ISAL 2023 | Insights into the treatment of patients with FLT3-mutated AML & the role of maintenance therapy

For a chemo fit AML patient who walks in the door, in most places in the world today, they’re going to get induction therapy with 3+7 or daunorubicin cytarabine plus midostaurin, based on the now six-year old results of the RATIFY trial, which showed that adding midostaurin to chemotherapy improved the outcomes in terms of survival compared to chemotherapy alone when it’s used with chemotherapy during induction, with chemotherapy during consolidation, and maintenance. Now most patients with FLT3-mutant AML are going to get a transplant in first remission. So the issue of whether it should be given with consolidation or maintenance is a little bit less important, if you will. But for those patients who aren’t going to get a transplant, the RATIFY trial did suggest that using midostaurin maintenance was a good idea, although there was no separate randomization. So in point of fact, we really don’t know that to be the case. Ironically, midostaurin was approved as a maintenance therapy in Europe but not in the US. So it’s still a bit of an unsettled area. I think a more interesting question is what FLT3 inhibitor, if any, should be given to a patient who underwent a transplant in first CR. The results of the MORPHO trial are a randomization of gilteritinib versus nothing in FLT3 patients who received the transplant in CR one. It was just presented in the form of a press release suggesting that it did not meet its primary endpoint, but that it was very close to meeting it. So I think we really need to wait for the full paper before we come to any conclusions about that. So in summary, there should be a FLT3 inhibitor, either midostaurin or possibly quizartinib when that gets approved based on the results of the QuANTUM-First trial, maybe even gilteritinib, when the gilteritinib comparison trials come out should be used with chemotherapy in the upfront setting and maintenance with FLT3 inhibitors is still an open question.