LSC17 score complements genetics and measurable residual disease in acute myeloid leukemia: an ALFA study

Loic Vasseur , Laurène Fenwarth (1) , Jérôme Lambert , Stéphane de Botton (2) , Martin Figeac (3) , Céline Villenet (3) , Maël Heiblig (4, 5, 6) , Pierre-Yves Dumas (7, 8) , Christian Récher (9) , Celine Berthon (10) , Emilie Lemasle (11) , Delphine Lebon (12, 13) , Juliette Lambert (14) , Christine Terré (15) , Karine Celli-Lebras (16) , Hervé Dombret (17) , Claude Preudhomme (18) , Meyling Cheok (19, 1) , Raphaël Itzykson (20) , Nicolas Duployez (21, 22)

1 CANTHER - Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277
2 Hôpital Edouard Herriot [CHU - HCL]
3 Plateforme de génomique fonctionnelle et structurelle [Lille]
4 UCBL - Université Claude Bernard Lyon 1
5 HCL - Hospices Civils de Lyon
6 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
7 CIML - Centre d'Immunologie de Marseille - Luminy
8 CHU Bordeaux [Bordeaux]
9 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
10 Hôpital Claude Huriez [Lille]
11 CLCC Henri Becquerel - Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen
12 CHU Amiens-Picardie
13 HEMATIM - HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666
14 UMR E007 - Thérapie génique et contrôle de l'expansion cellulaire
15 Département de Génétique [CH Versailles]
16 Service d'Hémato-oncologie [CHU Saint-Louis]
17 Hôpital Saint-Louis
18 Service d'Hématologie Cellulaire [Lille]
19 IRCL - Institut pour la recherche sur le cancer de Lille [Lille]
20 (EA_3518) - Recherche clinique appliquée à l'hématologie
21 Service de pathologie [CHU Lille]
22 CHRU Lille - Centre Hospitalier Régional Universitaire [Lille]

Whether the LSC17 gene expression can improve risk stratification in the context of NGS-based risk stratification and measurable residual disease (MRD) in AML patients treated intensively has not been explored. We analyzed LSC17 in 504 adult patients prospectively treated in the ALFA-0702 trial. Multiple (cyto)genetic alterations were associated with changes in LSC17, such as higher LSC17 in patients with RUNX1 or TP53 mutations, and lower scores in those with CEBPA and NPM1 mutations. LSC17-high patients had a lower rate of complete response (CR) or CR with incomplete platelet recovery (CRp) after one induction course in a multivariable analysis (OR=0.41, p=0.0007) accounting for European LeukemiaNet 2022 (ELN22) risk groups, age, and white blood cell (WBC) count. The LSC17-high status was associated with shorter overall survival (OS) (3-year OS: 70.0% versus 52.7% in LSC17-low patients, p<0.0001). In a multivariable analysis considering ELN22, age and WBC count, LSC17-high patients had shorter disease-free survival (DFS) (HR=1.36, p=0.048) compared to LSC17-low patients. In 123 NPM1-mutated patients in CR/CRp with available MRD data, LSC17-high status predicted poorer DFS (HR=2.34, p=0.01) independently of age, WBC count, ELN22 risk, and NPM1-MRD. Combining MRD and LSC17 status identified a subset of 48% of NPM1 patients with LSC17-low status and negative NPM1-MRD with a 3-year OS from CR/CRp of 93.1% compared to 60.7% in those with LSC17-high status and/or positive NPM1-MRD (p=0.0001). Overall, LSC17 assessment refines genetic risk stratification in adult AML patients treated intensively. Combined with MRD, LSC17 identifies a subset of NPM1-mutated AML patients with excellent clinical outcome.

Domaines: Sciences du Vivant [q-bio]

Loic Vasseur, Laurène Fenwarth, Jérôme Lambert, Stéphane de Botton, Martin Figeac, et al.. LSC17 score complements genetics and measurable residual disease in acute myeloid leukemia: an ALFA study. Blood Advances, 2023, ⟨10.1182/bloodadvances.2023010155⟩. ⟨hal-04106615⟩