Immune checkpoint inhibitors in acute myeloid leukemia

Understanding the immune biology of AML and designing rational approaches to target or harness the immune environment to improve outcomes is an area of intense research in AML. There are two primary immune checkpoint harnessing modalities under clinical evaluation in AML: T-cell (such as PD1 inhibitors nivolumab and pembrolizumab) and macrophage (such as the anti-CD47 antibody magrolimab) These work synergistically with hypomethylating agents. Patients who do not achieve complete or partial responses based on IWG criteria often achieve durable stable disease or hematologic improvement, which may provide meaningful benefit for patients, even in the absence of traditional response unlike cytotoxic therapies. Patients should ideally be prospectively selected for CPI based therapies based on pre-treatment biomarkers, as there are definite populations that are more likely to respond. Immune toxicities are often mistaken for infection or other adverse event; however, if identified and treated early and aggressively with steroids, immune toxicity outcomes can be improved. Therefore, in the formative stage of development ideally only centers with experience in immune therapies should perform CPI studies in AML.