Vijendra Singh: Why I’m skeptical about Imetelstat’s use for MDS treatment
Vijendra Singh, Medical oncologist at Karmanos cancer center, shared a post on X/Twitter:
”Why I’m skeptical about Imetelstat’s use for MDS treatment: Imetelstat is an oligonucleotide that inhibits telomerase activity by binding to the RNA template of telomerase.
Clinical trial: IMerge trial studied low or Int-1 risk MDS patients with anemia, who are refractory or ineligible to ESA and have greater than 4 PRBC transfusions over an 8-week period.
Dosing: Administered as a 2-hour infusion every 4 weeks.
Primary endpoint: 8 -week transfusion independence (TI):
- Imetelstat: 40%,
- Placebo: 15%.
Secondary and exploratory endpoints:
- 24-week TI: 28% vs. 3%,
- 1-year TI: 18% vs. 2%.
Molecular response signal observed with Imetelstat.
Only 7 patients had prior luspatercept exposure, none achieved 8-week TI with Imetelstat.
No improvement in patient-reported anemia symptoms or fatigue.
Side Effects:
- Grade 3-4 Neutropenia: 73% vs. 8%,
- G-CSF use: 36% vs. 3%,
- Infections: 47% vs. 34%,
- Sepsis: 4.2% vs. 0%.
More Side Effects:
- Grade 3-4 Thrombocytopenia: 65% vs. 8%,
- Platelet transfusion requirements: 18% vs. 2%,
- Bleeding: 22% vs. 12%.
Cytopenias had no correlation with erythropoietic response.
Other adverse effects:
- Fatigue: 29% vs. 22%,
- Myalgia/Arthralgia: 25% vs. 19%,
- Headache: 13% vs. 5%,
- Syncope: 6% vs. 1.7%,
- Pruritis: 6% vs. 1.7%,
- Fractures: 5% vs. 1.7%.
Does not seem this much toxicity is worth for such a marginal benefit, awaiting for some better dose response exploratory studies. Source.”
Source: Vijendra Singh/X