• Research is ongoing to find new treatments for myelodysplastic syndrome (MDS).
• Two new MDS medications were approved by the U.S. Food and Drug Administration (FDA) in 2020.
• Several promising new therapies are currently being studied in clinical trials.

Myelodysplastic syndrome is a group of conditions in which the body doesn’t make enough healthy blood cells. Stem cells, which are responsible for making all of the body’s blood cells, develop abnormalities in people with MDS, leading to too many immature blood cells and too few normal ones.

MDS is a form of cancer. Some people can live with MDS for many years. In other cases, MDS can turn into a more aggressive type of blood cancer, acute myeloid leukemia (AML). Doctors estimate a person’s outlook by determining their MDS risk score. People with very low-risk MDS have a 3 percent chance of developing AML within five years, while the chances for those with very-high-risk MDS are 84 percent.

People with higher-risk MDS do not have a very good health outlook. This highlights the need for more effective MDS treatments that can help people live longer and keep the condition under control. Additionally, even when treatments work well, they can take a toll on a person’s quality of life. For example, some people with MDS are treated with chemotherapy drugs, which come with many potential side effects.

In recent years, cancer researchers have made great strides in developing new MDS treatments that work more effectively than previously existing options. Research is ongoing, and treatment plans will likely continue to improve in the future.

Traditional Treatments for MDS

Traditionally, MDS has been treated with therapies including:

• Chemotherapy drugs that kill abnormal cells
• Drugs such as hypomethylating agents or lenalidomide (sold as Revlimid), an immunomodulatory drug
• Allogeneic stem cell transplant (also called a bone marrow transplant), a procedure in which the unhealthy cells are destroyed and new stem cells from a donor are delivered into the body
• Supportive care treatments such as blood transfusions or growth factors (molecules such as erythropoietin that help blood cells mature), which help reduce MDS symptoms

Newly Approved Medications for MDS

Newer therapies have recently become available. As researchers develop a new treatment, they conduct many laboratory tests and clinical trials to examine the treatment’s safety and effectiveness. They then submit their data to the FDA. If the FDA finds that a treatment’s benefits outweigh its risks, they approve it.

Treatments are approved for specific conditions and situations. For example, a medication may be approved only for the treatment of a specific subtype of MDS or a specific MDS risk group.

Reblozyl

Reblozyl (a formulation of luspatercept-aamt) is a targeted therapy drug that was approved by the FDA in April 2020. It can be used by people who have met all of the following conditions:

• Have been diagnosed with MDS with ring sideroblasts (MDS-RS) or with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis
• Have very low-, low-, or intermediate-risk disease
• Have tried using an erythropoiesis-stimulating agent (a type of supportive care) and found it to be ineffective
• Have needed red blood cell transfusions within the past eight weeks

Luspatercept is a laboratory-made protein. It attaches to and blocks certain proteins within the body that prevent red blood cells from maturing. Taking luspatercept can help red blood cells fully grow and carry out their normal roles within the body.

In a clinical trial, luspatercept helped improve the severity of MDS-RS, a low risk type of MDS. People with the condition who took luspatercept were more likely to no longer need blood transfusions, compared to people who did not take the drug.

Inqovi

Another newer MDS treatment is Inqovi (decitabine and cedazuridine). The FDA approved this drug in July 2020. It can be used by people who have tried other MDS drugs as well as people who have not yet undergone any treatments. The combination of decitabine and cedazuridine is approved for people with intermediate- or high-risk disease who have chronic myelomonocytic leukemia (or CMML) or the following types of MDS:

• Refractory anemia
• Refractory anemia with ringed sideroblasts
• Refractory anemia with excess blasts

Decitabine (sold as Dacogen) has been given to people with MDS for many years. It is a type of drug known as a hypomethylating agent — it can improve the function of certain genes that help blood cells grow more normally.

Combining decitabine with cedazuridine makes the drug easier to take. In the past, people who took decitabine usually received the drug through an IV. This required a person to travel to a clinic multiple days per month.

Decitabine alone can’t usually be taken by mouth, because it gets quickly broken down by the digestive system. However, cedazuridine blocks this process. Taking the two drugs together makes it possible for people to take a tablet form of decitabine at home.

In clinical trials, Inqovi caused signs of MDS to disappear temporarily in about 1 out of 5 people. Some people who used the drug also no longer needed blood transfusions.

Ongoing Research Into New MDS Treatments

Researchers are continuing to look into new medications, new drug combinations, and ways of improving traditional approaches like stem cell transplants.

Sabatolimab

Sabatolimab is a monoclonal antibody, a laboratory-made protein similar to the antibody proteins made by the immune system. The first drug in its class, sabatolimab received Fast Track designation from the FDA for adults with high or very-high-risk MDS. This label is given to medications that should be fast-tracked for research and development because they fill an unmet need for situations where no treatment currently exists. If the drug is fully proven, a regular FDA approval is given.

Sabatolimab binds to a target on immune cells and cancerous cells, but it does not harm the stem cells that form new healthy blood cells. In a recent clinical trial, some participants had a response to sabatolimab that lasted more than a year. Overall, 54 percent of participants with high-risk or very high-risk MDS and AML experienced an estimated 12 months of progression-free survival.

Magrolimab

Magrolimab is a monoclonal antibody, a laboratory-made protein similar to the antibody proteins made by the immune system. It blocks a protein called CD47, often found on cancer cells, which tells the body’s immune cells to leave the cancer cell alone. When CD47 is blocked by magrolimab, immune cells can more easily find and destroy cancer cells. Magrolimab can be used by people who were recently diagnosed with MDS.

Magrolimab is not yet approved by the FDA. However, the FDA has given the medication a Breakthrough Therapy designation. This is a process that helps drugs be developed and approved more quickly. The FDA awards a Breakthrough Therapy designation when early data shows that a drug may work much better than existing medications.

In an early clinical trial, more than 40 percent of people who took magrolimab plus azacitidine (sold as Onureg) had their signs of MDS disappear. Another clinical trial to study the effects of magrolimab is ongoing.

Imetelstat

Imetelstat is a telomerase inhibitor. It modifies cancerous stem cells and allows them to function more normally.

The FDA has given this drug a Fast Track designation for myelofibrosis, a type of MDS. This label is given to medications that should be fast-tracked for research and development and fill an unmet need for situations where no treatment currently exists. It is also being studied for other MDS subtypes.

Many people with lower-risk MDS have anemia (low red blood cell counts). They rely on blood transfusions in order to have enough red blood cells, but transfusions can lead to long-term health effects and a worse outlook. Imetelstat could fill an unmet need in MDS treatment by providing an alternative to getting regular transfusions.

In an early clinical study, more than 1 out of 5 people who took imetelstat were able to avoid needing blood transfusions for at least 24 weeks. Additionally, the drug reduced the number of cancer cells.

Eprenetapopt

This drug, also called APR-246, is designed to help people with MDS who have mutations in a gene called TP53. When cancer cells have certain variations in this gene, they can more easily avoid death. Eprenetapopt helps turn on a functional version of the gene, causing cancer cells to die.

Eprenetapopt has been given a Breakthrough Therapy designation as well as a Fast Track designation. In a small, early clinical trial, eprenetapopt combined with azacitidine led to promising results. In August 2021, the FDA placed a hold on the trial of this drug in combinations, due to safety and efficacy concerns. On Dec. 9, the FDA lifted the hold and the study resumed.

Genetic Research

Researchers are also studying the genetic causes of MDS. MDS develops when cells undergo gene changes that cause them to behave abnormally. Researchers now know that different gene mutations can cause different types of MDS, and are working to better understand these changes. This type of research could:

• Help doctors better estimate prognosis
• Allow doctors to more accurately determine which MDS treatments will be effective for each person
• Help researchers develop new treatments that can reverse the effects of specific gene changes

Choosing an MDS Treatment Plan

Not everyone who develops MDS receives treatment right away. However, your doctor may recommend starting treatment if you develop symptoms of MDS.

When deciding what treatment plan to recommend, your doctor will consider your risk score. If you have a higher risk score, you will likely need a more aggressive treatment approach. Risk scores are calculated using different scoring systems, such as the International Prognostic Scoring System. These systems take into account factors like:

• How many blasts (immature cells) are found in your blood
• How many cytopenias (low blood cell counts) you have, and which types of blood cells are affected
• How high your hemoglobin levels are (a protein found in red blood cells)
• What gene changes are found within your cancer cells

If you’re not happy with your current treatment options, you may be able to join a clinical trial. Researchers use clinical trials to test new medications, drug combinations, and procedures and determine the treatment’s efficacy (how well it works) and toxicity (what side effects it may cause). People who participate in clinical trials may be able to access new treatments that are not yet available as standard treatments.

If you’re ready to discuss treatment for MDS with your doctor, this discussion guide can help.

Talk With Others Who Understand

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