Dr Komrokji on the Effect of Prior Treatment on Imetelstat Activity in Transfusion-Dependent LR-MDS

"In this pooled analysis, the activity [of imetelstat] was similar to [that of] the phase 3 [IMerge] trial, with almost 40% of the patients becoming RBC-TI for 8 weeks or more, and we showed that imetelstat retained its activity regardless of prior ESA response. Imetelstat also retained activity regardless of the number of prior therapies [received]."

Rami Komrokji, MD, a vice chair of the Malignant Hematology Department and a senior member of the Malignant Hematology and Experimental Therapeutics Program at the Moffitt Cancer Center; as well as a professor in medicine & oncologic sciences in the College of Medicine at the University of South Florida, discussed the effect of prior treatment on efficacy outcomes with imetelstat (Rytelo) in transfusion-dependent patients with lower-risk myelodysplastic syndromes (LR-MDS) who are relapsed/refractory to, or ineligible for, erythropoiesis-stimulating agents (ESA).

At the 2025 ASCO Annual Meeting, results from a pooled analysis of the phase 2, phase 3, and QTc substudy portions of the IMerge trial (NCT02598661) demonstrated that imetelstat retained clinical activity across various prior treatment exposures.

In this analysis, nearly 40% of patients achieved red blood cell transfusion independence (RBC-TI) for 8 weeks or more, a result consistent with the phase 3 portion of the study, Komrokji shared. Notably, prior ESA exposure did not affect the efficacy of imetelstat, with 8-week RBC-TI rates of 44% and 39% in ESA-naive and ESA-pretreated patients, respectively, he added. Among 22 patients with high endogenous erythropoietin (EPO) levels who were ESA-ineligible, the RBC-TI rate was 36%, Komrokji reported.

Importantly, the analysis highlighted that imetelstat maintained activity following prior treatment with luspatercept (Reblozyl), which has increasingly replaced ESAs as frontline therapy for many patients with LR-MDS, he continued. Of the 36 patients who received prior luspatercept, 31% achieved an 8-week or greater RBC-TI, Komrokji stated, noting that this finding supports a distinct mechanism of action for imetelstat and suggests continued efficacy despite progression on luspatercept. Similarly, clinical benefit was observed in patients previously treated with lenalidomide (Revlimid), although data were limited, he added.

In contrast, patients with prior hypomethylating agent (HMA) exposure demonstrated lower response rates, Komrokji detailed. Among 22 such patients, only 14% achieved RBC-TI for 8 weeks or more, reflecting a known trend of diminished responses following HMA failure, he said. Despite this, imetelstat retained activity across lines of therapy, including in patients treated beyond second-line settings, Komrokji reiterated.

Overall, these findings support imetelstat’s role as a potential therapeutic option for patients with LR-MDS, particularly after luspatercept or ESA progression, and reinforce the importance of its distinct biological mechanism, Komrokji concluded.