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Patients with lower-risk myelodysplastic syndromes (MDS) who relapsed or were refractory to standard treatment achieved improved rates of red blood cell (RBC) transfusion independence with an investigational, first-in-class telomerase inhibitor, the randomized IMerge trial showed.

Among heavily transfused patients who failed on erythropoiesis-stimulating agents (ESAs), those treated with imetelstat had significantly higher rates of RBC transfusion independence for at least 8 weeks compared with those treated with placebo (40% vs 15%, P=0.0008), reported Uwe Platzbecker, MD, of the University Hospital Leipzig in Germany, and colleagues.

Moreover, RBC transfusion independence was sustained with imetelstat, with 83% of 8-week responders having a single continuous transfusion independence period compared with 56% of responders in the placebo group, they noted in .

"The prolonged transfusion independence seen with imetelstat in this patient population underscores the potential for this novel agent as a second-line therapy in lower-risk MDS," Platzbecker's group wrote.

While ESAs are currently the standard first-line treatment for symptomatic anemia in patients with lower-risk MDS, many patients do not respond or lose response within roughly 2 years. A of imetelstat demonstrated a meaningful durable transfusion independence rate across a broad range of heavily transfused patients.

In August, drugmaker Geron announced that the FDA had based on the IMerge data for imetelstat as a treatment for transfusion-dependent anemia in low- to intermediate-1 risk MDS patients who relapsed on, were refractory to, or are ineligible for ESAs. A decision is expected by June 2024.

In a , Mrinal Patnaik, MBBS, of the Mayo Clinic in Rochester, Minnesota, wrote that given the few options for patients with RBC transfusion-dependent MDS, "the advent of imetelstat is truly an important milestone."

However, Patnaik pointed out that the drug is associated with "substantial" thrombocytopenia and neutropenia. For routine use of imetelstat, practitioners will "need to optimize supportive care measures unlike what they are normally used to for therapies for anemia-directed, lower-risk myelodysplastic syndromes, such as ESA and luspatercept [Reblozyl]."

With the recent FDA approval of luspatercept for the front-line management of anemia in patients with lower-risk MDS (regardless of ring-sideroblast status), "data would be needed in an expedited manner to see if patients treated with luspatercept respond to imetelstat or not," he wrote. "Given all that our patients already endure, the appropriate and safe use of this drug is paramount in ensuring that we do not make the treatment of disease more grievous than the endurance of the same."

The double-blind was conducted at 118 sites in 17 countries and included 178 patients. From September 2019 to October 2021, 118 patients were randomly assigned to imetelstat 7.5 mg/kg every 4 weeks and 60 patients were assigned to placebo.

Patients had a median age of 72, and 62% were men. They were heavily transfused with a median previous RBC transfusion burden of 6.0 units over 8 weeks.

Overall, 90% of patients had previously received an ESA, and 6% had previously received luspatercept.

After a median follow-up of 19.5 months for the imetelstat group and 17.5 months for the placebo group, patients received a median of eight treatment cycles of each, with a median duration of treatment of 33.9 weeks and 28.3 weeks, respectively.

The primary endpoint of RBC transfusion independence for at least 8 weeks was also reached in 45% and 32% of patients with and without ring sideroblasts in the imetelstat group versus 19% and 9%, respectively, in the placebo group.

Among patients who had 8-week RBC transfusion independence, the median increase in blood hemoglobin from before treatment to the peak during the longest independence period was 3.55 g/dL in the imetelstat group versus 0.80 g/dL in the placebo group.

"These results also correspond to improved patient-reported fatigue in patients receiving imetelstat," Platzbecker and team wrote, with patients in the imetelstat group more likely to have sustained meaningful improvements in fatigue, and with shorter median time to improvement, compared with those in the placebo group.

Grade 3 or 4 treatment-emergent adverse events (TEAEs) occurred in 91% of patients receiving imetelstat and 47% of those receiving placebo. The most common grade 3/4 TEAEs in patients taking imetelstat were neutropenia (68% vs 3% with placebo) and thrombocytopenia (62% vs 8%). No treatment-related deaths were reported.

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