Evolving Approaches: Low-Risk MDS / MDS 08/04/2026

Ep. 3: Managing Imetelstat Toxicities 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

  • Cytopenias, particularly thrombocytopenia and neutropenia, are the most common adverse events associated with imetelstat but are typically transient and manageable with supportive care.
  • Early declines in blood counts may represent an on-target effect of imetelstat and have been associated with improved erythroid responses rather than treatment failure.
  • Clinicians should counsel patients about expected count changes, monitor closely during initial cycles, and allow adequate treatment duration before assessing response.

In this Clinical Insights episode, 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 practical management of imetelstat in patients with lower-risk myelodysplastic syndromes (MDS). Following a review of treatment sequencing and patient selection, the panel focused on common adverse events associated with imetelstat, strategies for monitoring and supportive care, and clinical pearls for helping clinicians and patients navigate therapy.

Dr. Abaza emphasized that cytopenias are the most frequently observed adverse events with imetelstat, with grade 3 or 4 thrombocytopenia and neutropenia occurring in a substantial proportion of patients treated in clinical trials. However, she noted that these laboratory abnormalities do not necessarily translate into significant clinical complications. Rates of severe bleeding events and febrile neutropenia were low, suggesting that early declines in blood counts often represent changes in laboratory values rather than an immediate safety concern. She highlighted the importance of patient education, explaining that count reductions may indicate the drug is working through its intended mechanism of targeting malignant clones.

The panel discussed practical approaches to monitoring and managing these cytopenias. They recommended frequent blood count monitoring during the first 2 treatment cycles, with additional liver function test monitoring during the initial cycle. Dr. Abaza noted that treatment delays may be required until platelet and absolute neutrophil counts recover, but most patients experience improvement within approximately 2 weeks. Supportive measures, including platelet transfusions, growth factor support, and antimicrobial prophylaxis, may be considered based on individual patient risk factors. Dose modifications may be necessary for recurrent or severe cytopenias, but the panel emphasized that these events generally become less problematic after the initial treatment cycles.

Dr. Zeidan, who contributed to analyses evaluating the relationship between cytopenias and treatment response, explained that platelet and neutrophil count reductions correlate with subsequent erythroid responses. Similar to observations with lenalidomide, analyses of count changes as continuous variables demonstrated an association between specific reductions and clinical benefit. 

The panel also emphasized the importance of allowing adequate time for imetelstat to demonstrate activity, noting that some patients may require 4 to 6 treatment cycles before achieving meaningful improvements in hemoglobin.