Novel Therapies in Myelodysplastic Syndrome

Abstract Myelodysplastic syndromes (MDSs) are a heterogeneous group of clonal hematopoietic stem cell disorders with treatment approaches tailored to the presence of cytopenias, disease risk, and molecular mutation profile. In higher-risk MDSs, the standard of care are DNA methyltransferase inhibitors, otherwise referred to as hypomethylating agents (HMAs), with consideration for allogeneic hematopoietic stem cell transplantation in appropriate candidates. Given modest complete remission rates (15%–20%) with HMA monotherapy and median overall survival of approximately 18 months, there is much interest in the investigation of combination and targeted treatment approaches. Furthermore, there is no standard treatment approach in patients with progression of disease after HMA therapy. In this review, we aim to summarize the current evidence for the B-cell lymphoma-2 inhibitor, venetoclax, and a variety of isocitrate dehydrogenase inhibitors in the treatment of MDSs along with discussing their potential role in the treatment paradigm of this disease.