Although there have not been many new approvals in the treatment of high-risk MDS, we really are starting to evolve in how we approach that disease entity, both in clinical trials, but also just in our greater understanding of the molecular behavior of a disease and also our understanding of some of the dynamics of disease that we’ve somewhat borrowed from AML. I think that for many patients with MDS, what was known before is all the more clear, that transplant candidacy is a critical first step in assessing a patient...
Although there have not been many new approvals in the treatment of high-risk MDS, we really are starting to evolve in how we approach that disease entity, both in clinical trials, but also just in our greater understanding of the molecular behavior of a disease and also our understanding of some of the dynamics of disease that we’ve somewhat borrowed from AML. I think that for many patients with MDS, what was known before is all the more clear, that transplant candidacy is a critical first step in assessing a patient. For us, we really try to have almost all of our patients assessed by our transplant team because numeric age, for instance, is much less a barrier than it was in the past. It’s much more important to give patients a chance for evaluation because that’s really the best long-term treatment for most patients with MDS.
For those that aren’t transplant candidates, we’re still using hypomethylating agents primarily. And even for those who are, they may need some degree of cytoreduction before. I think there is a little bit of nuance that’s starting to emerge in MDS. One of those areas is molecularly driven therapies. Now, really we only have those that are largely more studied in AML, but the few patients with MDS with a mutation in IDH1, IDH2, or FLT3, sometimes those can be incorporated into early or later lines of therapy.
And then thinking about some disease entities as perhaps being more AML-like, I think a good example is NPM1 mutations in MDS. Again, although uncommon, they do respond very well to AML-like therapies, such as induction or azacitidine and venetoclax. And so while I determine whether or not somebody is a transplant candidate and prepare them for that undertaking, I’m also often thinking about some degree of treatment having methylating agents being our standard backbone, but with a lot more variation, perhaps depending on the molecular profile and also on the intent of the treatment for the patient. I think what we hope will happen is that that becomes even further nuanced if we get some agents that have, for instance, a clear improvement in overall response rate, compared to azacitidine monotherapy, perhaps we’ll want to get better response before something like a transplant or a survival benefit for azacitidine that would also influence how we treat patients. And I’m hoping that some of the Phase III studies that are underway will shed light on possible future avenues to that regard.