Objective: To discuss the recent and emerging data for novel targeted therapies in myelodysplastic syndromes (MDS).
Data sources: A literature search from January 2015 to June 2021 was performed using the key terms targeted therapies, myelodysplastic syndromes, DNA repair, erythroid differentiation therapy, epigenetic inhibitors, signal transduction inhibitors, and apoptosis-inducing agents.
Study selection and data extraction: Relevant clinical trials and articles in the English language were identified and reviewed.
Data synthesis: MDS are a heterogeneous group of malignant blood disorders affecting the bone marrow (BM), ultimately leading to BM failure, acute leukemia, and death. Selection of treatment is influenced by the severity of symptoms, cytopenia, cytogenetics, prognostic category, medical fitness, and patient preferences. Although current therapies such as erythropoiesis stimulating agents (ESAs) and hypomethylating agents (HMAs) help improve anemia and reduce transfusion burden, limited treatment options exist when patients experience treatment failure to ESAs or HMA. Recent regulatory approval of luspatercept, which targets the erythroid differentiation pathway, represents a major therapeutic advance in the management of anemia in MDS patients who are refractory to ESAs. Many investigational targeted therapies that aim at the myeloid lineage signaling pathway and the immune microenvironment are in active development.
Relevance to patient care and clinical practice: This nonexhaustive review summarizes and describes the recent data for targeted therapies for MDS.
Conclusion: The development of novel and investigational therapeutic agents continues to contribute to an improved understanding of tumor biology. The precise therapeutic role and timing of these agents remain to be elucidated.
Keywords: biomarkers; epigenetics; immunotherapy; myelodysplastic syndromes; risk prognostication; targeted therapy.