Background: The addition of multi-kinase inhibitors of FLT3 such as midostaurin and sorafenib to chemotherapy have demonstrated improved outcomes in patients with newly diagnosed FLT3 mutated AML Gilteritinib (gilt) is a second generation FLT3 inhibitor approved for pts with relapsed/refractory (R/R) FLT3-mutated AML. We studied to the combination of gilt with the CLIA regimen in FLT3 mutated AML. Methods: Eligible pts were between 18-65 years (yrs) with FLT3-mutated AML. Induction was: Cladribine 5 mg/m2 IV on D1-5, Cytarabine 1.5-2.0 g/m2 IV on D1-5, Idarubicin 10 mg/m2 IV on D1-3 and gilt 120 mg on D1-14. Consolidation was cladribine 5 mg/m2 IV for 3d, Cytarabine 750 mg/m2 IV for 3 d, and idarubicin 8 mg/m2 IV for 2 d, with gilt 120 mg continuously during cycle two onward. A historical cohort combining sorafenib (400 mg PO BID) with idarubicin + cytarabine (1.5 g/m2) backbone was used as comparison. Results: Twenty-four pts were enrolled with a median age of 53 yrs (range, 28-63). 21 pts (88%) had FLT3-ITD, 6 pts (25%) had FLT3-D835, and 3 pts (13%) had both. Nineteen pts (79%) had diploid cytogenetics, and 4 pts (18%) had trisomy 8. The most commonly co-occurring mutations were: NPM1 (46%), ASXL1 (29%), DNMT3A (29%), TET2 (25%), and KDM6A (20%). 16 pts (67%) achieved complete remission (CR), 2 (8%) had CR with incomplete recovery (CRi), for a CR/CRi rate of 75%. 13 responding pts (54%) underwent to allogeneic SCT. The median overall survival for the entire cohort was not reached. We compared these outcomes to our historical cohort of 107 pts treated with sorafenib combined with high-dose cytarabine-based chemotherapy. Other than older age and greater anemia for the gilt, there was not significant difference in baseline characteristics between the two groups. The CR/CRi rate was similar (75% gilt vs. 71% sorafenib; P = > 0.999) between the 2 cohorts; while there was a trend, there was no significant difference in OS with CLIA + Gilt (median NR vs. 17.3 months for sorafenib; P = 0.533). Conclusions: The combination of the FLT3 inhibitor gilteritinib to CLIA produced high rates of complete remission in pts diagnosed with FLT3-mutated AML. These results were similar for Sorafenib when combined with intensive chemotherapy with OS rates favoring gilteritinib. Further study of intensive chemotherapy with different FLT3 inhibitors is warranted. Clinical trial information: NCT02115295.