 Department of Hematology, associate clinical professor, Faculty of Medicine, Clínica Universidad de Navarra, Pamplona, Spain, discusses unmet needs for patients with high-risk myelodysplastic syndrome (MDS).

Patients with MDS are generally categorized as having either higher-risk (HR) or lower-risk disease according to clinical prognostic scoring systems. HR-MDS is more common in patients who are 70 years of age or older, Alfonso Piérola begins. This makes patients with HR-MDS particularly challenging to treat, as advanced age is associated with a higher incidence of comorbidities and increased adverse effects (AEs), Alfonso Piérola explains.

In addition to challenges associated with MDS treatment, there is a significant need for expanding the number of approved therapeutic options in this space, Alfonso Piérola continues. The hypomethylating agents (HMAs) decitabine and azacitidine are both approved by the FDA as a first-line treatment for patients with MDS regardless of disease risk. However, only azacitidine is approved for this population in Europe, Alfonso Piérola notes.

Many other agents have been investigated in phase 3 trials since the approval of azacitidine, but they failed to demonstrate any survival benefit and often resulted in greater toxicities, Alfonso Piérola adds. However, several newer investigational combinations have shown encouraging early activity in HR-MDS, Alfonso Piérola says. These consist of an HMA plus either an immunotherapy agent, the oral selective retinoic acid receptor alpha (RARα) agonist tamibarotene, or the BCL-2 inhibitor venetoclax (Venclexta).

Tamibarotene received fast track designation from the FDA

 for the treatment of patients with HR-MDS in January 2023. The agent is being evaluated further in combination with azacitidine in the phase 3 SELECT-MDS-1 trial (NCT04797780) in newly diagnosed RARA-positive, HR-MDS. Phase 3 results are still needed to confirm the benefit of these approaches, but investigators hope for new approvals based on such data in the near future, Alfonso Piérola concludes.

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Ana Alfonso Piérola, MD, PhD, discusses unmet needs for patients with high-risk myelodysplastic syndrome.


Ana Alfonso Piérola, MD, PhD

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Dr Alfonso Piérola on Unmet Needs in Higher-Risk MDS