LAUSR

Simple Summary In acute myeloid leukemia, molecular genetics abnormalities, particularly NPM1 and FLT3 mutations, have a recognized prognostic role in the ELN risk classification and guide treatment decisions, especially since the availability of FLT3-targeted drugs. The NILG-AML 01/00 protocol uses a modified induction approach (ICE) and delivers the most active cytostatic agents at maximal doses in consolidation (a high dose of ARAC plus idarubicin) with autologous stem cell support. It calls for allogeneic transplant only in ELN high-risk patients including NPM1-wt FLT3-ITD-mutated patients. The results obtained from 171 patients showed that the median survival was not reached, and 5y-OS was 58% +/− 4. The prognostic influence of co-mutated FLT3 was overcome, and the efficacy of this treatment reduced the need for early consolidation with an allogeneic transplant in double-mutated patients, in their first complete remission. These data could represent the benchmark against which results of therapeutic programs using second-generation FLT3-targeted drugs should be compared. Abstract The prognosis of acute myeloid leukemia depends on genetic aberrations, particularly NPM1 and FLT3-ITD mutations. The targeted drugs’ availability has renewed interest in FLT3 mutations, but the impact of these genetic alterations using these treatments is yet to be confirmed. Our objective was to evaluate the results obtained with the intensified NILG-AML 01/00 protocol (ClinicalTrials.gov Identifier: NCT 00400673) in 171 unselected patients (median age, 54.5 years, range 15–74) carrying the FLT3 (ITD or TKD) and/or NPM1 mutations. The CR rate and 5-y survival were 88.3% and 58% +/− 4, respectively, significantly higher in the NPM1-mutated (CR 93.9%, p: 0.0001; survival 71% +/− 6, p: 0.0017, respectively). In isolated ITD patients, the CR was lower (66.7%, p: 0.0009), and the 3 years-relapse-free survival worse (24%, p: <0.0002). The presence of ITD, irrespective of the allelic ratio, or TKD mutation, did not significantly affect the survival or relapse-free survival among the NPM1-co-mutated patients. Our data indicate that a high dose of ARAC plus idarubicin consolidation exerts a strong anti-leukemic effect in NPM1-mutated patients both with the FLT3 wild-type and mutated AML, while in the NPM1 wild-type and FLT3-mutated, the therapeutic effect remains unsatisfactory. New strategies incorporating target therapy with second-generation inhibitors will improve these results and their addition to this aggressive chemotherapeutic program merits testing.