Clinical Decision-Making in Lower-Risk MDS: Timing and Patient Selection for Targeted Therapies

When deciding whether to initiate treatment for anemia in low-risk myelodysplastic syndrome (MDS), the clinical context and patient symptoms often outweigh any strict hemoglobin threshold. Rather than focusing solely on lab values, it is essential to assess how the patient is functioning—whether they are experiencing fatigue, shortness of breath, or reduced exercise tolerance. In symptomatic patients, even with hemoglobin levels just under 10 g/dL, treatment may be warranted. For patients with hemoglobin below 9 g/dL, therapy is typically considered regardless of symptoms.

Transfusions play a key role in managing acute or severe anemia, offering rapid relief and a preview of how a patient might respond to red cell support. However, transfusion dependency is not a requirement to initiate therapies like ESAs or luspatercept in real-world practice. Starting treatment earlier, even before patients become transfusion dependent, may help improve hemoglobin levels, alleviate symptoms, and potentially delay disease progression.

For patients with milder anemia and no urgent need for hemoglobin correction, ESAs or luspatercept can be introduced without preceding transfusions. While ESAs generally require time to take effect, transfusions can still be used in the interim for more immediate symptom control. Overall, the decision to treat should be individualized, with an emphasis on symptom burden, functional status, and quality of life rather than rigid laboratory cutoffs.