Emerging Treatments for Myelodysplastic Syndromes: Biological Rationales and Clinical Translation

Authors

Juan Jose Rodriguez-Sevilla
Vera Adema
Guillermo Garcia-Manero
Simona Colla

Publication Date

2-21-2023

Journal

Cell Reports Medicine

Abstract

Myelodysplastic syndromes (MDSs) are a heterogeneous group of clonal hematopoietic stem cell disorders characterized by myeloid dysplasia, peripheral blood cytopenias, and increased risk of progression to acute myeloid leukemia (AML). The standard of care for patients with MDS is hypomethylating agent (HMA)-based therapy; however, nearly 50% of patients have no response to the treatment. Patients with MDS in whom HMA therapy has failed have a dismal prognosis and no approved second-line therapy options, so enrollment in clinical trials of experimental agents represents these patients' only chance for improved outcomes. A better understanding of the molecular and biological mechanisms underpinning MDS pathogenesis has enabled the development of new agents that target molecular alterations, cell death regulators, signaling pathways, and immune regulatory proteins in MDS. Here, we review novel therapies for patients with MDS in whom HMA therapy has failed, with an emphasis on the biological rationale for these therapies' development.

Keywords

myelodysplastic syndromes, hypomethylating agents, secondary acute myeloid leukemia, novel therapeutic agents

Comments

PMID: 36787738