Lower-risk myelodysplastic syndromes (MDS) have long posed a clinical balancing act: managing symptomatic anaemia, while delaying progression and preserving quality of life. Recent years have brought meaningful advances, with the emergence of targeted agents expanding options beyond erythropoiesis-stimulating agents alone.
As part of our Haematology Horizons practice pearl series, Dr Douglas Tremblay (Icahn School of Medicine at Mount Sinai, New York City, NY, USA) shares his expert insights on how luspatercept and imetelstat are reshaping first- and second-line treatment strategies for lower-risk MDS. He shares practical insights on patient selection, sequencing therapy, managing cytopenias and where the greatest unmet needs remain in contemporary practice.
Q. How has the treatment landscape changed for lower-risk MDS? Thankfully the treatment landscape for lower-risk MDS has evolved over the last decade to offer more treatment options for patients who require red blood cell (RBC) transfusions. Specifically, the introduction of luspatercept for certain subtypes of MDS who have ring sideroblasts and/or an SF3B1 mutation, as well as frontline instead of erythropoiesis-stimulating agents (ESAs), have been a welcomed addition. The approval of imetelstat for RBC transfusion-dependent lower-risk MDS that is ESA refractory or ineligible has also provided another effective agent. Q. What most influences your treatment strategy in lower-risk disease? Lower risk MDS is heterogenous disease and some patients who are asymptomatic and without significant cytopenias may be able to be monitored. However, in those that are RBC transfusion-dependent or anaemic and fatigued, there is rationale to treat patients to improve their hemoglobin. Disease factor including mutational status (i.e. SF3B1), the presence of ring sideroblasts on bone marrow, erythropoietin (EPO) level and patient preference all factor into the treatment decisions. Q. How has luspatercept changed the current front line treatment paradigm for lower-risk MDS? Luspatercept for frontline MDS has introduced an extremely well tolerated agent that is effective, particularly in ESA-naïve patients who harbour an SF3B1 mutation or ring sideroblasts. It’s use in patients who are not transfusion dependent continues to be evaluated and may offer a means to prevent developing RBC transfusion dependence, which is associated with a decreased quality of life. Q. How has imetelstat changed the current second line treatment paradigm for lower-risk MDS? Imetelstat offers an effective treatment for transfusion dependent lower risk MDS and is equally effective independent of SF3B1 mutational status. In patients who are not responding to ESA and/or luspatercept, this is a great option before moving towards hypomethylating agents (HMA)-based therapies. In addition, there is evidence of imetelstat reducing mutational burden, which may be effective in controlling disease progression. Q. Which patients are the best candidates for luspatercept and imetelstat in your experience? Luspatercept is great option as a frontline agent or in patients who are ESA-ineligible or have failed an ESA, but it is most effective in subsets of patients with SF3B1 mutation and ring sideroblasts. However, I will also consider it in patients who lack these characteristics. Imetelstat is a reasonable option for patients who have failed an ESA and luspatercept before moving to HMA, in my opinion. It should be given with caution in patients with concurrent neutropenia as this may worsen, although reassuringly recent data suggest that those patients who have treatment related cytopenias actually have improved survival. Q. How early in the treatment course do you consider luspatercept and imetelstat? For the appropriate ESA-naïve patient who is able to come in every three weeks, I consider luspatercept. Imetelstat is generally reserved for later lines of therapy Q. How do you approach patient selection given the potential for cytopenias or other toxicities? This is not a concern for luspatercept, but imetelstat does lead to exacerbation of cytopenias. However, recent data suggest that in fact the occurrence of these cytopenias is associated with improved survival, so I would not use this as a reason to discontinue imetelstat. Q. What remains the biggest unmet need in lower-risk MDS despite recent advances? In patients who have failed all available options (ESA, luspatercept, imetelstat), newer therapies that may be used before moving on to low-dose HMA are urgently needed. In addition, therapies that significantly modify the disease course and improve symptoms independent of hematologic recovery also represents an unmet need. Already registered? Login below.
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This content has been developed independently by Touch Medical Media for touchHAEMATOLOGY. Views expressed are the speaker’s own and do not necessarily reflect the views of Touch Medical Media.
Cite: Contemporary treatment of lower-risk myelodysplastic syndromes. touchHAEMATOLOGY. 11th February 2026.
Editor: Sophie Nickelson, Editorial Director
Disclosures: Douglas Tremblay is a consultant for Sobi, Refined Oncology, AbbVie, Pharmaessentia, Geron, GSK and Cogent Biosciences. He has received grant/research support from Sobi, Sumitomo, Geron, and Cogent Biosciences.
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