Dr Badar on Outcomes With Imetelstat in Lower-Risk MDS

Talha Badar, MBBS, MD, hematologist/oncologist, Departments of Hematology and Oncology (Medical), Mayo Clinic, discusses key efficacy findings derived from treatment with imetelstat from the phase 2/3 IMerge trial (NCT02598661) of patients with lower-risk myelodysplastic syndrome (MDS).

Badar begins by stating that it is an exciting time for oncologists treating patients with chronic myeloid disorders, particularly MDS, which can be attributed to 2 recent phase 3 trials thathave demonstrated positive results in this patient population.

For example, the multicenter IMerge trial (NCT02598661) investigating the efficacy of the telomerase inhibitor imetelstat in transfusion-dependent patients with non–deletion 5q, low-risk MDS who were refractory to or relapsed after erythropoiesis-stimulating agents (ESA). Patients enrolled onto the study were randomly assigned 2:1 to receive imetelstat vs placebo. The primary end point of the IMerge trial was 8 weeks of transfusion independence. The secondary end point was 24 weeks of transfusion independence, as well as transfusion independence duration and improvement in hemoglobin.

Results showed superior outcomes with imetelstat vs placebo, with 39.8% of patients achieving transfusion independence at 8 weeks with imetelstat (n = 118) vs 15.0% in the placebo group (n = 60), Badar reports. Notably, the benefit of imetelstat was consistent across various patient subgroups, he adds. Furthermore, the duration of transfusion independence with imetelstat was prolonged at 8 and 24 weeks compared with placebo, Badar states.

Similar to findings from the phase 3 COMMANDS trial (NCT03682536) which evaluated first-line luspatercept-aamt (Reblozyl), specific molecular characteristics were associated with a higher likelihood of responses with imetelstat in the IMerge trial, Badar continues, adding that the agent led to improvements in anemia, as well as longer duration and higher rates of transfusion independence. Additionally, imetelstat demonstrated the ability to decrease the allelic burden of specific mutations implicated in MDS pathogenesis, such as STAT2, SF3B1, and AXL1, suggesting a potential disease-modifying effect, he notes.

These findings highlight the promising therapeutic potential of imetelstat in transfusion-dependent patients with low-risk MDS who have failed prior ESA therapy. The ability of imetelstat to target specific molecular pathways associated with MDS progression underscores its role as a valuable treatment option for this patient population.