Immune Checkpoint Inhibition in Myeloid Malignancies: Moving Beyond the PD-1/PD-L1 and CTLA-4 Pathways

Immune checkpoint inhibitors (ICI) have yielded mixed but largely underwhelming results in clinical trials in patients with acute myeloid leukemia and myelodysplastic syndromes to date. However, increasing understanding of the immunologic landscape, potential biomarkers for benefits, and mechanisms of resistance, as well as the use of rational combinations, and identification of novel targets leaves plenty of room for optimism. Herein, we review recent advances in the preclinical and clinical development of ICI therapy in patients with myeloid malignancies and explore some of the important challenges facing the field such as the absence of validated biomarkers, the development of synergistic and safe combination therapies, and efforts to determine the best setting of ICI along the disease course. We finally foresee the future of the field and propose solutions to some of the major beforementioned obstacles.