Current challenges and unmet medical needs in myelodysplastic syndromes

Abstract

Myelodysplastic syndromes (MDS) represent a heterogeneous group of myeloid neoplasms that are characterized by ineffective hematopoiesis, variable cytopenias, and a risk of progression to acute myeloid leukemia. Most patients with MDS are affected by anemia and anemia-related symptoms, which negatively impact their quality of life. While many patients with MDS have lower-risk disease and are managed by existing treatments, there currently is no clear standard of care for many patients. For patients with higher-risk disease, the treatment priority is changing the natural history of the disease by delaying disease progression to acute myeloid leukemia and improving overall survival. However, existing treatments for MDS are generally not curative and many patients experience relapse or resistance to first-line treatment. Thus, there remains an unmet need for new, more effective but tolerable strategies to manage MDS. Recent advances in molecular diagnostics have improved our understanding of the pathogenesis of MDS, and it is becoming clear that the diverse nature of genetic abnormalities that drive MDS demands a complex and personalized treatment approach. This review will discuss some of the challenges related to the current MDS treatment landscape, as well as new approaches currently in development.

Fig. 1. Guideline-recommended treatment options for MDS [41].

A Symptomatic low-risk MDS. B High-risk MDS. ^aNot presently approved. ^bIntensified disease surveillance. ^cThese could be IDH or FLT3 inhibitors (not presently approved). ^dConsider posttransplant disease surveillance strategies. ATG antithymocyte globulin, BSC best supportive care, CsA cyclosporine, CTx chemotherapy, ESA erythropoiesis-stimulating agent, G-CSF granulocyte colony-stimulating factor, HCT hematopoietic cell transplantation, HMA hypomethylating agent, IC induction chemotherapy, LEN lenalidomide, LUSP luspatercept, MDS myelodysplastic syndromes, RBC-TD red blood cell transfusion dependence, RS ring sideroblast, sAML secondary acute myeloid leukemia, sEPO serum erythropoietin, TPO-RA thrombopoietin receptor agonist. This research was originally published in Blood; both figures have been adapted from the original publication. U Platzbecker. Treatment of MDS. Blood. 2019;133:1096-1107. © the American Society of Hematology.