Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2025 Apr 1;131(7):e35824.
doi: 10.1002/cncr.35824.

Upfront intensive treatment analysis of the Italian Cohort Study on FLT3-mutated AML patients (FLAM): The impact of a FLT3 inhibitor addition to standard chemotherapy in the real-life setting

Jacopo Nanni  1 , Irene Azzali  2 , Cristina Papayannidis  3 , Antonino Mulè  4 , Ernesta Audisio  5 , Maria Paola Martelli  6 , Barbara Scappini  7 , Patrizia Chiusolo  8 , Benedetta Cambò  9 , Anna Candoni  10 , Monia Lunghi  11 , Francesco Albano  12 , Attilio Olivieri  13 , Nicola Fracchiolla  14 , Massimo Bernardi  15 , Claudio Romani  16 , Gian Matteo Rigolin  17 , Maria Benedetta Giannini  2 , Monica Bocchia  18 , Elisabetta Todisco  19   20 , Daniela Cilloni  21 , Maria Teresa Bochicchio  2 , Emanuela Ottaviani  1   3 , Agnese Mattei  2 , Federica Zamagni  2 , Irene Valli  2 , Roberta Volpi  2 , Giovanni Marconi  2 , Elisabetta Petracci  2 ; FLAM Collaborative Group; Giovanni Martinelli  2
Collaborators, Affiliations
Observational Study

Upfront intensive treatment analysis of the Italian Cohort Study on FLT3-mutated AML patients (FLAM): The impact of a FLT3 inhibitor addition to standard chemotherapy in the real-life setting

Jacopo Nanni et al. Cancer. .

Abstract

Background: The addition of a FLT3 inhibitor (FLT3i) to standard chemotherapy to treat fit newly diagnosed (ND) patients with FLT3-mutated acute myeloid leukemia (AML) represents the standard of care resulting from clinical trial results. However, evidence regarding FLT3i adoption in routine clinical practice is still scarce.

Methods: Clinical data are reported from 394 ND patients with FLT3-mutated AML enrolled in the retrospective observational Italian Cohort Study on FLT3-mutated patients with AML and treated with an upfront intensive regimen with (FLT3i group, n = 92) or without (CT group, n = 302) the addition of a FLT3i.

Results: With a median follow-up time of 34.5 months, an effectiveness benefit obtained by FLT3i incorporation both in terms of overall survival (median, 34.9 in the FLT3i vs 12.7 months in the CT group, p < .01) and relapse-free survival (median, 18.9 in the FLT3i vs 7.6 months in the CT group, p = .01) was documented, with a higher composite complete remission rate (75.4% in the FLT3i vs 62.4% in the CT group, p = .052). FLT3i benefit seemed to be independent from the transplant rate.

Conclusions: In conclusion, the benefit of FLT3i addition to upfront intensive treatment in newly diagnosed FLT3-mutated AML patients was confirmed in a large, real-life cohort study.

Keywords: FLT3 gene mutation; FLT3 inhibitor; acute myeloid leukemia; intensive treatment; real‐life setting; standard chemotherapy.

PubMed Disclaimer

Conflict of interest statement

GM: Consultant/speaker bureau of Abbvie, Astellas, AstraZeneca, Immunogen, Jansenn, Menarini/Stemline, Pfizer, Ryvu, Servier, Syros, and Takeda; research support from Abbvie, Astellas, AstraZeneca, Daiichi Sankyo, Pfizer, and Syros. CP: Honoraria of Astellas and Novartis, Advisory Board of Astellas and Novartis. All other authors have no conflicts of interest to disclose.

Figures

FIGURE 1
FIGURE 1
Consort diagram: Overall FLAM study population and patient selection for this analysis on patients with newly diagnosed FLT3‐mutated AML treated intensively. FLAM indicates Italian Cohort Study on FLT3‐mutated AML patients.
FIGURE 2
FIGURE 2
Kaplan–Meier estimates of relapse‐free survival for patients receiving an FLT3 inhibitor in addition to a standard chemotherapy program and for patients receiving standard chemotherapy alone.
FIGURE 3
FIGURE 3
Aalen–Johansen estimate of (a) cumulative incidence of relapse (CIR) between the different treatment groups and (b) cumulative incidence of death (CID) after the achievement of complete remission between the different treatment groups.
FIGURE 4
FIGURE 4
Kaplan–Meier estimates of survival for patients receiving an FLT3 inhibitor in addition to a standard chemotherapy program and for patients receiving standard chemotherapy alone.
FIGURE 5
FIGURE 5
Kaplan–Meier estimates of event‐free survival for patients receiving an FLT3 inhibitor in addition to a standard chemotherapy program and for patients receiving standard chemotherapy alone.
See this image and copyright information in PMC

References

    1. Döhner H, Weisdorf DJ, Bloomfield CD. Acute myeloid leukemia. N Engl J Med. 2015;373(12):1136‐1152. doi:10.1056/NEJMra1406184 - DOI - PubMed
    1. Papaemmanuil E, Gerstung M, Bullinger L, et al. Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med. 2016;374(23):2209‐2221. doi:10.1056/NEJMoa1516192 - DOI - PMC - PubMed
    1. Tazi Y, Arango‐Ossa JE, Zhou Y, et al. Unified classification and risk‐stratification in acute myeloid leukemia. medRxiv. January 2022. 2022.03.09.22271087. doi:10.1101/2022.03.09.22271087 - DOI - PMC - PubMed
    1. Döhner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129(4):424‐447. doi:10.1182/blood-2016-08-733196 - DOI - PMC - PubMed
    1. Döhner H, Wei AH, Appelbaum FR, et al. Diagnosis and management of AML in adults: 2022 ELN recommendations from an international expert panel. Blood. 2022:blood.2022016867. doi:10.1182/blood.2022016867 - DOI - PubMed

Publication types

MeSH terms

Substances