New Approaches in the Treatment of Patients With Low-Risk MDS

At the virtual 2020 Lymphoma, Leukemia & Myeloma Congress, Sangmin Lee, MD, Weill Cornell Medicine, New York, provided an overview of novel strategies for patients with low-risk myelodysplastic syndromes (MDS).

MDS is a heterogeneous disease. Tools frequently used for risk stratification in this setting include using IPSS and IPSS-R, which incorporate cytogenetics, bone marrow blasts, and degree cytopenias.

“By IPSS-R, patients can be stratified to very low-, low-, intermediate-, high-, very high-risk categories, and both overall survival (OS) and rate of AML transformation vary depending on the IPSS-R classification,” Dr Lee explained.

Generally, patients with lower-risk MDS by IPSS-R have longer OS and are less likely to have AML transformations. When referring to patients with MDS as having lower-risk disease, this often includes patients with very low- and low-risk, and some patients with intermediate-risk by IPSS-R. The majority of these patients have decreased blasts in their bone marrow.

For patients with lower-risk MDS, the general goal is to improve transfusion dependence, whereas for higher-risk MDS patients goals are to also improve OS, prevent progression to AML, and improve cytopenias.

For patients with MDS who are not transfusion-dependent or who need very infrequent transfusions, supportive care with transfusion support is reasonable. With regards to intervention, several options are currently available, including growth factor support, thrombopoietin receptor agonist, lenalidomide, luspatercept, hypomethylating agents, and novel agents emerging in the context of clinical trials.

Ultimately, a key goal for patients with lower-risk MDS is improvement of cytopenias. Anemia is the most common issue in this patient population, and there are several therapeutic options available in this setting.

Approximately 40% of patients with low-risk MDS require red blood cell transfusions, which can lead to iron overload. Iron overload has been tied to end-organ damage, including hepatic, cardiac, and endocrine dysfunctions. Iron chelation can be considered for patients with ferritin >1,000, although tolerability of iron chelation agents are a concern, because not all patients can tolerate these agents.

Approximately 80% of patients with MDS have anemia, which is significantly associated with morbidity. There are a number of erythropoiesis-stimulating agents available for patients MDS, the most common being darbepoetin or epoetin alfa.

Erythropoietin stimulating agents are still the standard first-line therapy for anemia in patients with lower-risk MDS. TPO receptor agonists can be considered in certain patients, and after erythro-stimulating agents, lenalidomide can be considered, especially in those with deletion 5q abnormality.

In patients with MDS with ring sideroblasts or SF3B1 mutations, luspatercept should be considered. In addition, hypomethylating agents can be considered and in certain instances, oral decitabine is an option.

“If none of these approaches work, there are a number of novel agents that are in development for lower-risk MDS patients. Patients without standard-of-care options should be referred for clinical trials,” Dr Lee concluded.—Hina Porcelli