Imetelstat Reduces Transfusions, Even Post-Luspatercept

The primary analysis of the phase 3 IMerge trial revealed significant efficacy with imetelstat therapy compared with placebo. Pooled data from the phase 2, 3, and a substudy add to this evidence, showing that despite patients being ESA-ineligible, heavily pretreated, and having a high tumor burden, they still derived clinical benefit.

“Imetelstat is FDA-approved for patients with transfusion-dependent, lower-risk MDS who have previously been exposed to erythropoiesis-stimulating agents. This research shows that imetelstat is also effective at reducing or eliminating transfusion needs in patients who have previously received other drugs used to treat MDS, including luspatercept, lenalidomide, and hypomethylating agents,” Mikkael A. Sekeres, MD, professor of Medicine, chief, Division of Hematology, Leukemia Section,  University of Miami Health System/Sylvester Comprehensive Cancer Center told Blood Cancers Today.

In this analysis, investigators evaluated outcomes for 226 patients who were treated with imetelstat across the IMerge clinical trial program. Most patients (n=188) presented with a high transfusion burden at baseline, as defined by the 2018 revision of the International Working Group criteria, while 38 patients were classified as having a low transfusion burden.

Results showed that 39% of the total patient population achieved red blood cell transfusion independence for at least eight weeks, with a median response duration of 55 weeks. Additionally, 28% reached a duration of at least 24 weeks, and 18% maintained transfusion independence for a year or more. Most patients (n=204) had previously received treatment with erythropoiesis-stimulating agents, while 22 were not eligible for these therapies. Smaller subsets had prior exposure to luspatercept (n=36), lenalidomide (n=26), or hypomethylating agents (n=22). Patient characteristics and efficacy outcomes according to treatment history are detailed in the accompanying data table.

These results not only have key clinical implications, according to the study investigators, but also provide insight into how imetelstat can be integrated into existing regimens for lower-risk MDS.

“I envision a treatment sequence in patients with lower-risk MDS associated with transfusion-dependent anemia starting with an ESA or luspatercept if the MDS is associated with ring sideroblasts or the SF3B1 mutation, then lenalidomide for those with del(5q) MDS, and then imetelstat prior to use of HMAs, said Dr. Sekeres.

As research on treatment sequencing has yet to be reported, clinicians treating patients with lower-risk MDS face challenging decisions when integrating imetelstat.

Dr. Sekeres said, “I think I would still use luspatercept or lenalidomide in appropriate patients prior to use of imetelstat, but would reserve HMAs until after imetelstat, given the low response rate of patients to imetelstat following HMAs. I would want to use imetelstat in patients with relatively preserved platelet and neutrophil counts, given the side effects of the drug, and that generally means earlier in the disease course.

Reference

Komrokji R, et al. 2025 ASCO Annual Meeting; May 30-June 2, 2025; Chicago, IL. Abstract 6569.