Advances in myelodysplastic syndromes: promising novel agents and combination strategies

Myelodysplastic syndromes (MDS) are heterogeneous group of clonal hematopoietic stem cell neoplasms that have limited approved treatment options. Multiple novel agents are currently being tested in a clinical trial setting. From a therapeutic perspective, MDS is generally divided into lower-risk and higher-risk disease. In this review, we summarize some of the most prominent novel agents currently in development.

This review focuses on select clinical trials in both lower- and higher-risk MDS, elucidating the mechanisms of action and rationale for drug combinations and summarizing early safety and efficacy data using novel agents in MDS.

Advances in understanding the innate immune system, telomere biology, as well as genomic drivers of the disease have led to the development of multiple novel agents that are currently in late stages of clinical development in MDS. Imetelstat is being tested in lower-risk disease and the phase III clinical trial recently completed accrual. Magrolimab, sabatolimab, and venetoclax in addition to novel oral hypomethylating agents (HMA) are being investigated in higher-risk MDS. These advances will hopefully bring better treatment options to patients and lead to a shift in the treatment paradigm. Post HMA therapy remains an area of dire unmet need.