Phase 2 imetelstat telomerase inhibitor in MDS/MPN overlap syndromes and CMML.

This Phase 2, single-arm MD Anderson study tests imetelstat, a first-in-class telomerase inhibitor (an oligonucleotide that binds the telomerase RNA template to block telomere maintenance), given by IV infusion every 4 weeks, to see if it can control myelodysplastic/myeloproliferative neoplasms (MDS/MPNs) and chronic myelomonocytic leukemia (CMML). It enrolls several high-need subgroups, including MDS/MPN with SF3B1 mutation with thrombocytosis (historically MDS/MPN-RS-T), MDS/MPN with neutrophilia or MDS/MPN-NOS with elevated marrow blasts, and CMML-1/2 with inadequate benefit or intolerance to prior therapies such as hydroxyurea and/or hypomethylating agents (azacitidine or decitabine) depending on subtype. Scientifically, it extends a telomerase-targeting approach beyond lower-risk MDS—where imetelstat previously showed clinically meaningful transfusion-independence in a randomized Phase 3 program that supported FDA approval—into overlap/CMML populations with limited options after standard cytoreduction and epigenetic therapy fail.