| Summary: | The prognosis of acute myeloid leukemia depends on genetic aberrations, particularly <i>NPM1</i> and <i>FLT3</i>-ITD mutations. The targeted drugs’ availability has renewed interest in <i>FLT3</i> 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 <i>FLT3</i> (ITD or TKD) and/or <i>NPM1</i> mutations. The CR rate and 5-y survival were 88.3% and 58% +/− 4, respectively, significantly higher in the <i>NPM1</i>-mutated (CR 93.9%, <i>p</i>: 0.0001; survival 71% +/− 6, <i>p</i>: 0.0017, respectively). In isolated ITD patients, the CR was lower (66.7%, <i>p</i>: 0.0009), and the 3 years-relapse-free survival worse (24%, <i>p</i>: <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 <i>NPM1</i>-co-mutated patients. Our data indicate that a high dose of ARAC plus idarubicin consolidation exerts a strong anti-leukemic effect in <i>NPM1</i>-mutated patients both with the <i>FLT3</i> wild-type and mutated AML, while in the <i>NPM1</i> wild-type and <i>FLT3</i>-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.
|
|---|