Abstract
Myelodysplastic syndromes (MDS) are a heterogeneous group of diseases characterized by ineffective hematopoiesis and a wide spectrum of manifestations ranging from indolent and asymptomatic cytopenias to acute myeloid leukemia (AML). MDS result from genetic and epigenetic derangements in clonal cells and their surrounding microenvironments. Studies have shown associations between MDS and other autoimmune diseases. Several immune mechanisms have been identified in MDS, suggesting that immune dysregulation might be at least partially implicated in its pathogenesis. This has led to rigorous investigations on the role of immunomodulatory drugs as potential treatment options. Epigenetic modification via immune check point inhibition, while well established as a treatment method for advanced solid tumors, is a new approach being considered in hematologic malignancies including high risk MDS. Several trials are looking at the efficacy of these agents in MDS, as frontline therapy and in relapse, both as monotherapy and in combination with other drugs. In this review, we explore the utility of immune checkpoint inhibitors in MDS and current research evaluating their efficacy.
Highlights
Myelodysplastic syndromes (MDS) are a complex set of diseases characterized by ineffective hematopoiesis and a wide spectrum of manifestations, ranging from indolent and asymptomatic cytopenias to acute myeloid leukemia (AML)
Low risk MDS patients remain stable for years with a 4-year survival rate of 80%, whereas high risk MDS is associated with poor outcomes and rapid progression to leukemia with a median survival of less than a year [2]
Another mechanism by which hypomethylating agents (HMA) increase the sensitivity to PD1/programmed death ligand 1 (PD-L1) inhibition is through the suppression of myeloidderived suppressor cells (MDSCs) in the bone marrow [48]
Summary
Myelodysplastic syndromes (MDS) are a complex set of diseases characterized by ineffective hematopoiesis and a wide spectrum of manifestations, ranging from indolent and asymptomatic cytopenias to acute myeloid leukemia (AML). Low risk MDS patients remain stable for years with a 4-year survival rate of 80%, whereas high risk MDS is associated with poor outcomes and rapid progression to leukemia with a median survival of less than a year [2]. Standard of care in MDS includes supportive care with blood transfusions, hematopoietic growth factors, immune modulation with lenalidomide in del(5q), and epigenetic modulation by hypomethylating agents (HMA) such as azacitidine and decitabine. Azacitidine in particular has been associated with an increase in overall survival [4]. Response to these agents can be lost over time, which emphasizes the importance of gaining a deeper understanding of the disease pathogenesis and development of novel therapies
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