Transfusion Independence in Relapsed/Refractory MDS May Be Possible With Imetelstat

June 18, 2019
Virginia Powers, PhD

New data from the phase II/III IMerge trial show that imetelstat may allow for transfusion independence for patients with debilitating anemia caused by myelodysplastic syndrome,&nbsp;according to results presented at the&nbsp;2019 EHA Congress.<br /> &nbsp;

Pierre Fenaux MD, PhD

New data from the phase II/III IMerge trial shows that imetelstat may allow for transfusion independence for patients with debilitating anemia caused by myelodysplastic syndrome (MDS), according to results presented at the 2019 European Hematology Association (EHA) Congress.1

Treatment with single-agent imetelstat yielded an 8-week transfusion independence (TI) rate of 42% in heavily transfusion-dependent patients with MDS. These responses were durable, with patients showing a median duration of response (DoR) of 85.9 weeks (range, 8.0-140.9). Twenty-nine percent of patients achieved a 24-week TI. Furthermore, the mean relative reduction in red blood cell transfusion from baseline was 68%.

“Imetelstat is a first-in-class telomerase inhibitor that targets cells with short telomere length and active telomerase,” explained Pierre Fenaux MD, PhD, chairman of Groupe Francophone des Myélodysplasies, head of one of the hematology sections at Hôpital Saint Louis, and professor of hematology at Paris University.

Higher telomerase activity and shorter telomeres in the blood cells of some patients with lower-risk MDS are known to predict for shorter overall survival. Previously reported data have demonstrated clinical benefit with imetelstat in this patient population2;the agent has also been shown to have clinical activity in myelofibrosis.3

In the open-label, single-arm trial, investigators evaluated the efficacy of imetelstat in patients with lower-risk MDS. Specifically, the trial enrolled patients with low-risk, non-del(5q) MDS, who were relapsed or refractory to erythropoietin stimulating agents (ESAs) and had not been previously treated with lenalidomide or hypomethylating agents, which are not authorized in Europe for this indication.

The patients had a heavy transfusion requirement; 92% of patients (n = 35) had a baseline transfusion burden of more than 4 units every 8 weeks; the median transfusion burden was 8 units every 8 weeks (range, 4-14 units). The International Prognostic Scoring System (IPSS), which is based upon the percentage of leukemic blast cells in the marrow, the type of chromosomal changes in the marrow cells, and the presence of cytopenia was intermediate-1 (0.5-1) in 37% of patients (n = 14). Additionally, 71% of patients (n = 27) had WHO 2001 RARS or RCMD-RS subtype, and 32% of patients (n = 12) had baseline serum EPO levels >500 mU/mL. The patients were mostly men (66%; n = 25) with a median age of 71.5 years (range, 46-83 years). Prior EPO use was reported for 89% of patients (n = 34).

Imetelstat was administered intravenously at 7.5 mg/kg every 4 weeks for a median of 9 cycles to 13 patients in the initial cohort and 25 patients in the expansion cohort. The 8-week TI rate served as the primary endpoint of the trial, while the key secondary endpoints included 24-week TI rate, safety, duration of TI, and the hematologic improvement (HI) rate, which was defined as transfusion reduction of at least 4 units every 8 weeks.

Overall, median follow-up was 12.1 months for the 38 patients; however, follow-up was 30.4 months in the initial cohort and 11.6 months in the expansion cohort.

Five (13%) patients achieved a complete response (CR) with 4 (10%) patients showing a CR in the marrow; this translated to an overall CR rate (CR + marrow CR) of 24% (n = 9). No partial responses were observed.

The presence of ring sideroblasts or baseline serum erythropoietin levels did not affect the 8-week TI rate.

Erythroid hematological improvements were seen in the majority of patients (68%; n = 26) as early as 8 weeks into treatment, and 32% of patients (n = 12) experienced an increase in hemoglobin of 1.5 gr/dL that lasted for 8 weeks or more.

Moreover, of the 16 patients who achieved 8-week TI, a high rise from baseline of 3g/dL was observed in 75% of patients (n = 12).

In a subgroup of 6 patients with IPSS-R intermediate or poor cytogenetic risk, all patients achieved 8-week TI, while 2 patients showed partial cytogenetic response.

The most frequently reported adverse events were determined to be manageable and reversible, including grade ≥3 cytopenia. No liver toxicity was observed.

“Single agent imetelstat provided meaningful and durable transfusion independence in patients with a high red blood cell transfusion burden and non-del(5q) lower-risk MDS who were relapsed or refractory to ESA,” Feneaux said.

“Transfusion independence was observed across different clinical subgroups, including patients with intermediate and poor cytogenetic risk; in fact, patients with a poorer prognosis showed better response, suggesting that the drug could translate to treatment of higher risk MDS patients,” he added. “These findings support part 2 of IMerge. We also plan to evaluate imetelstat in patients with higher-risk MDS.”


  1. Fenaux P, Steensma DP, Eygen KV, et al. Treatment with imetelstat provides durable transfusion independence (TI) in heavily transfused non-del(5Q) lower risk MDS (LR-MDS) relapsed/refractory (R/R) to erythropoiesis stimulating agents (ESAS). Presented at: 2019 European Hematology Association Congress; June 18-22, 2019; Amsterdam, Sweden. Abstract S837.
  2. Steensma DP, Platzbecker U, Eygen KV, et al. Imetelstat treatment leads to durable transfusion independence (TI) in RBC transfusion-dependent (TD), non-del(5q) lower risk MDS relapsed/refractory to erythropoiesis-stimulating agent (ESA) who are lenalidomide (LEN) and HMA naive.Blood. 2018;132:463. doi: 10.1182/blood-2018-99-114877.
  3. Tefferi A, Lasho TL, Begna KH, et al. A pilot study of the telomerase inhibitor imetelstat for myelofibrosis.N Engl J Med. 2015;373(10):908-919. doi: 10.1056/NEJMoa1310523