Myelodysplastic syndromes (MDS) involve clonal hematopoiesis and cellular dysplasia, driven by genetic and epigenetic alterations. Spliceosome mutations and epigenetic dysregulation underscore the intricate pathogenesis of MDS. The bone marrow microenvironment, stromal dysfunction, chronic inflammation, and immune dysregulation contribute to disease progression. This complex pathogenesis underscores the necessity for targeted therapies, offering a personalized medicine approach, particularly in lower-risk patients. The development of risk scores such as the International Prognostic Scoring System (IPSS), its revision (IPSS-R), and the incorporation of molecular genetics into the IPSS-M have refined the diagnostic and prognostic framework of MDS. These scoring systems facilitate tailored treatment strategies and better prognostication, especially for lower-risk MDS patients. The progression from IPSS to IPSS-R and now to IPSS-M epitomizes the shift towards personalized medicine in the management of MDS. In this review we discuss recent developments and positive phase III studies in lower-risk MDS. The review concludes by proposing a treatment algorithm for lower-risk MDS and highlighting ongoing trials in this heterogeneous population of patients.
