Dr Komrokji on the Clinical Integration of Imetelstat for Lower-Risk MDSLR-MDS

"[My advice is to] spend some time making sure you have he right diagnosis and risk stratify the patients to make sure they are lower risk. In most of the cases, we are treating anemia and half of these patients, over time, become transfusion dependent. Nowadays, [treatment] is tailored based on the subtype of the MDS."

Rami Komrokji, MD, vice chair of the Malignant Hematology Department at Moffitt Cancer Center and professor of medicine and oncologic sciences at the University of South Florida, offered guidance on incorporating imetelstat (Rytelo) into clinical practice for patients with lower-risk myelodysplastic syndromes (LR-MDS) who are transfusion dependent and relapsed/refractory to, or ineligible for, erythropoiesis-stimulating agents (ESAs).

Findings from a pooled analysis of the phase 2, phase 3, and QTc substudy components of the IMerge trial (NCT02598661) presented at the 2025 ASCO Annual Meeting demonstrated that imetelstat elicited clinical benefit across multiple prior therapy exposures, including in patients previously treated with luspatercept (Reblozyl).

LR-MDS represents approximately 60% of all MDS cases, and anemia is the primary clinical challenge in 90% of these patients, Komrokji began. Accurate diagnosis and risk stratification remain critical steps before initiating therapy. First-line treatment selection is generally subtype specific: lenalidomide (Revlimid) is used for patients with del(5q), while luspatercept is preferred for those with SF3B1 mutations. ESAs may still be considered first-line in patients without del(5q) or SF3B1 mutations, with luspatercept positioned as second-line in those ineligible for or refractory to ESAs, he added.

For patients who remain transfusion dependent after ESA and luspatercept therapy, imetelstat offers a viable second-line treatment option. Appropriate candidates for imetelstat typically have preserved hematologic function, including platelet counts greater than 75 × 10⁹/L and absolute neutrophil counts greater than 1.0 × 10⁹/L, Komrokji noted. He added that hypomethylating agents are generally deferred to later lines of therapy, particularly for patients with concurrent cytopenias such as thrombocytopenia or neutropenia.

Overall, the treatment paradigm for LR-MDS continues to evolve, with imetelstat providing a new option for patients with transfusion-dependent anemia following failure of first-line agents, Komrokji concluded.