EHA 2023 | Current and emerging treatment options for LR-MDS-associated anemia following ESA failure
Matteo Della Porta, MD, Humanitas University and Research Hospital, Milan, Italy, discusses the current and emerging treatment options for patients with lower-risk myelodysplastic syndromes (MDS)-associated transfusion-dependent anemia who fail ESA treatment. Prof. Della Porta explains how these treatments differ depending on patient subtypes, such as those with the 5q deletion, or those with ring sideroblasts, and highlights the emerging role of imetelstat in this setting. This interview took place at the 28th Congress of the European Hematology Association (EHA) 2023 in Frankfurt, Germany.
These works are owned by Magdalen Medical Publishing (MMP) and are protected by copyright laws and treaties around the world. All rights are reserved.
Transcript (edited for clarity)
Patients with low risk MDS and transfusion-dependent anemia who failed treatment with ESA, we have some therapeutical options. For patients with 5q deletion, lenalidomide is associated with a large clinical benefit in a very high proportion of patients that became again transfusion independent. In patients with ring sideroblasts, the most relevant treatment in terms of achieving a clinical benefit is a luspatercept, that is now approved for this patient category, that is patients with ring sideroblasts with transfusion-dependent anemia after ESA failure...
Patients with low risk MDS and transfusion-dependent anemia who failed treatment with ESA, we have some therapeutical options. For patients with 5q deletion, lenalidomide is associated with a large clinical benefit in a very high proportion of patients that became again transfusion independent. In patients with ring sideroblasts, the most relevant treatment in terms of achieving a clinical benefit is a luspatercept, that is now approved for this patient category, that is patients with ring sideroblasts with transfusion-dependent anemia after ESA failure. And according to both the results of the randomized Phase III MEDALIST trial as well as from the real-life patient population, we can state that 30-40% of the patients may achieve transfusion independence. For those patients without 5q- or ring sideroblasts, we have quite limited options, most including hypomethylating agents. But however, the approval of this drug depends on different countries and different regulatory agency. For instance, in Europe, there is no approval to use hypomethylating agents in low risk MDS, and for this reason, only a minority of the patients is eligible.
The personalized treatment of a transfusion-dependent anemia in low risk MDS after ESA failure also includes the emerging role of newer drugs. One example is imetelstat, that is a very specific drug that targets and inhibits telomerase enzyme activity in bone marrow progenitors, thus improving ineffective hematopoiesis. And in a recent Phase II/III study, imetelstat in a population of low risk MDS who failed or relapsed after ESA treatment was able to induce a clinical benefit in 37% of treated patients, the clinical benefit was achieved and defined as a transfusion independence for at least eight weeks. The mechanism of action of imetelstat is quite different with respect to that of luspatercept, and imetelstat seems to be a drug that is able to modify the MDS clone as demonstrated by the observation of a reduction of variant allele frequency of SF3B1 mutation in patients with ring sideroblasts that achieved a clinical benefit. So overall, there are emerging drugs that can improve our capability to face the unmet clinical need of low risk MDS patients with the transfusion-dependent anemia after ESA failure.
Read more...
