A roundtable discussion on anemia management in myelodysplastic syndromes featuring moderator Guillermo Garcia-Manero, MD, of the University of Texas MD Anderson Cancer Center; Amy DeZern, MD, MHS, Johns Hopkins Medicine; Tiffany Tanaka, MD, of the University of California San Diego; and Uma Borate, MBBS, of Ohio State University.
The following is a transcript:
So let’s talk about some of the new drugs and some of the presentations at ASH to start. So what’s happening now? We have luspatercept, imetelstat we didn’t talk about the IDH1 inhibitor, but may not be 100% related to what we do.
But I think that a very important thing. So any other exciting drugs that are presented at the meeting or that are in development that you want to discuss.
I think there’s a lot of interest, and this excites me to continue to find ways to ameliorate the anemia, either in front line or later lines. And there’s an increasing emphasis on the inflammasome and the sort of just inflammatory milieu that exists in MDS. And so we have compounds that inhibin and LRP, and then elritercept, which is probably not right to call the second generation luspatercept, but it’s something that may have more activity in a similar mechanism of action.
So the in LRP inhibitor inflammasome inhibitor is oral, which is also quite appealing. And then … similar to luspatercept. So we’re gonna have options or maybe of other things I’ve missed that you guys mentioned.
I think another, well concern is not the proper word, but I’m thinking a little bit about this because now we have drugs that give you a 70% response upfront. Second line drugs. And we are like, clinical trialists, the four of us is like, how do you develop a drug in this context now and then? You know, you’re talking about the RP3 inhibitor.
Of course, we’re testing this in like fifth line low risk MDS. That actually is probably a very bad disease to have. And and the chances that there is activity in that particular context are probably minimal. And this happened with canakinumab that Uma has worked. So how do we do this? Actually, I think we should go to some type of combination.
But I’m actually starting to think, how do we now design the next generation of clinical trials? Because companies like really fast results right now it’s very tough. If we don’t know natural history of luspatercept failure ESA failure. And then how do we do this? I don’t know.
I think that’s a huge issue because you could be killing a very effective drug because you’re giving it too late and you want to give it earlier because that’s where it has the most benefit. But we don’t know how to design early intervention trials. I think there’s going to be a lot of discussion with the FDA, with sponsors, to find that right set of patients, because you don’t want to do any harm.
You don’t want to give a patient that feels relatively well because they may develop something in the future. And obviously I’m very passionate about this. I do think that if we can find that right balance, we may not be giving people all of these second and third line therapies that we’re all concerned about. We know, like giving somebody a telomerase inhibitor if we don’t know what it does.
But I agree with you, I, I don’t think we know how to do it. And I don’t want to kill good drugs by giving them in fifth line MD’s failure of everything as well.
Thinking about that, I wish we had more that were head to head. You know, it’s so easy to say and it’s just all about timing. But so many of these are placebo controlled. You know, even the, the new…
Thank you, that one is still placebo controlled. So how will we ever know how to sequence them? You know, I still think of the imetelstat as, like, a back pocket drug, but that’s probably wrong. But nevertheless, it’s been reassuring that it’s it has activity as a back pocket drug, but we’re probably doing it a disservice by thinking about it that way.
But until we have some actual head to head data, it’s hard to change that mindset.
