Low-risk MDS Management May Change as New Technology, Therapies Emerge


A new review article shows how technologies like next-generation sequencing might help clinicians tailor care for myelodysplastic syndromes (MDS).

The expanding number of available therapies and new insights into variables that affect the disease course have made the treatment of patients with low-risk myelodysplastic syndromes (LR-MDS) increasingly nuanced, according to a new review article.

Investigators outlined the latest research and its implications for case management in Blood Cancer Journal.

MDS poses challenges both due to the heterogeneity of hematopoietic stem and progenitor cell disorders included in the disease category and the varying levels of risk associated with individual cases. People with MDS have ineffective hematopoiesis and abnormal blood cell development, which can lead to cytopenias and eventually progress to acute myeloid leukemia (AML).

The disease mostly affects older patients, with a median age at diagnosis of 70, and most patients are considered to be at a low risk of near-term progression to AML, the authors wrote.

“However, the presence of anemia and complications related to cytopenias, transfusions, and inflammation can negatively affect comorbid conditions, potentially reducing the quality of life (QOL) and increasing the mortality of these patients relative to the general population,” they wrote.

In their report, they reviewed the latest research into the disease and its pathogenesis and considered how this might affect patient care. They said that in most low-risk cases, the emphasis should be on improving symptoms and QOL.

“This is usually related to the management of cytopenias, most commonly anemia, and managing sequelae of disease and therapy (eg, iron overload),” they explained. “We, therefore, develop a disease management plan and treatment sequence with this in mind.”

Progressive anemia is a common complication, they said, which eventually leads to a need for red blood cell (RBC) transfusions.

“We administer erythropoiesis-stimulating agents (ESAs), which increase RBC production in the bone marrow, as first-line therapy for patients with LR-MDS and symptomatic anemia,” they said, adding that ESAs cannot cure anemia, and patients will eventually stop responding to therapy.

In some patients, other therapies are considered, such as lenalidomide (Revlimid) for patients with MDS-del(5q).

“Generally, therapies such as lenalidomide have been reserved for transfusion-dependent patients; however, there are ongoing investigations exploring the possible benefits of starting treatments prior to transfusion dependence,” the investigators said.

There is less consensus about treatment options for people with non-del(5q) MDS, they said.

Key to making treatment decisions for patients is assessing their response to therapy. The investigators noted that durable achievement of hematologic response and/or RBC-transfusion independence have historically been seen as key indicators of treatment response, but they said it is increasingly understood that response expectations should be shaped by disease burden at the time therapy is initiated. In addition, they said newer technology allows for more precise evaluation of patients.

“Identification of somatic gene mutations and establishment of comprehensive mutational profiles of MDS samples using next-generation sequencing (NGS) plays a growing role in the diagnosis, prognosis, treatment selection, and monitoring of MDS,” they said.

Several new therapies have also been investigated for MDS, including imetelstat, a competitive inhibitor of telomerase enzymatic activity, and roxadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor.

As more therapies become available, the study authors said optimal selection of therapies and treatment sequences is becoming more relevant.

“In the future, mutational profiles may be incorporated into risk stratification schemes and treatment algorithms, resulting in a more targeted treatment approach,” they wrote.

Still, the investigators lamented that progress in treating MDS has been slow. The number of clinical trials of MDS therapies has been relatively small, and many phase 1 trials of potential MDS therapies are aimed at other cancers and merely include patients with MDS as a patient subgroup.

“That said, there are reasons for optimism; our increasing understanding of MDS-associated molecular pathways and a more refined understanding of clinically meaningful trial end points suggest tangible ways to achieve improved clinical outcomes in LR-MDS patients in the near future,” they concluded.


Brunner AM, Leitch HA, van de Loosdrecht AA, Bonadies N. Management of patients with lower-risk myelodysplastic syndromes. Blood Cancer J. 2022;12(12):166. doi:10.1038/s41408-022-00765-8

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