Imetelstat associated with rapid hematological responses in essential thrombocythemia

1. Imetelstat induced hematologic responses in 100% of essential thrombocythemia (ET) patients and prolonged treatment was associated with more gradual increases after the discontinuation of treatment.

2. All patients reported adverse events with imetelstat treatment. The most notable effects are neutropenia, elevated liver enzymes, fatigue, nausea, diarrhea, and dizziness.

Evidence Rating Level: 2 (Good) 

Study Rundown: ET, a myeloproliferative neoplasm, is associated with an increased risk of thrombotic complications, hemorrhagic complications, or both. It can transform into myelofibrosis or, in rare cases, can change into acute leukemia. Studies have shown that the telomerase inhibitor imetelstat competitively inhibits telomerase enzymatic activity.  This phase 2 study investigated whether imetelstat could elicit hematologic and molecular responses in patients with ET who had either refractory therapy to prior therapies or who had unacceptable side-effects from prior therapies. The study demonstrated that imetelstat induced hematologic responses in patients with ET in both groups. All patients demonstrated a hematologic response, and 89% had a complete hematologic response. The median time to complete a hematological response was 1.4 months. Patients that had longer treatment intervals showed a more gradual increase in platelet counts while patients that needed more frequent dosing had more rapid increases.

Click to read the study in NEJM

Relevant Reading: A Pilot Study of the Telomerase Inhibitor Imetelstat for Myelofibrosis

In-Depth [prospective cohort]: This was a phase 2, open-label, multicenter study with a total of 18 patients. Primary end point of the study included best overall hematologic response based on platelet response. Secondary end points included the frequency and severity of adverse events, the duration of hematologic response, the ELN “clinicohematologic” response, and the molecular response in patients with JAK2 V617F mutations, MPL W515L or MPL W515K mutations, or CALR mutations.

The overall rate of hematologic response was 100% (95% [CI], 83 – 100), and 89% had a complete hematologic response (95% [CI], 65 – 99). The lowest platelet counts were 261,000 per cubic millimeter at 23 weeks and 56,000 per cubic millimeter at 18 weeks, this trend did not sustain over the course of the study. Seven out of eight patients with JAK2 V617F mutations at baseline demonstrated a partial molecular response (88%; 95% [CI], 47 – 100; p=0.001). Adverse events were recorded in all patients. Neutropenia and abnormal liver-function tests were two of the main adverse events. The most common non-laboratory adverse events attributed to imetelstat were fatigue (83%), nausea (72%), diarrhea (78%), and dizziness (61%). 

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