Updated NCCN Guidelines Recommend Imetelstat to Treat Anemia in Lower-Risk MDS

Updated NCCN Guidelines Recommend Imetelstat to Treat Anemia in Lower-Risk MDS

The National Comprehensive Cancer Network (NCCN) has updated its clinical practice guidelines in oncology to now recommend imetelstat (Rytelo) as a Category 1 and 2A treatment for symptomatic anemia in patients with lower-risk myelodysplastic syndromes (MDS).¹

Treatments are designated as Category 1 and 2A when there is a strong NCCN consensus, with at least 85% agreement, that the intervention is appropriate.

The FDA approved imetelstat in June 2024 for the treatment of adult patients with low- to intermediate-1 risk MDS with transfusion-dependent anemia who require at least 4 red blood cell units over 8 weeks and for those who have not responded to, have lost response to, or are ineligible for erythropoietic stimulating agents (ESAs).² This approval was based on data from the phase 3 IMerge trial (NCT02598661) which was published in The Lancet in December 2023 and supports the NCCN’s updated guidelines.

“We believe that the placement of [imetelstat] in the updated MDS NCCN Guidelines reflects the strength of our phase 3 data and the US Prescribing Information, and that these updates will help to increase awareness and uptake of [imetelstat] as a compelling new treatment option for these patients,” Faye Feller, MD, Geron’s executive vice president and chief medical officer, said in a press release.¹ “We are encouraged by the increasing dialogue across hematologists rethinking treatment approaches and sequencing given the availability of [imetelstat] for eligible lower-risk MDS patients with transfusion-dependent anemia.”

Imetelstat is an liquidated oligonucleotide telomerase inhibitor approved for treating adult patients with low-to-intermediate-1 risk MDS with transfusion-dependent anemia.1 The first-in-class treatment inhibits telomerase enzymatic activity and is the first and only telomerase inhibitor approved by the FDA.

The IMerge trial was a randomized, multicenter, phase 2/3 trial which enrolled patients aged 18 years and older with MDS and an ECOG performance status of 0, 1, or 2. Patients were randomly assigned to 1 of 2 arms: Two-thirds of the patients received imetelstat while the other third received a placebo.³

The primary end point for parts 1 and 2 of the trial were evaluating the percentage of patients without any red blood cell transfusion during any consecutive 8-week period. Secondary end points included assessing adverse events, duration of red blood cell transfusion independence (TI), time to 8-week red blood cell TI, percentage of patients with hematologic improvement, percentage of patients with complete or partial remission, overall survival, progression-free survival, time to progression to acute myeloid leukemia, amount of red blood cell transfusions, relative change in red blood cell transfusions, percentage of patients receiving any myeloid growth factors, and pharmacokinetics.

IMerge met its primary and key secondary end points as patients enrolled and treated with imetelstat had significantly higher rates of red blood cell transfusion independence (39.8%; 95% CI, 30.9%-49.3%) vs those treated with placebo for at least 8 consecutive weeks (15.0%; 95% CI, 7.1%-26.6%; P <.001).³ Rates of red blood cell transfusion independence for at least 24 weeks were 28.0% with imetelstat (95% CI, 20.1%-37.0%) and 3.3% with placebo (95% CI, 0.4%-11.5%; P <.001).

Red blood cell transfusion independence was also durable and sustained in the imetelstat-treated population, with a median duration of approximately 1 year for 8-week responders and 1.5 years for 24-week responders, respectively.

Safety findings showed that the most frequently seen adverse events were laboratory abnormalities, including thrombocytopenia, decreased white blood cells, neutropenia, increased aspartate aminotransferase, increased alkaline phosphatase, increased alanine aminotransferase, fatigue, prolonged partial thromboplastin time, arthralgia/myalgia, COVID-19 infections, and headache.

References

1. Geron announces updated NCCN guidelines® recommending RYTELO™ (imetelstat) for the treatment of symptomatic anemia in patients with lower-risk MDS. News release. Geron Corporation. July 26, 2024. Accessed July 29, 2024. https://tinyurl.com/4sz4t6c8
2. Geron announces FDA approval of RYTELO™ (imetelstat), a first-in-class telomerase inhibitor, for the treatment of adult patients with lower-risk MDS with transfusion-dependent anemia. Geron Corporation. News release. June 6, 2024. Accessed July 29, 2024. https://tinyurl.com/ym5v86d
3. Platzbecker U, Santini V, Fenaux P, et al. Imetelstat in patients with lower-risk myelodysplastic syndromes who have relapsed or are refractory to erythropoiesis-stimulating agents (IMerge): a multinational, randomized, double-blind, placebo-controlled, phase 3 trial. Lancet. 2024;403(10423)P249-260. doi:10.1016/S0140-6736(23)01724-5