Cancer Conference Update: A Multimedia Review of Key Presentations from the 2016 American Society of Hematology Annual MeetingAbstract 449: Interim analyses of AMLSG 16-10 — Effect of age and midostaurin dose on response and outcome for patients with AML with FLT3-ITD mutations
5:02 minutes.
TRANSCRIPTION:
DR STEENSMA: So the big study that Rich Stone presented was an international trial in which patients with FLT3 activating mutations who were candidates for intensive chemotherapy — so they were age 18 to 60 — were treated either with standard induction alone or standard induction plus midostaurin. And there was a survival advantage to the midostaurin. There was a modest increase in complete response rate. And more patients who got the midostaurin were able to go on to transplant. Midostaurin is not currently FDA approved, but it is something that often we can get by compassionate use. And so for patients with FLT3-mutated disease, who are not trial candidates, we’re either giving them sorafenib — again, an off-label use, but it’s out there — or midostaurin if we can get it, to try to get them to respond in settings where there’s few other options. One of the problems with midostaurin, though, is that there’s a drug-drug interaction with posaconazole. And posa is increasingly used for patients with fungal disorders. And so this study looked at what dose was required in patients who were on strong CYP3A4 inhibitors, most commonly posaconazole. And they also looked at just what the pharmacokinetics were with the drug. And so this was not a large randomized study the way that the plenary session presentation last year by Rich Stone was, but it did again show that adding midostaurin to intensive chemotherapy was feasible. And there was not an impact of response on changing the dose, if you needed to, if the patient was on posa or another drug. And there was not a big difference based on the age of the patient. So that was really the key findings of this study. DR LOVE: Could you kind of capsulize your own recommendations to an oncologist in practice who’s going to treat a patient with AML, maybe an older patient, in terms of specifically what kinds of assays in terms of FLT3 should be done and what actions you think should be taken at this point based on the results? DR STEENSMA: Right. I think that’s an excellent question and a challenging one. Until recently, the NCCN Guidelines have really recommended doing 2 molecular assays, FLT3 and NPM1. And NPM1 is mostly seen in younger patients under age 60. I think there’s a lot of question about what other mutations are critical to assess, because many centers now, academic centers where large volumes of leukemia patients are treated, have their own panels that have 30 genes, 50 genes, 90 genes. And a lot of that, there may be many mutations that are not actionable. But there are some that I think do change what we do with the patient. Certainly FLT3 is one of those. Certainly IDH1 and IDH2, there are effective targeted agents that are in late-phase trials. And so I think it behooves us for our patients with AML to assay for those mutations, if not up front then at the time of relapse. I think p53 is important to know about, because if we see it, it affects the likelihood of success of transplant. And that may play into a patient’s decision, if they are a reduced-intensity transplant candidate, whether or not to do transplant. And also the data with the 10-day decitabine are fairly compelling. Again, the responses are not that durable, but high response rate. And so that might preferentially be something that you would do with the p53-mutant patients. So I think increasingly we’re seeing decisions that, in the past in AML, were based on is this patient an intensive therapy candidate or not? Is this patient a transplant candidate or not? Those are still key things, but now it’s is there a targeted agent available for their condition or do they have p53, which puts them in an extremely high-risk group, so that we should be thinking about other things? |