For Patients With Myelodysplastic Syndrome, New Treatment Option Rytelo Could Reduce Need for Blood Transfusions & Improve Quality of Life

An Exciting New Option For MDS Patients

• Imetelstat (brand name Rytelo), a new drug known as a telomerase inhibitor, has been approved by the Food and Drug Administration (FDA) for low-risk myelodysplastic syndrome (MDS).
• The promising new drug may decrease the frequency that a patient needs blood transfusions, which can significantly improve quality of life.
• The drug works by preventing the enzyme telomerase from lengthening the ends of DNA (called telomeres). Telomerase in often found in cells that undergo frequent replication — such as stem cells and cancer cells.
• Treatment for MDS typically consists of slowing the disease course and managing symptoms. Often, patients have to undergo frequent blood transfusions.
• With Rytelo, patients may need fewer transfusions — but they should discuss potential side effects with their doctors.

There’s some wonderful news for people living with myelodysplastic syndrome (MDS), a rare type of blood cancer: the U.S. Food and Drug Administration (FDA) has recently approved a new treatment option that could reduce the need for regular blood transfusions. Over 70% of patients with MDS, are classified as having lower-risk disease, and the majority of these patients will require blood transfusions as a component of their care to treat a common complication: anemia, or a lack of healthy red blood cells. This novel therapy known as Imetelstat (brand name Rytelo ) is indicated for the treatment of adult patients with low- to intermediate-risk MDS with transfusion-dependent anemia requiring four or more red blood cell units over eight weeks who have not responded to, have lost response to, or are ineligible for erythropoiesis-stimulating agents (ESA). ESAs are medications which stimulate the bone marrow to make red blood cells. “With the approval and availability of Rytelo, we believe eligible patients with LR [low risk] MDS can potentially experience meaningful clinical benefit, particularly the potential for greater than 24 weeks of freedom from the burden of red blood cell transfusions and symptomatic anemia," said Dr John A. Scarlett , chairman and chief executive officer of Geron , in a news release. “The approval of Rytelo as the first telomerase inhibitor is a testament to the power of our science and the passion of our people to innovate in the field of blood cancer .”

How Does Rytelo Work?

Rytelo is a drug that targets telomerase, an enzyme that helps certain cells, including some cancer cells, divide and grow by protecting the ends of their DNA called telomeres. This drug aims to stop the growth of cancer cells by inhibiting telomerase.

What are Telomeres?

Telomeres are the ends of our DNA. Each time a cell divides, its telomeres get a bit shorter. When telomeres get too short, the cell can’t divide anymore. Telomerase is an enzyme that can make telomeres longer. It’s usually not in most normal cells — but is in stem cells and cancer cells. Cancer cells use telomerase to keep growing and dividing.

Why Block Telomerase?

Blocking telomerase can stop cancer cells from growing. Rytelo (imetelstat) does this by binding to telomerase and stopping it from working. The reason this explanation is important is that certain normal cells, such as stem cells, need telomerase and this ability to function properly. There has been pause in the scientific community on the use of drugs that specifically target this enzyme given its vital role in the cell cycle. Rytelo is a telomerase inhibitor and binds to telomerase in order to reduce its ability to lengthen the ends of DNA (telomeres). By doing this, it attacks certain cells with active telomerase that are dividing and replicating frequently.

Rytelo's Approval

One of the last phases of clinical trial testing is called a phase III clinical trial . A phase III clinical trial tests the effectiveness and safety of a new treatment on a large group of people to confirm its benefits and monitor side effects. This type of trial is considered a "high evidence" study. Here, they compare a new drug to the current standard of care to see if it is better than what is already available. A phase III clinical trial often takes place at multiple hospitals across the country (or several nations) and involves hundreds of patients. The FDA approval of Rytelo is based on results from the IMerge phase III clinical trial, which were published in The Lancet Journal. The trial met its primary and key secondary end points, with the new drug demonstrating significantly higher rates of continuous red blood cell transfusion independence (meaning patients did not need to get red blood cell transfusions as often).

• 40% of patients (47 out of 118) in the Rytelo (imetelstat) group did not need a blood transfusion for at least 8 weeks
• 15% of patients (9 out of 61) in the placebo group did not need a blood transfusion for at least 8 weeks
• This difference was 25%, which is considered statistically significant

To summarize: more patients in the Rytelo (imetelstat) group avoided blood transfusions compared to the placebo group. And the difference between the two groups is statistically significant, meaning it's unlikely to be due to chance. “For patients with LR-MDS and anemia who are transfusion dependent, we have very few options today and often cycle through available therapies, making the approval of Rytelo potentially practice-changing for us,” said Dr Rami Komrokji , vice chair of the Malignant Hematology Department at Moffitt Cancer Center and an investigator of the pivotal IMerge clinical trial, in the news release. “What is exciting about Rytelo is the totality of the clinical benefit across LR-MDS patients irrespective of ring sideroblast status or high transfusion burden, including sustained and durable transfusion independence and increases in hemoglobin levels, all within a well-characterized safety profile of generally manageable cytopenias.” Rytelo is given through an IV every four weeks, fitting well with regular blood count checks for these patients.

Rytelo Safety and Side Effects

Although reducing how often patients with MDS need to undergo blood transfusions is a major advancement, like all cancer therapies, there is the potential for side effects. This new study found that Rytelo has a manageable safety profile, with some side effects that can be controlled. The most common serious side effects were:

• Neutropenia (low white blood cell count): 72% of patients.
• Thrombocytopenia (low platelet count): 65% of patients.

These side effects usually lasted less than two weeks and improved to milder levels in under four weeks for over 80% of patients. Other potential side effects included:

• Lower platelets, white blood cells, and neutrophils
• Increased liver enzymes (AST, ALT)
• Fatigue
• Prolonged blood clotting time
• Joint/muscle pain
• COVID-19 infection
• Headache
• Fever with low white blood cell count
• Sepsis
• Gastrointestinal bleeding
• High blood pressure

To manage side effects, a doctor may recommend adjusting the dose of medication given.

Blood Transfusion for Patients With MDS

To treat anemia, patients with MDS are sometimes given blood transfusions. During a blood transfusion, healthy donor blood is infused into the MDS patient via an IV. The process takes about two to three hours and the vast majority of patients feel much better after a blood transfusion. However, too many blood transfusions can cause unwanted side effects. If you get many transfusions over a long period of time, the iron in those blood transfusions can be deposited in your organs, potentially causing injury to some organs such as the liver, heart, and pancreas. That is why researchers are looking into other options for treating MDS  that will reduce the number of transfusions they might need. Dr. Jun Choi explains how blood transfusions are used to treat MDS.

What is MDS?

MDS is a variety of bone marrow disorders that look similar: under a microscope, the bone marrow cells look like cancer, and genetically may have alterations that are known to cause MDS. Symptoms of MDS include:

• Frequent infections
• Fatigue (lack of energy and exercise intolerance)
• Shortness of breath
• Low red-blood cells (anemia)
• Easy bleeding/bruising.

These symptoms are the result of the bone marrow not being able to produce enough healthy, functional blood cells. Because some patients with MDS will have their cancer evolve into Acute Myeloid Leukemia , it is important for your doctor to monitor risk. There are several ways to do do this, but doctors will look at:

• A patient's blood counts
• The amount of cancer in the bone marrow
• The presence of certain genetic abnormalities on the cancer cells

“For the workup of MDS, you start with a regular blood check and you confirm that someone has low blood cells,” Dr. Jun Choi , a hematologist/oncologist at NYU Langone’s Perlmutter Cancer Center told SurvivorNet in a previous conversation. “And then when the suspicion for MDS is high, the ultimate gold standard diagnostic test is a bone marrow biopsy. And that is because the bone marrow is where all the blood cells are made. And we want to confirm that there is abnormal cells in the bone marrow.” A bone marrow biopsy can confirm MDS. It can also provide other details on your cancer. “The biopsy has to be reviewed by the pathologist to see if there is what’s called dysplasia in the blood cells. Dysplasia is abnormal-looking young blood cells that we also want to send the bone marrow sample to assess for any genetic changes — and whether there is any abnormal changes in your chromosome, in the blood cells inside the bone marrow," Dr. Choi explained. "And based on those, we can categorize the MDS into different categories, different types, and ultimately they can also help us guide the treatments and the prognosis as well."

Questions to Ask Your Doctor

If you have MDS and anemia , here are some questions to consider asking your doctor to help understand your options:

• What risk level is my MDS? Is it low-risk?
• Are there tests available to assess my risk level?
• What treatment options can help reduce my need for blood transfusions?
• What is the benefit of reducing blood transfusions when treating myelodysplastic syndrome?
• Am I eligible for Rytelo?
• Are there side effects associated with Rytelo?