Immune checkpoint inhibition in myeloid malignancies: Moving beyond the PD-1/PD-L1 and CTLA-4 pathways

Blood Rev. 2021 Jan:45:100709. doi: 10.1016/j.blre.2020.100709. Epub 2020 May 23.

Abstract

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.

Keywords: Acute myeloid leukemia; CD47; Immune checkpoint inhibition; Leukemic stem cells; Myelodysplastic syndromes; TIM-3.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • B7-H1 Antigen / antagonists & inhibitors
  • Biomarkers, Tumor
  • CTLA-4 Antigen / antagonists & inhibitors
  • Humans
  • Immune Checkpoint Inhibitors / administration & dosage
  • Immune Checkpoint Inhibitors / adverse effects
  • Immune Checkpoint Inhibitors / therapeutic use*
  • Leukemia, Myeloid, Acute / drug therapy
  • Myeloproliferative Disorders / diagnosis
  • Myeloproliferative Disorders / drug therapy*
  • Myeloproliferative Disorders / etiology
  • Myeloproliferative Disorders / metabolism
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / metabolism
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Signal Transduction / drug effects

Substances

  • Antineoplastic Agents
  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Immune Checkpoint Inhibitors
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor