EHA 2021 | Imetelstat efficacy is independent of molecular subtypes in R/R LR-MDS
Valeria Santini, MD, University of Florence, Florence, Italy, shares an update on the Phase II/III IMerge study (NCT02598661) of imetelstat, a first-in-class telomerase inhibitor in patients with lower-risk, transfusion-dependent myelodysplastic syndromes (LR-MDS) who are relapsed/refractory (R/R) to erythropoiesis-stimulating agents. Dr Santini reports that all molecular subtypes of LR-MDS responded to imetelstat with no sensitivity differences between subtypes and no impact of the number of mutations on response. Dr Santini also gives an overview of the safety profile of imetelstat in LR-MDS. This interview took place at the virtual European Hematology Association (EHA) Congress 2021.
Transcript (edited for clarity)
My name is Valeria Santini, and I have been involved in the study with imetelstat in lower risk MDS, anemic and transfusion dependent. Now, imetelstat has shown a great activity in inducing transfusion independence because 42% of patients treated are indeed achieving the goal of stopping transfusion.
Now, what was interesting to see was that all molecular subtype of MDS were responding to imetelstat, without any particular subtype more sensitive than others...
My name is Valeria Santini, and I have been involved in the study with imetelstat in lower risk MDS, anemic and transfusion dependent. Now, imetelstat has shown a great activity in inducing transfusion independence because 42% of patients treated are indeed achieving the goal of stopping transfusion.
Now, what was interesting to see was that all molecular subtype of MDS were responding to imetelstat, without any particular subtype more sensitive than others. Now, the most important thing is that the number of mutations did not influence response. As a matter of fact, few patients, now this is a small cohort of 38 patients resistant to ESAs but having not received other treatment.
So, in this small group of patients, few had three or more mutations, but as we know the number of mutation correlates with overall survival. The number of mutation didn’t show any correlation with the response and type of response to imetelstat. Having said that, I have to stress the fact that the majority of patients included in the study had an SF3B1 mutation with other co-mutation or isolated, but they responded independently of the co-mutation and independently of the SF3B1. So, the patient did show indeed a good response rate.
That means that imetelstat, having a specific mechanism of action that is independent of the most frequent mutation alteration, or the alteration induced by the mutation, is an agent that can be used widely and independently of the mutational pattern of MDS as well as IPSS are low, very low or intermediate. So, I think it’s a very interesting agent.
And we also wanted to go back and evaluate the safety of this agent. Now, as, as you know, in myelofibrosis, there have been some warnings for a homoeopathic toxicity that was not observed in MDS patients. So, the main adverse event where the neutropenia and thrombocytopenia that were of low grade and were reversible, there were some increase in transaminases, but no hepatic toxicity in MDS. And overall, I would say that, generally imetelstat has a good profile. There are ongoing trials that will re-evaluate, even more profoundly, the adverse event and the toxicity of imetelstat, but this large evaluation in all myeloid malignancy treated with imetelstat did show that the most frequent, let’s say the most frequent adverse event for MDS was nausea and diarrhea. But otherwise, I mean the non-hematological, or otherwise very well-tolerated even in patient who received very long treatments.
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