Understanding the Importance of Transfusion Independence in MDS

Andrew M. Brunner, MD, assistant professor of medicine at Harvard Medical School and at the Center for Leukemia at Massachusetts General Hospital in Boston, Massachusetts, discusses the current challenges and progress in identifying effective therapies for patients with transfusion-dependent myelodysplastic syndromes (MDS).

Biomarkers such as ring sideroblasts are indicators for response to treatments like luspatercept (Reblozyl). In patients with SF3B1 mutations, imetelstat (Rytelo) has shown response. Brunner underscores the importance of distinguishing between patients whose primary symptom is red blood cell transfusion dependence and those with other problems.

While only a minority of treated patients with MDS achieve complete transfusion independence, many maintain durable remission, which is crucial for patients expected to live with the disease for years, according to Brunner. He also emphasizes the goal of extending treatment durations to prevent complications from repeated red blood cell transfusions and to avoid progression to higher-risk MDS or acute leukemia.

TRANSCRIPTION

0:10 | I think we’re still figuring out how best to treat patients who have transfusion dependent MDS, and we have some sense of biomarkers, but they’re not precise. Ring sideroblasts, for instance, those have come out as markers for response to luspatercept. They were also the group, SF3B1-mutant patients, [who] seem to respond with imetelstat. Is there something about that biology that’s more sensitive, or are we finding patients [for whom] red cell transfusion independence is their primary problem, and we’re treating that? I think we’re still figuring that out.

0:44 | What is striking to me is that while it’s still a minority of patients [who] achieve true transfusion independence, many of those patients went on to have very durable transfusion independence periods. In a disease where you’re really thinking about patients living multiple years during your treatment, typically having just progressive low blood counts, and for many patients, particularly SF3B1, they will just coexist with their disease and have red cell transfusion dependence for a long time. It has a relatively low rate of progression to higher-risk MDS or acute leukemia. And so, if you can find therapies that can extend the treatment lifetime for each one, you can really keep a patient transfusion independent for longer and avoid the complications that can arise as people get red cell transfusion overload.