Imetelstat Improves Outcomes in Heavily Transfusion-Dependent 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 most notable outcomes of the phase 2/3 IMerge trial (NCT02598661) of imetelstat (Rytelo) in patients with low-risk myelodysplastic syndrome (MDS).

The IMerge trial investigated imetelstat vs placebo with best supportive care with a primary end point of achievement of red blood cell transfusion independence of 8 weeks or longer. Brunner discusses how not only more than twice as many patients achieved transfusion independence, but patients who needed very frequent transfusions were able to significantly reduce the number of units needed. Additionally, some patients achieved a significantly longer duration of transfusion independence.

Finally, the variant allelic frequency (VAF) of certain mutations decreased in patients who received imetelstat, which could indicate the agent has disease-modifying effects. Brunner cautions that this could also be explained by changes in white blood cell count during treatment, but this aspect merits further examination of the mechanism of imetelstat.

TRANSCRIPTION:

0:10 | What they found was that patients treated with imetelstat had a higher transfusion independence rate. Approximately 40% of patients, roughly, 30-40% of patients achieved transfusion independence for at least 8 weeks. That was a comparison to the placebo, whereas around 15% of patients achieved transfusion independence. Notably patients who had very heavy transfusion dependence, patients who needed at least 6 units of blood every 8 weeks, they also benefited from the treatment with imetelstat. I think that's fairly unique if you're needing 6 units of blood over 8 weeks, that means you're coming in every few weeks, getting 1 to 2 units of blood. That's a pretty high burden on a given patient. To see a third of them or more get transfusion independence is a fairly unique thing for many MDS studies. They also found that that transfusion independence was durable a number of patients, [a] subset achieving at least 24 or even 52 weeks of transfusion independence.

1:21 | Another unique endpoint that was not really the primary end point of this study, but it's something that we're trying to use to better understand the role that imetelstat might play in treating transfusion-dependent MDS was that over treatment, we saw that the relative burden or the relative presence of certain mutations seemed to drop. Patients would have a decrease in the relative size of the mutations that were present, the VAF, variant allelic frequency. There's a lot of reasons that that can happen. Patients also had a decrease in their white [blood cell] count during treatment, and so sometimes that relative shift can change the VAF, but the fact that we saw this decrease really merits more close study of why this effect is happening, and that might give us some insight into, do we have a molecule that could modify disease in MDS?