Cancer Conference Update: A Multimedia Review of Key Presentations from the 2016 American Society of Hematology Annual MeetingAbstract 1070: Isocitrate dehydrogenase 1 (IDH1) mutational burden and clearance in patients with IDH1 mutation-positive acute leukemias receiving the first-in-class inhibitor of IDH1 AG-120
4:16 minutes.
TRANSCRIPTION:
DR STEENSMA: So there’s a couple of IDH inhibitors that are fairly far advanced. AG-120 is an IDH1 inhibitor. And AG-221 is an IDH2 inhibitor. There are others that are moving forward, but they’re at an earlier stage. Both of these agents have about an 18% complete response rate, which is not that high. But many other patients do have blast reduction or stability of disease for a prolonged period of time. And this particular report was about AG-120 in IDH1-mutant acute leukemias. And they looked at what happened to the IDH mutation with therapy over time. And there were a couple of patients that were presented. One of them is one of my own patients who had very long and very durable responses, where the IDH mutation became no longer detectable or was only detectable at a very low level, at a very low frequency. Now, one of the things that we’re learning as we go along is that when patients do relapse, they may relapse with a subclone of leukemia cells that doesn’t have an IDH mutation anymore. So, for instance, my patient, who had more than 2 years of a nice response to this compound, has now relapsed with a clone of cells that don’t have an IDH mutation. They have an SF3B1 mutation, a splicing mutation driving them. And so that may be what we see in a subset of patients who are treated with this for a prolonged period. But I think the take-home message from this abstract was that the reduction that we see in blast cells with this agent, in many cases, is accompanied also by a clonal reduction, by a decrease in the mutant allele burden, and that that may be durable in some patients. DR LOVE: What fraction of patients with AML have this mutation? DR STEENSMA: So if you look at IDH1 and IDH2, it’s about 25% to 30%. IDH2 mutations are more common. So this one is more in the 5% to 10% range. DR LOVE: And again, where do you see agents like this fitting in? Or do you see them coming into practice? And if so, how soon? DR STEENSMA: So there are ongoing trials of these agents in addition to chemotherapy and in addition to hypomethylating agents, so I think if you have a patient who has one of these targetable mutations, then this is going to be your drug that you’re going to want to add to a chemotherapy backbone. Right now, it’s largely patients who are getting these out — it’s people with relapsed/refractory disease. But now these are being moved up front. DR LOVE: Now, your patient with the relapsed disease, sounds like, has benefited from this therapy. DR STEENSMA: Absolutely. I mean, he and his family are incredibly grateful, because it really gave him an extra 2 and a half years that almost certainly he wouldn’t have had otherwise. DR LOVE: And this was monotherapy? DR STEENSMA: This was monotherapy. DR LOVE: Any tolerability issues with the drug? DR STEENSMA: Absolutely none for him. Yes. There have been patients who’ve had problems with edema or with GI upset or headaches. Some of these types of things happen, but my patient was able to be fully functional. He’s a big cook. He made a huge Sicilian dinner at Christmastime. It was just really great to see. DR LOVE: In an era we see so many trials for so long now, where you add something to an efficacious therapy, you can’t really figure out what’s going on or it’s not that easy. You don’t have to hear too many cases like this one to go, “Hey, why don’t I have this available?” DR STEENSMA: Right. DR LOVE: But I guess we’ll see. DR STEENSMA: Right. Hopefully we will, because there are patients right now who have an IDH mutation who can’t get on a trial, because there’s no trial for them. So I hope these agents get approved soon. |