Evolving Approaches: Low-Risk MDS / MDS 08/07/2026

Ep. 4: Personalizing Therapy Decisions in Lower-Risk Myelodysplastic Syndromes

Professional woman with blonde hair wearing a black pinstripe blazer, smiling confidently with arms crossed in a modern office setting. Hetty Carraway, MD Smiling man with beard wearing a white shirt, professional headshot, suitable for oncology or cancer research content, emphasizing healthcare and medical expertise. Rahul Gosain, MD, MBA Close-up portrait of a woman wearing a purple and pink patterned hijab, looking confidently at the camera with a neutral background. Yasmin Abaza, MD Professional portrait of a smiling man in a suit and blue shirt against a gray background, suitable for medical or healthcare-related content. Thomas LeBlanc, MD, MA Portrait of a male doctor in a white lab coat at Yale Cancer Center, smiling confidently, with a neutral background. Amer Zeidan, MBBS, MD

Key Points

  • Treatment sequencing in lower-risk myelodysplastic syndromes (MDS) should consider long-term disease trajectory, symptom burden, erythropoietin (EPO) levels, transfusion dependence, and patient goals.
  • Many patients will require multiple therapies over time, making strategic sequencing of luspatercept, erythropoiesis-stimulating agents (ESAs), imetelstat, and other options essential.
  • Shared decision-making and early planning for future treatment transitions, including transplant evaluation when appropriate, are critical components of lower-risk MDS management.

In this Clinical Insights discussion, Rahul Gosain, MD, MBA, Wilmot Cancer Institute, and Hetty Carraway, MD, of Cleveland Clinic, were joined by Yasmin Abaza, MD, of Northwestern Medicine; Thomas LeBlanc, MD, MA, of Duke Cancer Center; and Amer Zeidan, MBBS, MD, of Yale School of Medicine, to discuss evolving treatment strategies for patients with lower-risk MDS.

The panel emphasized that lower-risk MDS is a chronic disease, and patients may live for years while experiencing progressive anemia, fatigue, and transfusion dependence. Because many patients may require multiple therapies throughout their disease course, the panel noted that clinicians must carefully consider how to sequence available options to maximize the duration of benefit while maintaining quality of life. Dr. LeBlanc remarked that he generally starts with luspatercept, followed by reassessment of serum EPO levels and consideration of ESAs in select patients. For those who remain transfusion-dependent, imetelstat represents an important next-line option before considering more intensive treatments such as hypomethylating agents.

Imetelstat may be particularly valuable for patients with higher EPO levels or those unlikely to benefit from ESA-based approaches, Dr. Carraway said. She noted that real-world practice often differs from the IMerge trial population, in which participants had not previously received treatment with luspatercept or lenalidomide, and emerging experience suggests imetelstat may maintain activity after prior therapies. 

The panel discussed the importance of using available therapies at the appropriate time, recognizing that patients may benefit from sequential approaches rather than moving prematurely to more intensive treatments that may negatively affect quality of life.

The discussion also reinforced the importance of continued patient-centered care. Dr. Carraway emphasized that treatment decisions should begin with understanding patient goals, including addressing symptoms such as fatigue and shortness of breath and maintaining independence. Although anemia remains a primary concern for many patients with lower-risk MDS, clinicians should also consider molecular risk factors, transplant eligibility, and future treatment planning. Early conversations about potential next steps, including transplant consultation when appropriate, can help patients understand their options and prepare for changes in disease status or treatment response.