Immune Checkpoint Inhibition in Acute Myeloid Leukemia and Myelodysplastic Syndromes

• Published in: Cells (Basel, Switzerland) Vol. 11; no. 14; p. 2249
• Main Authors: Abaza, Yasmin, Zeidan, Amer M
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 20.07.2022; MDPI
• Subjects: Acute myeloid leukemia; Antigens; Azacitidine - therapeutic use; Bone marrow; Cancer therapies; CD47; Chemotherapy; Clinical trials; CTLA-4 protein; Cytotoxicity; Graft versus host disease; Humans; Immune checkpoint; Immune Checkpoint Inhibitors; Immune system; Immunoglobulins; Immunologic Factors - therapeutic use; Leukemia; Leukemia, Myeloid, Acute - pathology; Ligands; Lymphocytes; Lymphocytes T; Medical prognosis; Monoclonal antibodies; Myelodysplastic syndrome; myelodysplastic syndromes; Myelodysplastic Syndromes - drug therapy; Myelodysplastic Syndromes - pathology; Patients; PD-1 protein; Remission (Medicine); Review; Solid tumors; TIM-3; Tumors; CD47; immune checkpoint inhibitors; acute myeloid leukemia; TIM-3; myelodysplastic syndromes
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells11142249

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of many solid tumors, with limited progress made in the area of myeloid malignancies. The low mutational burden of acute myeloid leukemia (AML) is one potential reason behind the lack of activity of T-cell harnessing ICIs, particularly CTLA-4 and PD-1 inhibitors. Innate immune checkpoints play a critical role in the immune escape of AML and myelodysplastic syndromes (MDS). The CD47 targeting agent, magrolimab, has shown promising activity when combined with azacitidine in early phase trials conducted in AML and higher-risk MDS, especially among patients harboring a mutation. Similarly, sabatolimab (an anti-TIM-3 monoclonal antibody) plus hypomethylating agents have shown durable responses in higher-risk MDS and AML in early clinical trials. Randomized trials are currently ongoing to confirm the efficacy of these agents. In this review, we will present the current progress and future directions of immune checkpoint inhibition in AML and MDS.