Comprehensive mutational profiling and clinical outcome of adults AML with NUP98 rearrangement
Abstract
Abstract Acute myeloid leukemia (AML) harboring NUP98 rearrangements (NUP98r) is recognized as a distinct entity in the 2022 WHO classification; however, it is not as a prognostic factor within the ELN 2022 classification. We report a large cohort of 95 adult patients with NUP98r AML. Patient characteristics included a young age (median 50 years [IQR 38-64]), 20% of therapy-related AML, a high WBC count (median 52×109/L), normal karyotype in 32%, FLT3-ITD in 48% and WT1 mutations in 34%. NUP98::NSD1 fusion was the most common (54%), and these patients were significantly younger (41y vs 61y), had more de novo AML (94% vs 64%), higher rates of normal karyotypes (56% vs 4.5%), FLT3-ITD (76% vs 18%) and WT1 mutations (50% vs 16%) than other NUP98r AML. The median overall survival (OS) for the entire cohort was 14.8 months (95% CI, 11.9–20.8) and event-free survival was 3.3 months (2-7.5). Among patients treated intensively (n=73), age (HR = 1.04) and FLT3 inhibitor therapy (HR = 0.45) influenced OS in univariate analysis, while leukocytosis, partner type, ELN classification, presence of a FLT3-ITD or WT1 mutation or hematopoietic stem cell transplant did not. Compared with NUP98 wild-type (WT) AML, NUP98r patients had a prognosis more similar to that of NUP98 WT ELN adverse patients whether initially classified as intermediate (20.3 months [11.7-30.2]) or adverse (15.7 months [13.5-42.9]). However, treatment with FLT3 inhibitors improved prognosis, with OS approaching that of intermediate-risk AML patients (33.3 months [11.9–not reached]).
Article Details
Authors (41)
Ducourneau Benoit
3CH VALENCIENNES, VALENCIENNES, France
Arnaud Pages
4Gustave Roussy Cancer Center, Department of Biostatistics and Epidemiology, villejuif, France
Stéphanie Struski
4Department of Hematology, University Hospital of Toulouse, Toulouse, France
Matthieu Decamp
5Department of Cytogenetic, University Hospital of Caen, Caen, France
Emmanuel Raffoux
Céline Berthon
29Service d’Hématologie, Centre Hospitalier Universitaire de Lille, Hôpital Claude-Huriez, Lille, France
Laurene Fenwarth
Unité Mixte de Recherche (UMR) 9020-UMR-S 1277-Canther-Cancer Heterogeneity, Plasticity and Resistance to Therapies, Institut de Recherche contre le Cancer de Lille, University of Lille, CNRS, Inserm, Centre Hospitalier Universitaire Lille, Lille, France
Vincent Marmouset
8Department of Hematology, Gustave Roussy, Université Paris-Saclay, Villejuif, France
Cécile Pautas
4Department of Hematology, Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris, Créteil, France
Thomas Cluzeau
15Service d’Hématologie, Centre Hospitalier Universitaire de Nice, Nice, France
Delphine Lebon
10CHU Amiens Picardie, Unité d'Hématologie clinique et Thérapie Cellulaire, Amiens, France
Madalina Uzunov
11Sorbonne Université, AP-HP, Pitié- Salpêtrière Hospital, Department of Clinical Haematology, Paris, France
Patricio Pereyra
11CABA – Alexander Fleming Institute, Olivos, Argentina
Maël Heiblig
9Department of Hematology, Centre Hospitalier Universitaire de Lyon, Lyon, France
Jean-Valère Malfuson
24Hôpital d'Instruction des Armées Percy, Clamart, Clamart, France
Laure Farnault
28Service d’Hématologie, Assistance Publique-Hôpitaux de Marseille–Hôpital de la Conception, Marseille, France
Pierre-Yves Dumas
Julia HIEULLE
2CH ROUBAIX, ROUBAIX, France
Sarah Bertoli
Sylvain Chantepie
10Department of Hematology, Centre Hospitalier Universitaire de Caen, Caen, France
Nathalie Auger
Department of Social and Preventive Medicine, School of Public Health, University of Montreal, QC, Canada (N.A.).
Audrey Bidet
21Laboratory of Hematology, Bordeaux University Hospital, Bordeaux, France
Marie Joelle Mozziconacci
22Laboratory of Hematology, Institut Paoli Calmettes, Marseille, France
Augustin Boudry
1Laboratory of Hematology, Centre Hospitalier Universitaire de Lille, Université de Lille, INSERM U1366, Lille, France
Isabelle Luquet
26Laboratory of Hematology, Centre Hospitalier Universitaire de Toulouse, Toulouse, France
Laureen Chat
1Leukemia Institute Paris Saint-Louis, Paris, France
Romain Loyaux
25Department of Biologie et pathologie médicales, Gustave Roussy, Université Paris-Saclay, Villejuif, France
Lina EL-MURR
8Department of Hematology, Gustave Roussy, Université Paris-Saclay, Villejuif, France
Emmanuelle Clappier
2Institut de Recherche Saint-Louis, Université Paris Cité, Paris, France
Claude Gardin
Hématologie Clinique, Hôpital Avicenne, AP-HP, Hôpitaux Universitaires Paris Seine Saint-Denis, Bobigny, France
Mathilde Hunault
2Department of Hematology, Centre Hospitalier Universitaire d’Angers, INSERM, Centre National de la Recherche Scientifique, Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes Angers, Fédération Hospitalo-Universitaire Grand Ouest Against Leukemia, Université d’Angers, Université de Nantes, Angers, France
Stéphane de Botton
Arnaud Pigneux
Dominique Penther
27Laboratory of Genetics, Centre Henri Becquerel, Rouen, France
Éric Delabesse
26Laboratory of Hematology, Centre Hospitalier Universitaire de Toulouse, Toulouse, France
Raphaël Itzykson
6Department of Hematology, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Paris, France
Claude Preudhomme
Unité Mixte de Recherche (UMR) 9020-UMR-S 1277-Canther-Cancer Heterogeneity, Plasticity and Resistance to Therapies, Institut de Recherche contre le Cancer de Lille, University of Lille, CNRS, Inserm, Centre Hospitalier Universitaire Lille, Lille, France
Hervé Dombret
Christian Récher
Nicolas Duployez
Unité Mixte de Recherche (UMR) 9020-UMR-S 1277-Canther-Cancer Heterogeneity, Plasticity and Resistance to Therapies, Institut de Recherche contre le Cancer de Lille, University of Lille, CNRS, Inserm, Centre Hospitalier Universitaire Lille, Lille, France
Jean-Baptiste Micol
28Gustave-Roussy, université Paris-Saclay, Department of Hematology, Villejuif, France