Expert hematologist, Stephen Oh, MD, PhD, talks about unmet needs and promising new therapies in myelofibrosis.
Stephen Oh, MD, PhD: As far as unmet needs for patients with myelofibrosis, certainly, we recognize that we have made a lot of headway in helping patients with myelofibrosis with the newer agents that have become available. Patients now have the expectation that treatment with one of these drugs can provide symptom and spleen benefit. They feel better, and that's very important.
As far as what remains the greatest unmet needs, it's quite clearly a couple of things. Number one is the cytopenias. We have a number of agents that do seem to provide some degree of anemia benefits. It would be great if we had ways to completely ameliorate the cytopenias. That remains an unmet need, although there has been progress along those lines. The other is treatments or approaches that will result in a tangible improvement in overall survival. With some of these drugs, there have been data to suggest at least a modest improvement in overall survival, but we would like to see with some of these novel agents that they do impact overall survival.
That segues into the question of what new therapies are promising. I'll highlight a couple from this year's ASH [meeting]. One of the plenary session presentations was on a new antibody that is specific for mutant calreticulin. This is a major advance in the field in terms of designing and testing an antibody that is truly specific for mutant CALR. If the activity of the antibody is as expected, this could result in a quite potent clinical benefit because it would be specifically targeting the mutant cells. And that has come along with it the prospect for a molecular response that in a way has not been available with this kind of treatment thus far. The data that were presented looked very encouraging. We need to better understand exactly how this drug is working in the preclinical models, but it’s also certainly reasonable to go ahead and move forward to clinical trials in patients. I’m looking forward to seeing how data shakes out from that soon.
As far as other agents, there continues to be progress with several novel agents. I'll highlight a couple. With the BET inhibitor pelabresib, updated results were presented from the MANIFEST study focusing in large part on clinical correlates and biomarker analysis. We did have analysis that I presented concluding that bone marrow fibrosis changes in patients from the SIMPLIFY-1 study treated with momelotinib or ruxolitinib don’t correlate with clinical outcomes at all. However, with pelabresib, as a BET inhibitor or a different class of drugs, it is more believable or plausible that some of these biomarkers or other surrogates might be relevant for clinical outcomes. Looking at bone marrow fibrosis in isolation is probably not meaningful. But looking at other aspects of bone marrow morphology, the megakaryocyte declustering that was presented for that study, reductions in molecular markers, and things like that may altogether make a convincing case that one of these drugs, such as pelabresib, has the capacity to modify the underlying disease.
I'll take another minute to highlight some other exciting novel agents. We have multiple agents that are in phase 3 studies for myelofibrosis, including navitoclax, navtemadlin, and parsaclisib. All these agents, which all are different in terms of their mechanism of action are looking encouraging to varying degrees. The phase 3 results are critical to determine if they really will be approved for the treatment of patients with myelofibrosis. Then the correlated question will be how to use these agents potentially in combination with ruxolitinib or other JAK inhibitors, and then the timing of combining these therapies. It's an exciting and complicated time for the field with so many novel agents in development.
Transcript edited for clarity.