New investigational combinations for higher-risk MDS

• DOI: 10.1182/hematology.2022000351
• Publication Date: 2022-12-09T16:11:20Z
• Authors: Kristin L. Koenig; Uma Borate
• Keywords: Leukemia, Myeloid, Acute; 03 medical and health sciences; 0302 clinical medicine; Bone Marrow; Myelodysplastic Syndromes; Azacitidine; Humans; Aged; Stem Cell Transplantation; 3. Good health

Abstract Myelodysplastic syndromes (MDS) are typically a hematologic malignancy of older adults characterized by dysplastic hematopoiesis, cytopenia(s), and risk of acute myeloid leukemia transformation. The treatment approach to MDS depends largely on risk stratification of an individual's disease, most commonly using the Revised International Prognostic Scoring System, which takes into account peripheral blood cytopenias and bone marrow blast percentage and cytogenetics. The current standard of care for patients with higher-risk MDS (HR-MDS) includes hypomethylating agents (HMAs), decitabine and azacitidine, and allogenic stem cell transplant for patients able to undergo this therapy. However, leukemic transformation remains a significant challenge, and outcomes with these current therapies are still dismal. There are several novel therapies in development aiming to improve upon the outcomes of single-agent HMA therapy using combination strategies with HMAs. Here we discuss the current standard of care for HR-MDS treatment and explore some of the most promising combination therapies coming out of the pipeline for HR-MDS.