Novel Treatment Options in Low-risk Myelodysplastic Syndrome

Myelodysplastic syndromes (MDS) are a group of clonal bone marrow disorders driven by ineffective hematopoiesis, genetic mutations, and progressive marrow failure. These underlying disease processes lead to chronic cytopenias, increased infection and bleeding risk, transfusion dependence, and, in some patients, progression to acute myeloid leukemia—significantly impacting both survival and quality of life. Risk stratification plays a central role in guiding management, with tools such as prognostic scoring systems used to categorize patients as lower- or higher-risk based on cytogenetics, marrow blasts, and blood counts. Treatment goals differ across these groups: in lower-risk MDS, the focus is on improving cytopenias, reducing transfusion burden, and maintaining quality of life, while higher-risk disease emphasizes altering disease course, delaying progression to AML, and extending survival.

Before the availability of FDA-approved therapies specifically for low-risk myelodysplastic syndrome (MDS), management was largely focused on supportive care aimed at alleviating symptoms rather than modifying disease course. Treatment strategies primarily addressed cytopenias, particularly anemia, through red blood cell transfusions and, in selected patients, erythropoiesis-stimulating agents. While these approaches improved quality of life and reduced symptom burden, they did not alter the underlying biology of the disease. Supportive care measures such as transfusions offer rapid symptomatic relief but can lead to cumulative complications, including iron overload, transfusion reactions, and increased healthcare utilization. Iron chelation therapy may mitigate iron-related organ damage in transfusion-dependent patients, but its use is limited by tolerability, adherence challenges, and uncertainty around long-term outcomes. Overall, these limitations underscored the unmet need for targeted, disease-directed therapies in low-risk MDS.

Management of anemia in low-risk myelodysplastic syndrome (MDS) has evolved with a clearer understanding of patient selection and therapeutic sequencing.

Luspatercept has become an important option for patients with lower-risk myelodysplastic syndrome who have anemia, but appropriate monitoring and management of adverse effects are essential.

Imetelstat represents a novel, disease-modifying approach for patients with lower-risk myelodysplastic syndromes who have limited options after standard therapies.

The IMerge trial provided important insights into the efficacy of imetelstat across patients with varying serum erythropoietin (sEPO) levels, a clinically relevant factor in low-risk MDS.

These IMerge trial analyses provide important context for understanding both the short- and long-term effects of imetelstat in patients with lower-risk myelodysplastic syndromes (LR-MDS).

Recent data presented at ASH have further clarified the evolving role of erythroid maturation agents in the management of lower-risk myelodysplastic syndromes (MDS).

Oral decitabine/cedazurine represents an important advancement in the management of both high-risk and select low-risk myelodysplastic syndromes (MDS), as well as chronic myelomonocytic leukemia (CMML).