Cancers (Sep 2022)

Prognostic Relevance of <i>NPM1</i> and <i>FLT3</i> Mutations in Acute Myeloid Leukaemia, Longterm Follow-Up—A Single Center Experience

  • Erika Borlenghi,
  • Chiara Cattaneo,
  • Diego Bertoli,
  • Elisa Cerqui,
  • Silvana Archetti,
  • Angela Passi,
  • Margherita Oberti,
  • Tatiana Zollner,
  • Carlotta Giupponi,
  • Chiara Pagani,
  • Nicola Bianchetti,
  • Chiara Bottelli,
  • Samuele Bagnasco,
  • Margherita Sciumè,
  • Alessandra Tucci,
  • Giuseppe Rossi

DOI
https://doi.org/10.3390/cancers14194716
Journal volume & issue
Vol. 14, no. 19
p. 4716

Abstract

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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: 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.

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