Imetelstat in Lower-Risk MDS With High Transfusion Dependence

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In the phase II portion of the phase II/III MDS3001 study reported in the Journal of Clinical Oncology, David P. Steensma, MD, and colleagues found that imetelstat—a first-in-class competitive inhibitor of telomerase enzymatic activity—markedly reduced the need for red blood cell transfusion in patients with lower-risk myelodysplastic syndromes (MDS) and high transfusion dependence.

Study Details

The study enrolled 57 patients with MDS who required four or more red blood cell units transfused over an 8-week period during the 16 weeks before study entry and who relapsed after or were refractory to an erythropoiesis-stimulating agent. Of these, 38 had non-del(5q) MDS and had not received a hypomethylating agent or lenalidomide (subset population). All patients received imetelstat at 7.5 mg/kg via 2-hour infusion every 4 weeks until disease progression, unacceptable toxicity, or lack of response.

David P. Steensma, MD

David P. Steensma, MD

The primary endpoint was 8-week red blood cell transfusion independence. At clinical cutoff in April 2019, median follow-up was 16.4 months in the overall population and 15.7 months in the subset population. 

Transfusion Independence

In the overall population, rates of red blood cell transfusion independence were 37% and 23% at 8 and 24 weeks. The duration of transfusion independence was 65 weeks (range = 17–140.9 weeks). In the subset population, rates of transfusion independence were 42% and 29% at 8 and 24 weeks, with a median duration of transfusion independence of 86 weeks (range = 8.0–140.9 weeks). Rates of transfusion independence at 8 weeks did not differ according to baseline red blood cell transfusion burden (≤ vs > 6 units), presence of ringed sideroblasts, or baseline serum erythropoietin level (≤ vs > 500 mU/mL).


  • Among all patients, imetelstat treatment resulted in transfusion independence in 37% and 23% of patients at 8 and 24 weeks.
  • Among patients who had non-del(5q) MDS and were hypomethylating agent– and lenalidomide-naive, respective rates were 42% and 29%.

Cytogenetic analysis showed a reduction in malignant clones in some patients (eg, in del[5q] and trisomy 8). Mutational analysis showed reductions in SF3B1 variant allele frequency in 10 of 11 evaluable patients (with greater reduction being associated with longer transfusion independence) and variant allele frequency reductions in several other genes in some patients. These findings suggest a potential disease-modifying activity of imetelstat treatment.

Adverse Events

The most common grade 3 or 4 adverse events among all patients were hematologic, including neutropenia in 60% of patients, thrombocytopenia in 54%, and anemia in 19%; median durations were 1.7 weeks for neutropenia and 1.1 weeks for thrombocytopenia, with 90% and 88% of events resolving to grade ≤ 2 within 4 weeks. The most common nonhematologic grade 3 or 4 adverse events were back pain, increased alanine transaminase, increased aspartate transaminase, and bronchitis (5% each). 

The investigators concluded, “Imetelstat treatment results in a meaningful, durable transfusion independence rate across a broad range of heavily transfused patients with lower-risk MDS who are ineligible for or relapsed/refractory to erythropoiesis-stimulating agents. Biomarker analyses indicated effects on the mutant malignant clones.”

Dr. Steensma, of the Division of Hematological Malignancies, Dana-Farber Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was funded by Geron Corporation and Janssen Research & Development. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.