Cancer Conference Update: A Multimedia Review of Key Presentations from the 2016 American Society of Hematology Annual MeetingAbstract 1069: Final results of CHRYSALIS — A first-in-human Phase I/II study of the oral FLT3/AXL inhibitor gilteritinib (ASP2215) in relapsed/refractory AML
4:26 minutes.
TRANSCRIPTION:
DR STEENSMA: So one of the key questions in FLT3 inhibition is, how narrow do you want your kinase inhibitory activity to be versus having a kinase inhibitor like midostaurin that’s messy? Midostaurin/sorafenib, they, in addition to inhibiting FLT3, they also inhibit VEGF. There is inhibitory activity against protein kinase C. There’s some against KIT with midostaurin. In fact, midostaurin is quite useful in mast cell disorders. And it’s very possible that it will get FDA approval in mast cell disease before it ever does in FLT3 AML. We saw Jason Gotlib presented some very nice data in mast cell disease. That was published in The New England Journal with midostaurin in patients who had bad symptoms, C symptoms, from mast cell disease. So kinase inhibitors can be messy like that or they can be like this agent, gilteritinib, or like quizartinib or like crenolanib, all of which are moving forward in various trials, a much narrower but more potent FLT3 inhibitory activity. So this was a study of gilteritinib. And these studies have all had butterfly-related names. So this one is CHRYSALIS. And there’s a couple of others that I can’t remember exactly, MONARCH and some other trial names. And they enrolled 252 patients with relapsed/refractory disease. And many of them had had at least 2 AML therapies previously. And they could have either a FLT3 ITD mutation, which most of them had, or a point mutation at the 835 codon, D835. That’s the second-most frequent FLT3 activating change. And this started out with a dose escalation, and then it was a very large dose-expansion cohort. And the overall complete response rate was 11%. And then there were 30% additional patients who the blasts cleared, but the counts didn’t recover. That may still be useful, because that may then allow the patient to be bridged to another therapy — potentially even to a transplant, or for post-transplant relapses, to a donor lymphocyte infusion or a second transplant. But the drug was quite well tolerated. It does have, in some patients, a differentiation syndrome. I’m treating 1 patient right now who’s had a very peculiar response with a differentiating syndrome, but he is clearing his blasts. And so going forward, the dose that’s being tested in Phase III is 120 mg daily. And we’ll see. We’ll see where this agent shakes out with respect to other FLT3 inhibitors. DR LOVE: How do you think it’s going to shake out? DR STEENSMA: I think that it’s likely that some patients will respond better to 1 FLT3 inhibitor than another. And so we may even end up using these agents sequentially. So for instance, some of the clinical trials have allowed patients who were previously treated with sorafenib to go in and be treated with gilteritinib or quizartinib. And many of those patients have responded to the second FLT3 inhibitor. So I think that we may end up using these sequentially. But the real utility of FLT3 inhibition is probably going to be up front, the way the midostaurin story was done. You give intensive chemotherapy plus FLT3 inhibitor, or you give a hypomethylating agent plus FLT3 inhibitor for an older patient or someone who’d not likely tolerate 3 and 7. DR LOVE: Do you think at some point we’ll see randomized studies, 1 FLT3 inhibitor versus another? DR STEENSMA: I think that’s likely. |