Impact of FLT3 Mutation on Outcomes after Venetoclax and Azacitidine for Patients with Treatment-Naive Acute Myeloid Leukemia

Purpose: To evaluate efficacy and safety of venetoclax + azacitidine among treatment-naive patients with FLT3-mutant acute myeloid Patients and Methods: Data were pooled from patients enrolled in a phase III study (NCT02993523) that compared patients treated with venetoclax + azacitidine or placebo + azacitidine and a prior phase Ib study (NCT02203773) where patients were treated with venetoclax + azacitidine. Enrolled patients were ineligible for intensive therapy due to age >_75 years and/or comorbidities. Patients on venetoclax + azacitidine received venetoclax 400 mg orally (days 1- 28) and azacitidine (75 mg/m2; days 1-7/28-day cycle). FLT3 mutation was analyzed centrally on pretreatment bone marrow aspirates.Results: In the biomarker evaluable population, FLT3 mutation was detected in 42 (15%) and 22 (19%) patients in the venetoclax + azacitidine and azacitidine groups. Composite complete remission [CRc; complete remission (CR) + CR with incomplete hematologic recovery (CRi)] rates (venetoclax + azacitidine/azacitidine) for FLT3-mutant patients were 67%/36%, median duration of remis-sion (DoR) was 17.3/5.0 months, and median OS was 12.5/ 8.6 months. The CRc rates among FLT3 wild-type patients were 67%/25%, median DoR 18.4/13.4 months, and median OS 14.7/ 10.1 months. In patients treated with venetoclax + azacitidine, CRc in patients with FLT3-ITD and FLT3-TKD was 63% and 77% and median OS was 9.9 and 19.2 months, and in comutated FLT3-ITD + NPM1 patients, CRc was 70%, median DoR was not reached, and median OS was 9.1 months. There were no unex-pected toxicities in the venetoclax + azacitidine group.Conclusions: When treated with venetoclax + azacitidine, patients with FLT3 mutations and FLT3 wild-type had similar outcomes. Future analyses in larger patient populations may further define the impact of venetoclax + azacitidine in patients harboring FLT3-ITD.