Dr Ball on Data From from the IMerge Trial in Low– to Intermediate-Risk MDS

Somedeb Ball, MBBS, assistant professor of medicine, Division of Hematology Oncology, Department of Medicine, Vanderbilt University Medical Center, discussed the efficacy of the telomerase inhibitor imetelstat as evaluated in the phase 2/3 IMerge/MDS3001 trial (NCT02598661 in the treatment of low– to intermediate-risk myelodysplastic syndromes (MDS), highlighting key takeaways from this study.

This double-blind, randomized trial evaluated the treatment with imetelstat vs placebo. Imetelstat has been explored in various oncological contexts, but the agents role in MDS has become particularly significant, Ball explains. Notably, on March 24, 2024, in a 12 to 2 vote, 

the FDA’s Oncologic Drugs Advisory Committee agreed that the benefits of imetelstat outweigh the risks

 in the treatment of transfusion-dependent anemia in adult patients with International Prognostic Scoring System (IPSS) low- to intermediate-1–risk MDS who have not responded to, no longer respond to, or are ineligible for treatment with erythropoiesis-stimulating agents (ESAs).

The IMerge trial evaluated participants who fit this criteria, as well as who had a baseline serum erythropoietin level exceeding 500 U/L, indicating probable resistance to erythropoietin-based therapies. Ball highlights the challenge in managing patients with MDS who do not respond to conventional ESAs, underscoring the utility of imetelstat.

Furthermore, the trial's outcomes revealed a notable efficacy of imetelstat in achieving transfusion independence compared to the placebo group, he continues. This was quantified by a significant increase in the hemoglobin levels, Ball explains.

These findings position imetelstat as a promising therapeutic option for this patient population, he continues. Additionally, Ball shares his hoped for an FDA approval of the agent in patients with low– to intermediate-risk MDS who are relapsed/refractory to other treatment options. However, luspatercept-aamt (Reblozyl) is approved by the FDA for the treatment of anemia without prior ESA use in these patients patients who may require regular red blood cell transfusions, Ball concludes.

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Somedeb Ball, MBBS, discusses data from the phase 3 IMerge trial of imetelstat vs placebo in low– to intermediate-risk myelodysplastic syndromes. 



Dr Ball on the Use of Luspatercept in MDS With Anemia

Somedeb Ball, MBBS, assistant professor, medicine, Division of Hematology Oncology, Department of Medicine, Vanderbilt University Medical Center, discusses the benefits of luspatercept-aamt (Reblozyl) for patients with anemia due to their myelodysplastic syndrome (MDS).

Luspatercept is a fusion protein that contains a modified activin receptor that acts on the TGF-β ligand and improves upon outcomes with late erythropoietin-stimulating agents (ESAs) to alleviate anemia in patients with MDS, Ball says. Early research has shown that luspatercept is active in patients with MDS with anemia that is refractory to prior ESAs, Ball notes. In 2020, 

 for adult patients with lower-risk MDS with anemia with ring sideroblasts who have progressed on an ESA and require at least 2 red blood cell (RBC) units across 8 weeks. Data from the pivotal phase 3 MEDALIST trial (NCT02631070), which supported the approval, also showed that this agent was effective in patients with 

Luspatercept was further evaluated in ESA-naive patients with anemia due to lower-risk MDS requiring RBC transfusions in the randomized, phase 3 COMMANDS trial (NCT03682536), findings from which were presented at the 

. In the phase 3 trial, luspatercept was compared with epoetin alfa, the previous frontline standard of care for patients with lower-risk MDS with transfusion-dependent anemia, according to Ball. The primary end point of COMMANDS was RBC transfusion independence for at least 12 weeks with a mean hemoglobin increase of at least 1.5 g/dL within the first 24 weeks.

In COMMANDS, 58.5% of patients in the luspatercept arm achieved the primary end point compared with 31.2% of those in the epoetin alfa arm. The benefit with luspatercept was consistent across patient subgroups when patients were stratified by baseline serum erythropoietin levels, baseline RBC transfusion burden, 

 mutation status, and ring sideroblast status, Ball emphasizes. Data from COMMANDS supported the 

 for the treatment of anemia in ESA-naive patients with very low– to intermediate-risk MDS who may require regular RBC transfusions.

Somedeb Ball, MBBS, discusses the benefits of luspatercept for patients with anemia due to a myelodysplastic syndrome.

Somedeb Ball, MBBS

Articles

Dr Ball on Data From from the IMerge Trial in Low– to Intermediate-Risk MDS

Dr Ball on the Use of Luspatercept in MDS With Anemia