Evolving Approaches: Low-Risk MDS / MDS 07/29/2026

Ep. 1: The Growing Role of Next-Generation Sequencing and IPSS-M in Lower-Risk MDS

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

  • Comprehensive diagnostic evaluation, including bone marrow biopsy and next-generation sequencing (NGS), is essential to distinguish lower-risk myelodysplastic syndromes (MDS) from nonclonal causes of cytopenias.
  • Molecular testing and the Molecular International Prognostic Scoring System (IPSS-M) provide important prognostic information that complements traditional risk stratification with the Revised IPSS (IPSS-R).

As part of a 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 the evolving management of lower-risk MDS, with a particular focus on the role of imetelstat. 

Dr. Carraway highlighted the rapid evolution of MDS management driven by broader adoption of NGS. Molecular testing has improved clinicians’ ability to distinguish clonal hematopoiesis, clonal cytopenia of undetermined significance, and MDS, while identifying patients who may benefit from targeted therapies. Although erythropoiesis-stimulating agents remain the cornerstone of treatment for anemia in lower-risk disease, newer therapies, including luspatercept and imetelstat, have expanded treatment options for patients with transfusion-dependent anemia. In select patients harboring actionable mutations, targeted therapies directed at IDH1 or IDH2 alterations may also play a role.

Dr. Zeidan emphasized the importance of establishing an accurate diagnosis before initiating therapy, noting that dysplastic changes on bone marrow examination alone do not confirm MDS. He stressed that comprehensive evaluation should include assessing vitamin B12, folate, and copper levels and taking a medication history, as well as considering other potential causes of cytopenias alongside cytogenetics, NGS, and bone marrow biopsy. 

Although future diagnostic criteria may incorporate peripheral blood molecular testing, bone marrow evaluation remains the current standard for diagnosing MDS. Dr. Zeidan also noted that younger patients warrant consideration of inherited predisposition syndromes that may influence transplant planning and donor selection.

Dr. Abaza discussed how molecular profiling informs prognosis beyond conventional scoring systems. In her practice, she uses the IPSS-R to distinguish lower-risk from higher-risk disease and then incorporates the IPSS-M to further refine prognosis. Patients whose risk is upstaged by IPSS-M continue to receive therapies appropriate for lower-risk MDS but are referred for transplant evaluation earlier and monitored more closely for treatment response. 

The panel emphasized that molecular risk upstaging alone should not prompt immediate escalation to higher-risk treatment strategies, underscoring the importance of integrating molecular findings with clinical judgment when developing individualized treatment plans.