Fludarabine, high-dose cytarabine and idarubicin-based induction may overcome the negative prognostic impact of flt3-itd in npm1 mutated aml, irrespectively of flt3-itd allelic Burden

Paola Minetto, Anna Candoni, Fabio Guolo, Marino Clavio, Maria Elena Zannier, Maurizio Miglino, Maria Vittoria Dubbini, Enrico Carminati, Anna Sicuranza, Sara Ciofini, Nicoletta Colombo, Girolamo Pugliese, Riccardo Marcolin, Adele Santoni, Filippo Ballerini, Luca Lanino, Michele Cea, Marco Gobbi, Monica Bocchia, Renato FaninRoberto Massimo Lemoli

Research output: Contribution to journalArticlepeer-review

Abstract

The mutations of NPM1 and FLT3-ITD represent the most frequent genetic aberration in acute myeloid leukemia. Indeed, the presence of an NPM1 mutation reduces the negative prognostic impact of FLT3-ITD in patients treated with conventional “3+7” induction. However, little information is available on their prognostic role with intensified regimens. Here, we investigated the efficacy of a fludarabine, high-dose cytarabine and idarubicin induction (FLAI) in 149 consecutive fit AML patients (median age 52) carrying the NPM1 and/or FLT3-ITD mutation, treated from 2008 to 2018. One-hundred-and-twenty-nine patients achieved CR (86.6%). After a median follow up of 68 months, 3-year overall survival was 58.6%. Multivariate analysis disclosed that both NPM1mut (p < 0.05) and ELN 2017 risk score (p < 0.05) were significant predictors of survival. NPM1-mutated patients had a favorable outcome, with no significant differences between patients with or without concomitant FLT3-ITD (p = 0.372), irrespective of FLT3-ITD allelic burden. Moreover, in landmark analysis, performing allogeneic transplantation (HSCT) in first CR proved to be beneficial only in ELN 2017 high-risk patients. Our data indicate that FLAI exerts a strong anti-leukemic effect in younger AML patients with NPM1mut and question the role of HSCT in 1st CR in NPM1mut patients with concomitant FLT3-ITD.

Original languageEnglish
Article number34
Pages (from-to)1-13
Number of pages13
JournalCancers
Volume13
Issue number1
DOIs
Publication statusPublished - Jan 1 2021

Keywords

  • Acute myeloid leukemia
  • Allogeneic stem cell transplantation
  • FLT3-ITD
  • Intensified induction
  • Minimal residual disease assessment
  • NPM1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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