How Higher Doses of Imetelstat May Benefit Patients with Relapsed/Refractory Myelofibrosis

In an interview with CURE®, lead study investigator Dr. John Mascarenhas discusses what the results of the phase 2 IMbark study could mean for the future of patients with myelofibrosis.

For patients with myelofibrosis who relapsed or are refractory to treatment, Janus kinase (JAK) inhibitor therapy elicited a better overall survival response, spleen response and symptom response when higher doses of the telomerase inhibitor imetelstat were added to treatment, according to Dr. John Mascarenhas.

In a presentation at the 2020 ASH Annual Meeting and Exposition, Mascarenhas discussed the benefits of this drug based off the analysis of the phase 2 IMbark study that looked to evaluate the efficacy of higher doses of imetelstat given intravenously to patients with myelofibrosis who experienced complications after previous treatments. Survival, symptom response, spleen response and overall fibrosis improvement were the endpoints of the analysis, which Mascarenhas explained were all superior in the higher dose arm of imetelstat.

In an interview with CURE®, Mascarenhas further explained the spleen and symptom response from this trial and how it not only fits in the overall treatment landscape for patients with myelofibrosis but where it could lead treatment in further trials.

Transcription:

Mainly because JAK inhibitors set the stage, we've really been focused on spleen response and symptom benefit, which are not unimportant, they are important. It is important to improve quality of life of our patients and reducing spleen response and symptoms has shown to do that and JAK inhibitors are quite adept at doing that. There's a number of JAK inhibitors, either that are approved, like Jakafi (ruxolitinib) and fedratinib (Inrebic), which are excellent drugs, and do achieve those goals in the majority of our patients. And there are a number of JAK inhibitors that are in clinical development, that hope to fill very special niches like pacritinib for low platelets for those patients who have transfusion dependent anemia.

However, what is distinct and important about imetelstat not just from a clinical investigator standpoint who cares for these patients, but for patients themselves, is the idea that we're moving the field forward. It is not simply affecting aspects of the disease, like spleen and symptom which are disease features and clinical characteristics, but also trying to change the natural history and outcome of this disease. And again, we know that in patients who failed Jakafi, the outcome can be poor and patients can do poorly, particularly patients who have low platelets either at the on start of Jakafi, or at the time of discontinuation or those that develop clonal evolution that develop mutations like AXSL1 while taking a JAK inhibitor.

So, it is really an unmet need in this field to try to improve the survival of patients who are failing or failed, Jakafi. What I'm hopeful for is that this drug will meet that, but it's not that simple. It has to be proven in a clinical trial and it has to be balanced with the fact that the drug is an intravenous drug. It's administered every three weeks and it is associated with a certain degree of myelosuppression or lowering of blood counts. So, it may not be for every patient, but for certain patients it may be a way to increase their survival, and in some cases, maybe even bridge patients to definitive therapy, like bone marrow transplant.

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.