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Expert Rev Anticancer Ther. 2019 May;19(5):393-404. doi: 10.1080/14737140.2019.1589374. Epub 2019 Mar 19.

Immune checkpoint-based therapy in myeloid malignancies: a promise yet to be fulfilled.

Author information

1
a Department of Internal Medicine, Section of Hematology , Yale University School of Medicine , New Haven , CT , USA.
2
b Department of Medicine, Section of Hematologic Oncology , Memorial Sloan Kettering Cancer Center , New York , NY , USA.

Abstract

Immune system evasion is essential for tumor cell survival and is mediated by the immunosuppressive tumor microenvironment and the activation of inhibitory immune checkpoints. While immune checkpoint-based therapy yielded impressive results in several advanced solid malignancies such as melanoma and non-small cell lung cancer, its role in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) is still evolving. Areas covered: Here we review the immunology in the tumor microenvironment in the bone marrow and discuss the current preclinical and clinical data for immune checkpoint-based therapy in myeloid neoplasms. Expert commentary: Clinical trials of immune checkpoint inhibitors (ICI) in AML and MDS are still in early stages and reported results so far have been modest especially for monotherapy use in the refractory settings. However, there are preliminary data for synergistic effects for combination of multiple ICI with hypomethylating agents and conventional chemotherapy. ICI might also be effective in eradicating minimal residual disease and to prevent relapse following induction chemotherapy or hematopoietic stem cell transplant. Additional trials to provide insight into the efficacy and safety profile of immune checkpoint-based therapy, its optimal timing and potential combination with other types of therapy as well as identification of predictive biomarkers are needed.

KEYWORDS:

Acute myeloid leukemia; CTLA-4; PD-1; T-cells; combination therapy; immune checkpoint blockade; tumor immunology

PMID:
30887841
PMCID:
PMC6527485
[Available on 2020-05-01]
DOI:
10.1080/14737140.2019.1589374

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