1 research outputs found
Phase II trial of hypomethylating agent combined with nivolumab for acute myeloid leukaemia relapse after allogeneic haematopoietic cell transplantationâImmune signature correlates with response
SummaryAcute myeloid leukaemia (AML) relapse after allogeneic haematopoietic cell transplantation (alloâHCT) is often driven by immuneârelated mechanisms and associated with poor prognosis. Immune checkpoint inhibitors combined with hypomethylating agents (HMA) may restore or enhance the graftâversusâleukaemia effect. Still, data about using this combination regimen after alloâHCT are limited. We conducted a prospective, phase II, openâlabel, singleâarm study in which we treated patients with haematological AML relapse after alloâHCT with HMA plus the antiâPDâ1 antibody nivolumab. The response was correlated with DNAâ, RNAâ and proteinâbased singleâcell technology assessments to identify biomarkers associated with therapeutic efficacy. Sixteen patients received a median number of 2 (range 1â7) nivolumab applications. The overall response rate (CR/PR) at day 42 was 25%, and another 25% of the patients achieved stable disease. The median overall survival was 15.6âmonths. Highâparametric cytometry documented a higher frequency of activated (ICOS, HLAâDR), low senescence (KLRG1, CD57) CD8 effector T cells in responders. We confirmed these findings in a preclinical model. Singleâcell transcriptomics revealed a proâinflammatory rewiring of the expression profile of T and myeloid cells in responders. In summary, the study indicates that the postâalloâHCT HMA/nivolumab combination induces antiâAML immune responses in selected patients and could be considered as a bridging approach to a second alloâHCT. Trialâregistration: EudraCTâNo. 2017â002194â18