Rami Komrokji, MD, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, outlines novel agents under investigation for the treatment of higher-risk myelodysplastic syndromes (MDS), including targeting p53 mutations with APR346 in combination with azacitidine as well as magrolimab, a CD47 inhibitor and pevonedistat, a selective NEDD8 inhibitor. Furthermore, Dr Komrokji discusses latest updates for patients who have failed hypomethylating therapies, including using venetoclax for this indication. This interview was recorded via an online conference call with The Video Journal of Hematological Oncology (VJHemOnc).