ASH 2025 | An upcoming Phase II trial of eltrombopag in low-risk MDS and CMML harboring TET2 mutations

So low-risk MDS and low-risk CMML is characterized by low blood counts, anemia, thrombocytopenia, leukopenia, neutropenia, and then the patients are at increased risk of bleeding, they’re at increased risk of infections, and time spent in hospitalization. So the goals of treatment in low-risk MDS and CMML are to improve these cytopenias, to make our patients transfusion independent, and to improve their quality of life. So far, there’s not a whole lot of strategies that are focused on mutations specifically to work on these CBC parameters to improve the cytopenias. So, there was a bench or a lab discovery that happened at Cleveland Clinic where we noted that eltrombopag, which is a drug that’s a TPO receptor agonist, thrombopoietin receptor agonist, used for ITP, but we found in a functional drug screen and in preclinical models as well, that this drug can be synthetically lethal to specifically TET2 mutant cells. And that was the motivation to design this investigative initiative trial for low-risk MDS and low-risk CMML patients with the understanding that those who have this TET2 mutation, the TET2 mutant cells will die while preserving the normal hematopoietic stem cell compartment. So this is a Phase II study that will look at 25 patients, enrolling 25 patients and then we’ll be looking at their hematological responses and then as a correlative we’ll be looking at TET2 mutation burden and some other correlatives like 5-mC and 5-hmC levels and changes that happen from there on.

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