ASH 2025 | Azacitidine, venetoclax, and gilteritinib in newly diagnosed FLT3-mutated AML: long-term follow-up

So the standard of care for older adults with FLT3-mutated AML is still azacitidine plus venetoclax. Obviously, we add a FLT3 inhibitor to younger patients with intensive chemotherapy, and there’s been some nice data about adding FLT3 inhibitors to azacitidine plus venetoclax, but some uncertainty about the long-term outcomes of these regimens. So in this abstract, we present long-term data of our Phase II study of azacitidine, venetoclax, and gilteritinib for older adults with FLT3-mutated AML. So we’ve treated 30 patients with this regimen, about three quarters of whom have FLT3 ITD mutations. We’ve already published, you know, very high response rates. So 96% CR, CRi rate, 90% CR rate, very high rates of MRD negativity, both by flow cytometry and, you know, next-generation sequencing MRD for FLT3 mutations. And so here at ASH, we’re presenting the long-term data. So, you know, in these 30 patients, we have a median survival now of almost 30 months, a three-year survival of 46%. And so just in contrast, if we compare that to historical data with azacitidine and venetoclax in FLT3-mutated disease, there’s a two-year survival of only about 20 to 40%. So we really feel that this is significantly improving outcomes for these patients. We saw benefits across all the different subgroups. It looks like maybe patients who have a baseline RAS pathway mutation may do a bit worse. And so I think this is still an unmet need. And so we talk a little about the safety of this regimen. I think that’s been one of the concerns about adopting this more widely outside of large academic practices. Two-thirds of the patients will need additional dose reductions of some of the medications, the azacitidine, venetoclax, or gilteritinib. But most patients are still receiving the planned doses in consolidation, five days of azacitidine, seven days of venetoclax, 28 days of gilteritinib. But it is a challenge to manage these patients, manage the myelosuppression. You do have to dose reduce quite frequently. We give growth factors. We give prophylaxis. But that being said, with optimal therapy, we really feel that this triplet regimen is an improvement over azacitidine and venetoclax. And there are randomized studies ongoing that are planning to evaluate this compared to standard intensive chemotherapy, even for younger patients with FLT3-mutated AML.

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