NCCN Recommends Rytelo for Anemia in Patients With MDS

Rytelo is recommended for patients with lower-risk myelodysplastic syndromes (MDS) who experience anemia.

The National Comprehensive Cancer Network (NCCN) now recommends Rytelo (imetelstat) as a treatment for patients with lower-risk myelodysplastic syndrome (MDS) who have symptomatic anemia.

The NCCN is comprised of leading oncology centers. They publish treatment guidelines to guide cancer care that are based on the latest clinical evidence. The organization now states that Rytelo is a Category 1 and Category 2A therapy for this patient population.

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 Rytelo in June 2024 for the treatment of adult patients with low- to intermediate-1 risk MDS with transfusion-dependent anemia who require at least four red blood cell units over eight weeks and for those who have not responded to, have lost response to, or are ineligible for erythropoietic stimulating agents (ESAs; medications used to stimulate the bone marrow to produce more red blood cells).

The approval was based on data from the phase 3 IMerge trial which was published in The Lancet in December 2023 and supports the NCCN’s updated guidelines.

“We believe that the placement of Rytelo 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 Rytelo as a compelling new treatment option for these patients,” Dr. Faye Feller, Geron’s executive vice president and chief medical officer, said in a press release.“We are encouraged by the increasing dialogue across hematologists rethinking treatment approaches and sequencing given the availability of Rytelo for eligible lower-risk MDS patients with transfusion-dependent anemia.”

Rytelo works by inhibiting telomerase enzymatic activity (which is associated with cell production) and is the first and only telomerase inhibitor approved by the FDA.

The IMerge trial was a randomized, multicenter, phase 2/3 trial that enrolled patients aged 18 years and older with MDS and an ECOG performance status of 0, 1 or 2, indicating that they can perform — at the very least — all of their self-care activities. Patients were randomly assigned to 1 of 2 arms: Two-thirds of the patients received Rytelo while the other third received a placebo (inactive drug).

The primary end point for parts 1 and 2 of the trial evaluated the percentage of patients without any red blood cell transfusion during any consecutive eight-week period. Secondary end points included assessing side effects, duration of red blood cell transfusion independence, time to eight-week red blood cell transfusion independence, 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 how the body interacts with the drug.

IMerge met its primary and key secondary end points as patients enrolled and treated with Rytelo had significantly higher rates of red blood cell transfusion independence (39.8%) versus those treated with placebo for at least eight consecutive weeks (15%). Rates of red blood cell transfusion independence for at least 24 weeks were 28% with Rytelo and 3.3% with placebo.

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

Safety findings showed that the most frequently seen side effects from Rytelo were laboratory abnormalities, including thrombocytopenia (decreased type of white blood cell called thrombocytes), decreased white blood cells, neutropenia, increased aspartate aminotransferase, increased alkaline phosphatase, increased alanine aminotransferase (increase in a protein that could indicate liver damage), fatigue, longer time to blood clot, pain, COVID-19 infections and headache.

“With [Rytelo], we have an option that comes between ESAs and [Reblozyl (luspatercept)], and something that I would consider to be more traditional chemotherapy like a hypomethylating agent,” said Dr. Mikkael A. Sekeres, in an interview with CURE®’s sister publication, Targeted Oncology.

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