Lomustine is beneficial to older AML with ELN2017 adverse risk profile and intermediate karyotype: a FILO study - Aix-Marseille Université Access content directly
Journal Articles Leukemia Year : 2021

Lomustine is beneficial to older AML with ELN2017 adverse risk profile and intermediate karyotype: a FILO study

Laetitia Largeaud (1, 2) , Pascale Cornillet-Lefebvre (3) , Jean-François Hamel (4, 5) , Pierre-Yves Dumas (6, 7) , Naïs Prade (1, 2) , Stéphanie Dufrechou (1, 2) , Julien Plenecassagnes (8) , Isabelle Luquet (9) , Odile Blanchet , Anne Banos (10) , Marie Béné (11) , Marc Bernard (12) , Sarah Bertoli (9) , Caroline Bonmati (13) , Luc Matthieu Fornecker (14) , Romain Guièze (15) , Lamya Haddaoui (16) , Mathilde Hunault (5) , Jean Christophe Ianotto (17) , Eric Jourdan (18, 19) , Mario Ojeda , Pierre Peterlin , Norbert Vey (20, 21) , Hacene Zerazhi , Hicheri Yosr , Ariane Mineur , Jean-Yves Cahn , Norbert Ifrah , Christian Récher , Arnaud Pigneux , Eric Delabesse , J.-P. Marolleau , A. Aleme , F. Orsini-Piocelle , N. Cadoux , Norbert Ifrah , Mathilde Hunault , C. Marie , A. Al Jijakli , G. Lepeu , Hacene Zerazhi , M. Beyrne , Anne Banos , S. Labarrere , E. Deconinck , M. Peria , A. El Yamani , O. Kadiri , B. Choufi , M. Brument , Arnaud Pigneux , T. Leguay , Pierre-Yves Dumas , C. Berthou , G. Guillerm , G. Drugmanne , O. Tournilhac , G. Roy , B. Audhuy , S. Camara , D. Caillot , M. Grandjean , Jean-Yves Cahn , C.-E. Bulabois , B. Fief , Norbert Vey (20, 21) , C. Ladraa , V. Dorvaux , M. Hagopian , N. Fegueux , C. Fenoll , V. Sabadash , Mario Ojeda , C. Haby , F. Witz , Caroline Bonmati , M. Lhuire , J. Delaunay , Pierre Peterlin , L. Airiau , L. Mannone , I. Touitou , Eric Jourdan , D. Umuhire , M. Alexis , O. Michel , F. Dreyfus , D. Bouscary , A. Cheung , L. Sanhes , F. Touhami , E. Ribas , M. Puyade , M.-P. Gallego-Hernanz , N. Hugon , C. Himberlin , L. Maggi , T. Lamy , A. Testu , E. Tavernier , S. Marchand , B. Lioure , C. Kravanja , L. Benboubker , D. Nollet , M. Attal , Christian Récher , A. Sarry , A. Lhermitte , G. Yrica , D. Schwartz , N. Le Montagner , C. Fenoll , V. Sabadash , D. Nollet , L. Auvray , R. Delepine , A. Fayault
Odile Blanchet
  • Function : Author
Lamya Haddaoui
  • Function : Author
Mario Ojeda
  • Function : Author
Pierre Peterlin
Hacene Zerazhi
  • Function : Author
Hicheri Yosr
  • Function : Author
Ariane Mineur
  • Function : Author
Jean-Yves Cahn
  • Function : Author
Norbert Ifrah
  • Function : Author
Christian Récher
Arnaud Pigneux
  • Function : Author
Eric Delabesse
J.-P. Marolleau
  • Function : Author
  • PersonId : 887235
  • IdRef : 06981676X
A. Aleme
  • Function : Author
F. Orsini-Piocelle
  • Function : Author
N. Cadoux
  • Function : Author
Norbert Ifrah
  • Function : Author
Mathilde Hunault
  • Function : Author
C. Marie
  • Function : Author
A. Al Jijakli
  • Function : Author
G. Lepeu
  • Function : Author
Hacene Zerazhi
  • Function : Author
M. Beyrne
  • Function : Author
Anne Banos
  • Function : Author
S. Labarrere
  • Function : Author
E. Deconinck
  • Function : Author
M. Peria
  • Function : Author
A. El Yamani
  • Function : Author
O. Kadiri
  • Function : Author
B. Choufi
  • Function : Author
M. Brument
  • Function : Author
Arnaud Pigneux
  • Function : Author
T. Leguay
  • Function : Author
Pierre-Yves Dumas
C. Berthou
  • Function : Author
G. Guillerm
  • Function : Author
G. Drugmanne
  • Function : Author
O. Tournilhac
  • Function : Author
G. Roy
  • Function : Author
B. Audhuy
  • Function : Author
S. Camara
  • Function : Author
D. Caillot
  • Function : Author
M. Grandjean
  • Function : Author
Jean-Yves Cahn
  • Function : Author
C.-E. Bulabois
  • Function : Author
B. Fief
  • Function : Author
C. Ladraa
  • Function : Author
V. Dorvaux
  • Function : Author
M. Hagopian
  • Function : Author
N. Fegueux
  • Function : Author
C. Fenoll
  • Function : Author
V. Sabadash
  • Function : Author
Mario Ojeda
  • Function : Author
C. Haby
  • Function : Author
F. Witz
  • Function : Author
Caroline Bonmati
  • Function : Author
M. Lhuire
  • Function : Author
J. Delaunay
  • Function : Author
Pierre Peterlin
L. Airiau
  • Function : Author
L. Mannone
  • Function : Author
I. Touitou
  • Function : Author
Eric Jourdan
  • Function : Author
D. Umuhire
  • Function : Author
M. Alexis
  • Function : Author
O. Michel
  • Function : Author
F. Dreyfus
  • Function : Author
D. Bouscary
  • Function : Author
A. Cheung
  • Function : Author
L. Sanhes
  • Function : Author
F. Touhami
  • Function : Author
E. Ribas
  • Function : Author
M. Puyade
  • Function : Author
M.-P. Gallego-Hernanz
  • Function : Author
N. Hugon
  • Function : Author
C. Himberlin
  • Function : Author
L. Maggi
  • Function : Author
T. Lamy
  • Function : Author
A. Testu
  • Function : Author
E. Tavernier
  • Function : Author
S. Marchand
B. Lioure
  • Function : Author
C. Kravanja
  • Function : Author
L. Benboubker
  • Function : Author
D. Nollet
  • Function : Author
M. Attal
  • Function : Author
  • PersonId : 944589
Christian Récher
A. Sarry
  • Function : Author
A. Lhermitte
  • Function : Author
G. Yrica
  • Function : Author
D. Schwartz
  • Function : Author
N. Le Montagner
  • Function : Author
C. Fenoll
  • Function : Author
V. Sabadash
  • Function : Author
D. Nollet
  • Function : Author
L. Auvray
  • Function : Author
R. Delepine
  • Function : Author
A. Fayault
  • Function : Author

Abstract

We previously reported the benefit of lomustine addition to conventional chemotherapy in older acute myeloid leukemias with nonadverse chromosomal aberrations in the LAM-SA 2007 randomized clinical trial (NCT00590837). A molecular analysis of 52 genes performed in 330 patients included in this trial, 163 patients being treated with lomustine in combination with idarubicin and cytarabine and 167 without lomustine, identified 1088 mutations with an average of 3.3 mutations per patient. NPM1, FLT3, and DNMT3A were the most frequently mutated genes. A putative therapeutic target was identified in 178 patients (54%). Among five molecular classifications analyzed, the ELN2017 risk classification has the stronger association with the clinical evolution. Patients not treated with lomustine have an expected survival prognosis in agreement with this classification regarding the overall and event-free survivals. In strong contrast, lomustine erased the ELN2017 classification prognosis. The benefit of lomustine in nonadverse chromosomal aberrations was restricted to patients with RUNX1, ASXL1, TP53, and FLT3-ITDhigh/NPM1WT mutations in contrast to the intermediate and favorable ELN2017 patients. This post-hoc analysis identified a subgroup of fit elderly AML patients with intermediate cytogenetics and molecular markers who may benefit from lomustine addition to intensive chemotherapy.

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Cancer
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hal-03623649 , version 1 (24-03-2023)

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Attribution - NonCommercial

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Laetitia Largeaud, Pascale Cornillet-Lefebvre, Jean-François Hamel, Pierre-Yves Dumas, Naïs Prade, et al.. Lomustine is beneficial to older AML with ELN2017 adverse risk profile and intermediate karyotype: a FILO study. Leukemia, 2021, 35 (5), pp.1291-1300. ⟨10.1038/s41375-020-01031-1⟩. ⟨hal-03623649⟩
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