...To determine the MRD response of patients with FLT3-mutated AML in the MRD failure stratum to their first exposure to decision rule guided therapy with Venetoclax and Gilteritinib. ...

Eighteen patients were treated with Gilt-Ven based therapies for FLT-3 mutated R/R AML...Overall Response Rate (CR+CRi+MLFS) was 83%; Complete remission rate was 50%...In a real-world setting, Gilt-Ven based therapy is effective for heavily pre-treated patients with FLT-3 mutated R/R AML, especially as a bridge to AlloHSCT.

Nine patients achieved CR, 2 patients achieved CRh and 1 patient achieved complete remission with incomplete hematologic recovery (CRi). The CRc rate (CR/CRh) was 61.1% (11/18, 95% CI: 38.6%-83.6%)….Triplet therapy of GILT+DEC+VEN inND FLT3m AML patients ≥60 years old induced a high response rate (CRc rate 61.1%)...

The overall response rate (ORR) was 87% with 4 (50%) pts achieving CR/CRi (1 CR, 3 CRi) and 3 (37%) pts achieving MLFS. One pt withdrew from the study in cycle 1 and was not evaluable for response. The ORR in pts with prior HMA+VEN was 83% (3 CRi, 2 MLFS). Five of 7 responders (71%) achieved the best response within 1 cycle and 2 (29%) within 2 cycles. Pts received a median of 2 cycles of therapy (range, 1-6)...The combination therapy with ASTX727, VEN, and gilteritinib appears to be effective and safe in R/R FLT3 mutated AML and HR-MDS.

In this phase I/II study, pts with either R/R FLT3­-mutated AML or ND FLT3-mutated AML who were unsuitable for intensive chemotherapy were eligible….The combination of azacitidine, venetoclax and gilteritinib is effective in pts with FLT3-mutated AML.

The mCRc rate for FLT3mut patients was 75% (CR, 18%; CR with incomplete blood count recovery, 4%; CR with incomplete platelet recovery, 18%; and morphologic leukemia-free state, 36%) and was similar among patients with or without prior FLT3 inhibitor therapy (80% v 67%, respectively).... FLT3 molecular response (< 10-2) was achieved in 60% of evaluable mCRc patients (n = 15 of 25). The median overall survival for FLT3mut patients was 10.0 months....The combination of venetoclax and gilteritinib was associated with high mCRc and FLT3 molecular response rates...

...this multicenter, open-label, phase 1b trial (NCT03625505) to evaluate Ven + Gilt for R/R AML. Here, we report final response and survival endpoints, and molecular clearance among patients (pts) treated at the recommended phase two dose (RP2D)....Pts in the dose expansion cohort received Ven 400 mg + Gilt 120 mg (RP2D) daily in 28-day cycles, following Ven ramp-up....Ven + Gilt achieved high mCRc in patients with R/R FLT3+ AML, with or without prior TKI exposure, and an encouraging mOS. 

In this phase I/II study, pts with either R/R FLT3­-mutated AML or high-risk MDS/CMML or pts with ND FLT3-mutated AML who were unsuitable for intensive chemotherapy were eligible….The overall response rate (CR+CRi+MLFS) was 67%. One pt (7%) achieved CR as best response, 3 (20%) achieved CRi, and 6 (40%) achieved MLFS....With a median follow-up of 9.9 months in the R/R cohort, the median duration of response was 9.0 months and the median OS was 10.5 months...The combination of azacitidine, venetoclax and gilteritinib was effective in pts with FLT3-mutated AML. Gilteritinib dosing at 80mg daily was associated with a better safety/efficacy profile...

...mCRc was achieved by 86% of FLT3Mut+ efficacy population (36/42) with median time to first response of 1.0 mo (range: 0.7–4.6) and 86% with prior FLT3 tyrosine kinase inhibitor (TKI) exposure (24/28)....Ven+Gilt achieved high rates of mCRc in patients with heavily pretreated and prior TKI-exposed R/R FLT3Mut+ AML...

...DEC10-VEN + FLT3i is safe and effective for previously treated FLT3mut AML, and an excellent frontline option for older pts with treatment-naïve AML.