Mutation-Driven Therapy in MDS

*Please note: This slide show is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always consult your doctor about any questions you may have regarding a medical condition.

What is MDS?

MDS stands for "myelodysplastic syndromes." It is the name of a group of bone marrow failure disorders.

What is MDS?

In these disorders, the bone marrow does not produce enough healthy blood cells.

What is MDS?

Experts consider MDS a form of blood cancer. About 1 in 3 people with MDS eventually develops acute myeloid leukemia, or AML.¹

What is mutation-driven therapy for MDS?

Mutation-driven therapy is treatment based on the mutations, or changes, in your genes. Some of these, called driver mutations, help cancer develop.

What is mutation-driven therapy for MDS?

Knowing what mutations you have helps your doctor predict how your body will respond to MDS treatment. In fact, it can help them choose a treatment that targets your specific mutations.²

How can mutation-driven therapy help people with MDS?

People with MDS need better treatments. Right now, stem cell (bone marrow) transplant is the only treatment that can cure MDS. But many people with MDS are not healthy enough to have a transplant.

How can mutation-driven therapy help people with MDS?

Also, MDS has many different mutations. No single treatment works well for most people. Developing treatments that target the various  mutations, especially the most common ones, could help more people survive MDS.

Knowing your IPSS-R score

The IPSS-R is a scoring system that uses several factors to calculate the risk of MDS turning into AML or shortening your life. Your mutation profile can adjust the risk predicted by the IPSS-R. You may be considered to have lower or higher-risk MDS using this system.

Knowing your mutations leads to personalized MDS therapy

Certain mutations can change your risk even if your IPSS-R score is low. If you have certain mutations, you may not live as long as most people whose scores put them in a lower-risk group. You may not respond as well to treatment or may have an increased risk of developing AML.³

How is my outlook predicted in mutation-driven MDS therapy?

Experts now know that certain mutations, such as mutations of the TP53 gene, are associated with poorer outcomes from certain treatments.

These treatments can include specific chemotherapy drugs or even a stem cell transplant.

How is my outlook predicted in mutation-driven MDS therapy?

Knowing what mutations someone has can mean choosing other treatments or taking part in a clinical trial.³

This is just one example of how your mutation profile can help you and your doctor decide on treatment and predict how it may work.

What genes are most commonly mutated in MDS?

Some commonly mutated genes in people with MDS include SF3B1, DNMT3A, TET2, TP53, ASXL1, RUNX1, SRSF2, IDH1, IDH2, and U2AF1.⁴

People with some of these mutations seem to have very distinct characteristics to their MDS, and some, such as SF3B1, can be associated with a relatively good outlook.⁵

Mutation-driven targeted therapy versus chemotherapy

Mutation-driven therapies are treatments known to be more effective for people with certain mutations. In some cases, the therapy is targeted to treat the mutation that is driving MDS. This is more precise than most forms of chemotherapy.

Mutation-driven targeted therapy

In some cases, mutation-driven therapies can actually block the effects of the faulty genetic instructions that are preventing your body from making normal blood cells.⁴

How does mutation profiling affect a stem cell transplant?

Mutation profiling can tell your doctor how likely you are to benefit from a stem cell transplant, which is the only curative treatment for MDS.⁶

This is important because while a transplant can cure MDS, it also involves significant time and risk. If a challenging procedure may not benefit you, knowing this ahead of time can help you avoid choosing a treatment that is unlikely to work.

Where is MDS mutation-driven therapy going?

Today, your mutation profile is known to be very important for understanding your outlook, or prognosis, with MDS, and it can help you and your doctor make treatment decisions.

But the future involves using our knowledge of mutations in MDS to develop increasingly precise treatments that target specific driver mutations.

Where is MDS mutation-driven therapy going?

The International Working Group for Prognosis in MDS is one of these groups of researchers.⁴ This group is creating an MDS scoring system called the IPSS-M that includes the mutation profile. It allows for a more accurate MDS risk assessment than the IPSS-R doctors currently use.

Advocate to get tested

In the case of MDS, knowing what genetic mutations you have makes a big difference to treatment and outlook.

Your doctor should also order cytogenetic testing when diagnosing your MDS. This looks at the chromosomes, where DNA is stored, and adds to the information from mutation testing.

It can be important to repeat these tests later, as your cytogenetic and genetic mutation profiles can change.

If you are diagnosed with MDS, it is important to ask about this type of testing. Knowledge about your MDS-related genetics can lead to more successful treatment.

References

1. The Myelodysplastic Syndromes Foundation. What is MDS? Accessed March 4, 2022. https://www.mds-foundation.org/what-is-mds/
2. Platzbecker U. Treatment of MDS. Blood. 2019;133(10):1096-1107.
   https://ashpublications.org/blood/article/133/10/1096/272732/Treatment-of-MDS
3. Bejar R. Advances in personalized therapeutic approaches in myelodysplastic syndromes. J Natl Compr Canc Netw. 2019;17(11.5):1444-1447. https://jnccn.org/view/journals/jnccn/17/11.5/article-p1444.xml
4. The Myelodysplastic Syndromes Foundation. Understanding your MDS: Know your score, your subtype, and your mutation. [PDF]
   https://www.mds-foundation.org
5. Malcovati L, Stevenson K, Papaemmanuil E, et al. SF3B1-mutant MDS as a distinct disease subtype: a proposal from the International Working Group for the Prognosis of MDS. Blood. 2020;136(2):157-170.
   https://ashpublications.org/blood/article/136/2/157/454668/SF3B1-mutant-MDS-as-a-distinct-disease-subtype-a
6. Lindsley RC, Saber W, Mar BG, et al. Prognostic mutations in myelodysplastic syndrome after stem-cell transplantation. N Engl J Med. 2017;376(6):536-547.
   https://www.nejm.org/doi/10.1056/NEJMoa1611604