Impact of Mutational Status on Response in IMerge Phase 3 Study in MDS

EP: 1.Current Treatment Landscape for Patients with Lower-Risk MDS

EP: 2.MDS: Transfusion Independence Across Different Risk Subgroups in IMerge Phase 3 Trial

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EP: 3.Impact of Mutational Status on Response in IMerge Phase 3 Study in MDS

EP: 4.Durable Transfusion Independence in Lower-Risk MDS

EP: 5.MDS: Patient-Reported Outcomes and Imetelstat Toxicity in IMerge Phase 3 Trial

EP: 6.Biomarker Analysis and Patient-Reported Outcomes from COMMANDS Study in MDS

EP: 7.MDS: Canakinumab Phase 1b/2 Study

EP: 8.Clinical Implications of Recent Data in MDS

This is a video synopsis of a discussion featuring Gary J. Schiller, MD, chief of the Hematological Malignancy/Stem Cell Transplantation program at the David Geffen School of Medicine at UCLA Health Jonsson Comprehensive Cancer Center.

Gary J. Schiller, MD, discusses a presentation by Dr Santini that discussed the impact of mutational status on response in the imetelstat IMerge trial. This follows another abstract by the same group showing patients with erythropoiesis-stimulating agent (ESA) refractory MDS have different responses based on their IPSS-R molecular risk category, with higher risk patients having lower response likelihood.

In the IMerge trial, imetelstat, a first-in-class telomerase inhibitor, was compared to placebo in lower-risk MDS without 5q deletion. Patients had relapsed/refractory disease or were otherwise ineligible for ESAs. Mutational data was available for 165 of 178 patients, assigned to either imetelstat or placebo.

As expected, patients with a “low risk” mutational profile including SF3B1, U2AF1, SRSF2, ZRSR2, TET2, DNMT3A, RUNX1, ASXL1 and EZH2 mutations had better transfusion independence responses to imetelstat vs placebo. Transfusion independence >24 weeks was 0% in the placebo but 9.1% in the imetelstat arm for these patients.

In summary, mutational profile predicts response to imetelstat similar to ESA agents. In this randomized trial, imetelstat treated patients had significantly better responses than placebo regardless of mutations. However, adverse mutation profiles still predict lower response likelihood independent of treatment arm.

*Video synopsis is AI-generated and reviewed by Targeted Oncology editorial staff.