Introduction: 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.
Areas covered: 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.
Expert opinion: 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.
Keywords: MDS biology; Myelodysplastic syndromes; mechanisms; novel agents; targeted therapies.
MDS are rare bone marrow cancers that lead to low blood counts and carry the risk of disease progression to acute myeloid leukemia. The disease risk (lower vs higher) determines the treatment approach. For lower-risk MDS, the focus has been to improve blood counts and patients’ quality of life. Novel treatment strategies are moving earlier in the course of disease to perhaps delay progression. In higher-risk MDS, the goal is to prolong survival and delay progression to acute leukemia. Multiple advanced-phase clinical trials are ongoing to evaluate agents in combination with azacitidine that have shown encouraging results in earlier-phase studies.