Myelodysplastic syndrome (MDS) management is stratified by risk, and progress has been uneven — real gains in lower-risk anemia, but a series of disappointments in higher-risk disease.
Lower-risk MDS
The goal is to reduce transfusion dependence. Erythropoiesis-stimulating agents remain a starting point, but luspatercept is now a first-line option (superior to epoetin alfa in the COMMANDS trial), and imetelstat (Rytelo), a telomerase inhibitor approved in 2024, helps transfusion-dependent patients who fail ESAs. HIF-prolyl-hydroxylase inhibitors such as roxadustat are being studied for MDS-related anemia.
Higher-risk MDS
Hypomethylating agents — azacitidine and decitabine (including the oral decitabine-cedazuridine combination) — remain the backbone, and allogeneic stem-cell transplantation is still the only potentially curative option. The story of the past few years, however, has been one of failed combinations: several agents once promising as hypomethylating-agent partners did not pan out — the anti-CD47 antibody magrolimab was discontinued after negative trials, and pevonedistat and sabatolimab likewise failed to deliver — so the anticipated leap in higher-risk MDS has not materialized. Venetoclax added to a hypomethylating agent is under active study, and targeted therapy has a defined niche in ivosidenib for IDH1-mutated MDS (approved 2023).
Further reading: MDS review (Sekeres & Taylor, JAMA 2022); luspatercept COMMANDS and imetelstat IMerge; magrolimab ENHANCE program (discontinued); ivosidenib in IDH1-mutated MDS.