TY - JOUR
T1 - Immune checkpoint inhibitors in aml-a new frontier
AU - Thummalapalli, Rohit
AU - Knaus, Hanna A.
AU - Gojo, Ivana
AU - Zeidner, Joshua F.
N1 - Funding Information:
IG has received research funding from Amgen, Am-phivena, and Merck. JFZ has received honoraria from AbbVie, Agios, Celgene, Daiichi Sankyo, Genentech, Pfizer, and Takeda, has served as a consultant for AsystBio Laboratories, Celgene and Takeda, and has received research funding from AROG, Celgene, Forty Seven, Merck, Takeda, and Tolero Pharmaceuticals.
Publisher Copyright:
© 2020 Bentham Science Publishers.
PY - 2020
Y1 - 2020
N2 - Despite recent therapeutic advancements, acute myeloid leukemia (AML) remains a chal-lenging 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 dis-ease 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.
AB - Despite recent therapeutic advancements, acute myeloid leukemia (AML) remains a chal-lenging 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 dis-ease 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.
KW - Acute myeloid leukemia
KW - Immune checkpoint inhibition
KW - PD-1
KW - PD-L1
KW - Stem cell trans-plantation
KW - T cell-mediated immunity
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U2 - 10.2174/1568009620666200421081455
DO - 10.2174/1568009620666200421081455
M3 - Review article
C2 - 32316893
AN - SCOPUS:85089713013
SN - 1568-0096
VL - 20
SP - 545
EP - 557
JO - Current Cancer Drug Targets
JF - Current Cancer Drug Targets
IS - 7
ER -