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

Antineoplastic Agents, Alkylating / therapeutic use Biomarkers, Tumor / genetics Chromosome Aberrations / drug effects Cytarabine / therapeutic use Cytogenetics / methods Female Humans Idarubicin / therapeutic use Karyotype Karyotyping / methods Leukemia, Myeloid, Acute / drug therapy Lomustine / therapeutic use Male Middle Aged Mutation / drug effects Nucleophosmin Prognosis

Journal

Leukemia

ISSN: 1476-5551

Titre abrégé: Leukemia

Pays: England

ID NLM: 8704895

Informations de publication

Date de publication:
05 2021

Historique:

received: 27 04 2020

accepted: 14 08 2020

revised: 23 07 2020

pubmed: 19 9 2020

medline: 16 6 2021

entrez: 18 9 2020

Statut: ppublish

Résumé

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-ITD

Identifiants

DOI: 10.1038/s41375-020-01031-1 PMID: 32943750

pubmed: 32943750

doi: 10.1038/s41375-020-01031-1

pii: 10.1038/s41375-020-01031-1

doi:

Substances chimiques

Antineoplastic Agents, Alkylating 0

Biomarkers, Tumor 0

NPM1 protein, human 0

Cytarabine 04079A1RDZ

Nucleophosmin 117896-08-9

Lomustine 7BRF0Z81KG

Idarubicin ZRP63D75JW

Banques de données

ClinicalTrials.gov

['NCT00590837']

Types de publication

Clinical Trial Journal Article Randomized Controlled Trial

Langues

eng

Sous-ensembles de citation

Pagination

1291-1300

Investigateurs

J-P Marolleau (JP)

A Aleme (A)

F Orsini-Piocelle (F)

N Cadoux (N)

N Ifrah (N)

M Hunault (M)

C Marie (C)

A Al Jijakli (A)

G Lepeu (G)

H Zerazhi (H)

M Beyrne (M)

A Banos (A)

S Labarrere (S)

E Deconinck (E)

M Peria (M)

A El Yamani (A)

O Kadiri (O)

B Choufi (B)

M Brument (M)

A Pigneux (A)

T Leguay (T)

P-Y Dumas (PY)

C Berthou (C)

G Guillerm (G)

G Drugmanne (G)

O Tournilhac (O)

G Roy (G)

B Audhuy (B)

S Camara (S)

D Caillot (D)

M Grandjean (M)

J-Y Cahn (JY)

C-E Bulabois (CE)

B Fief (B)

N Vey (N)

C Ladraa (C)

V Dorvaux (V)

M Hagopian (M)

N Fegueux (N)

C Fenoll (C)

V Sabadash (V)

M Ojeda (M)

C Haby (C)

F Witz (F)

C Bonmati (C)

M Lhuire (M)

J Delaunay (J)

P Peterlin (P)

L Airiau (L)

L Mannone (L)

I Touitou (I)

E Jourdan (E)

D Umuhire (D)

M Alexis (M)

O Michel (O)

F Dreyfus (F)

D Bouscary (D)

A Cheung (A)

L Sanhes (L)

F Touhami (F)

E Ribas (E)

M Puyade (M)

M-P Gallego-Hernanz (MP)

N Hugon (N)

C Himberlin (C)

L Maggi (L)

T Lamy (T)

A Testu (A)

E Tavernier (E)

S Marchand (S)

B Lioure (B)

C Kravanja (C)

L Benboubker (L)

D Nollet (D)

M Attal (M)

C Recher (C)

A Sarry (A)

A Lhermitte (A)

G Yrica (G)

D Schwartz (D)

N Le Montagner (N)

C Fenoll (C)

V Sabadash (V)

D Nollet (D)

L Auvray (L)

R Delepine (R)

A Fayault (A)

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