the graft-versus-tumour (GVT) effect, but relapse may result from impaired immune reconstitution, tumour antigen downregulation or T-cell exhaustion. This prospective phase I study evaluated the safety and efficacy of the PD-1 inhibitor, nivolumab, in enhancing GVT post-alloHSCT and explored the impact of baseline T-cell phenotypes on clinical outcomes. Fourteen patients with relapsed/refractory haematological malignancies post-alloHSCT received nivolumab every 2 weeks for up to 48 weeks. Six achieved complete remission, all with chronic lymphoid malignancies. Patients with myeloid malignancies or acute lymphoblastic leukaemia had inferior progression-free survival (4.3 vs. 11.7 months, p < 0.05) and overall survival (43.6 months vs. undefined, p < 0.05) than those with chronic lymphoid malignancies. Nine serious adverse events occurred, including four dose-limiting toxicities due to graft-versus-host disease (GVHD) or pneumonitis. Patients who developed GVHD had higher T-cell activation at baseline and achieved early clinical responses. These findings confirm that nivolumab can promote GVT post-alloHSCT, particularly in lymphoid disorders. Baseline immunophenotype (effector memory T cells, Human Leukocyte Antigen - DR isotype [HLA-DR]) and gene expression (granzyme A [GZMA], granzyme B [GZMB], perforin [PRF1]) can be used as biomarkers to help identify patients most likely to benefit from salvage checkpoint inhibition.
PMID:
42888040
Bibliographic data and abstract were imported from PubMed on 17 Oct 2026.
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