The Association between Immune Checkpoint Proteins and Therapy Outcomes in Acute Myeloid Leukaemia Patients

Simple Summary Despite promising results of clinical trials, the use of immune checkpoint inhibitors (ICI) in acute myeloid leukaemia (AML) remains limited. To date, the United States Food and Drug Administration (FDA) has approved two PD-1 inhibitors, namely nivolumab and pembrolizumab, for treating relapsed/refractory classical Hodgkin lymphoma, and pembrolizumab in primary mediastinal large B-cell lymphoma. In AML, the potential of ICM inhibitors, namely PD-1, PD-L1, and CTLA-4 blockers, was confirmed in clinical trials in relapsed or refractory disease or in high-risk patients. However, the response rate varied widely, possibly due to the heterogeneity of the ICM expression level within different AML cases. Flow cytometric analysis was used for analysing PD-1, PD-L1, CTLA-4, and B7-H3 in untreated AML patients stratified on the basis of clinical outcome and cytogenetic molecular risk. Here, we demonstrated association of selected ICI in AML patients with their response to therapy and overall survival.Abstract The development of novel drugs with different mechanisms of action has dramatically changed the treatment landscape of AML patients in recent years. Considering a significant dysregulation of the immune system, inhibitors of immune checkpoint (ICI) proteins provide a substantial therapeutic option for those subjects. However, use of ICI in haematological malignancies remains very limited, in contrast to their wide use in solid tumours. Here, we analysed expression patterns of the most promising selected checkpoint-based therapeutic targets in AML patients. Peripheral blood of 72 untreated AML patients was used for flow cytometric analysis. Expression of PD-1, PD-L1, CTLA-4, and B7-H3 was assessed within CD4+ (Th) lymphocytes and CD33+ blast cells. Patients were stratified based on therapy outcome and cytogenetic molecular risk. AML non-responders (NR) showed a higher frequency of PD-1 in Th cells compared to those with complete remission (CR). Reduced blast cell level of CTLA-4 was another factor differentiating CR from NR subjects. Elevated levels of PD-1 were associated with a trend for poorer patients' survival. Additionally, prognosis for AML patients was worse in case of a higher frequency of B7-H3 in Th lymphocytes. In summary, we showed the significance of selected ICI as outcome predictors in AML management. Further, multicentre studies are required for validation of those data.