Prospective phase I study of nivolumab to promote graft‐versus‐tumour in relapsed or refractory haematological malignancy post allogeneic haematopoietic stem cell transplantation

Summary 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.