Title:Immune Checkpoint Inhibitors in AML-A New Frontier
VOLUME: 20 ISSUE: 7
Author(s):Rohit Thummalapalli, Hanna A. Knaus, Ivana Gojo and Joshua F. Zeidner*
Affiliation:Department of Medicine, Johns Hopkins Hospital, Baltimore, MD, Medical University of Vienna, Department of Medicine, Division of Bone Marrow Transplantation and Cellular Therapies, Vienna, Department of Medical Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, University of North Carolina, Lineberger Comprehensive Cancer Center, Chapel Hill, NC
Keywords:Acute myeloid leukemia, immune checkpoint inhibition, PD-1, PD-L1, T cell-mediated immunity, stem cell transplantation.
Abstract:Despite recent therapeutic advancements, acute myeloid leukemia (AML) remains a challenging
clinical entity with overall poor outcomes. Given the evident role of T cell-mediated immunity
in response to allogeneic stem cell transplantation and donor lymphocyte infusions, strategies
that enhance immune activation and mitigate immune dysfunction represent attractive therapeutic
platforms to improve clinical outcomes in AML. Pre-clinical data suggest that immune dysfunction
is a major contributor to AML progression and relapse. Increased expression of immune checkpoints
such as programmed death 1 (PD-1) contributes to AML immune evasion and is associated with disease
progression. Immune checkpoint inhibition is being explored in AML with early evidence of
clinical activity, particularly in combination with cytotoxic chemotherapy and hypomethylating
agents. In this review, we explore the scientific rationale behind the use of immune checkpoint inhibition
either as single agents or in combination with hypomethylating agents or cytotoxic chemotherapy
and provide a clinical update of both completed and ongoing trials in AML.
