Combinations are the Future in FLT3-Mutated AML - Episode 10

Treatment Combinations in FLT3-Mutated AML


Experts in hematology comment on when it’s appropriate to use gilteritinib, particularly as a combination therapy, to treat patients with FLT3-mutated acute myeloid leukemia.

Naval G. Daver, MD: Let me ask you one question that I know you and some of your colleagues have worked on answering and have presented on at ASH [the American Society of Hematology annual meeting]—the use of gilteritinib in patients who had received a prior FLT3 inhibitor. We briefly mentioned that in both the QuANTUM-R and ADMIRAL studies, only between 5% and 10% or 11% of patients had received midostaurin or sorafenib with induction. So the question we get, and insurance companies have been asking this question as well, is, “Well, if you got midostaurin with induction, are the data still valid, the ADMIRAL data, and can you use it?” I know you had some data to suggest this.

Jessica K. Altman, MD: Thank you, and thank you for your participation in that study as well. It was a multicenter analysis. It’s the only way for us to capture enough patients to be able to study this. When we looked at patients who received 7+3 [cytarabine, daunorubicin] and midostaurin and then went on to receive gilteritinib and had a FLT3 mutation at both time points, it didn’t appear that prior midostaurin significantly impacted the response to gilteritinib. In fact, the response rate that we saw paralleled what was reported in the ADMIRAL study. So while there are all sorts of flaws with that type of study—it’s a retrospective analysis and at multiple academic centers who think about FLT3 all the time—we still found that the results are similar to what’s been reported with gilteritinib. So prior midostaurin use with 7+3 [cytarabine, daunorubicin] would not sway me from using gilteritinib at the time of relapse.

Naval G. Daver, MD: Yes, exactly. There were 2 other analyses, one by Alexander Perl, MD, looking at the ADMIRAL and CHRYSALIS trials and one from our group, and I think all of them pretty much have the same summary. The response rates with gilteritinib, or quizartinib, actually—we looked at quizartinib—may be a little bit lower in people who received prior TKIs [tyrosine kinase inhibitors], but they are in the same ballpark, between 40% and 55%. And the survival, especially when Dr Perl looked at patients who had received chemotherapy in salvage or gilteritinib in salvage, still showed that gilteritinib was better than chemotherapy. So I think there are 2 questions one can ask. One question is, in somebody who received prior midostaurin, is gilteritinib-based therapy still better than chemotherapy? I think the answer is yes. In people who received prior FLT3 inhibitors, is gilteritinib alone going to be enough? I think most of us would say no, and that’s probably true in general. I think that’s where the combinations of azacitidine and venetoclax and triplets will come in. But I think these should not be confused. I don’t think any of us are saying that you should not use gilteritinib. We’re saying you should use gilteritinib and something else, right?

Transcript Edited for Clarity