Imetelstat Shows Limited Early Efficacy in Advanced MDS and AML: Interim Results From the IMpress Study

Initial findings from the IMpress trial indicate that imetelstat, the first FDA-approved telomerase inhibitor for lower-risk myelodysplastic syndrome (MDS), demonstrated minimal efficacy in higher-risk MDS and acute myeloid leukemia (AML) in patients for whom standard therapies failed, prompting protocol adjustments for future cohorts.

Hypomethylating agents (HMAs), either as monotherapy or in combination with venetoclax, represent the standard of care for patients with higher-risk MDS or AML who are not candidates for intensive chemotherapy or allogeneic stem cell transplantation. Unfortunately, a significant number of patients either fail to respond or experience relapse, leaving this patient population with limited options.

Uwe Platzbecker, MD, University of Leipzig Medical Center, Leipzig, Germany, presented the preliminary results of a multicenter, phase II trial, led by the European Myelodysplastic Neoplasms Cooperative Group (EMSCO), evaluating imetelstat’s potential to address this critical unmet need: treatment-resistant higher-risk MDS and AML.¹ Imetelstat, a telomerase inhibitor approved for transfusion-dependent lower-risk MDS, was explored for its efficacy and safety in higher-risk MDS and AML.

In this first trial phase, 23 patients (17 with AML and six with higher-risk MDS) in Germany, France, and Australia received imetelstat, 7.5 mg/kg, every 4 weeks. After two cycles, disease response assessments revealed that only one patient had achieved hematologic improvement; seven exhibited stable disease, and eight experienced progression. Short-term declines in leukocyte and blast counts suggested limited antiproliferative effects, but no patient reached the study’s stringent primary endpoint of significant response after four months of treatment.

The study recorded 30 serious adverse events in 18 participants, including infections, febrile neutropenia, and disease progression. Ten serious adverse events resulted in death, although only one (pneumonia) was deemed potentially related to the drug. No unexpected safety signals were observed.

“Based on the observations in this first cohort,” said Dr. Platzbecker, “the protocol was amended to a more frequent dosing schedule, with imetelstat every two weeks for at least the first four cycles.” The limited responses observed in this preliminary analysis reflect the inherent challenges of managing refractory disease and highlight the continued unmet need for novel treatments in this challenging patient population.

Reference

1. Platzbecker U, Lane SW, Garnier A, et al. A phase II study evaluating the efficacy and safety of imetelstat in patients with advanced myelodysplastic neoplasms or AML failing HMA-based therapy – interim analysis results of the Impress study. Abstract #3222. Presented at the American Society of Hematology Annual Meeting; December 7-10, 2024; San Diego, California.