The Impact of DNMT3A Status on NPM1 MRD Predictive Value and Survival in Elderly AML Patients Treated Intensively

Mael Heiblig (1) , Nicolas Duployez (2, 3) , Alice Marceau (2, 3) , Delphine Lebon (4, 5) , Laure Goursaud (6) , Isabelle Plantier (7) , Laure Stalnikiewich (8) , Nathalie Cambier (9) , Marie Balsat (1) , Gaelle Fossard (1) , Helene Labussiere (1) , Fiorenza Barraco (1) , Sophie Ducastelle (1) , Pierre Sujobert (1) , Sarah Huet (1) , Sandrine Hayette (1) , Herve Ghesquieres (1) , Xavier Thomas (1) , Claude Preudhomme (2, 3)

1 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]
2 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
3 CANTHER - Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277
4 CHU Amiens-Picardie
5 HEMATIM - HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666
6 CIIL - Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204
7 Centre Hospitalier de Roubaix
8 Service d'hématologie clinique [CH Lens]
9 Centre hospitalier [Valenciennes, Nord]

Simple Summary DNMT3A mutation has been associated with adverse outcomes. In this study, we aimed to investigate the impact of DNMT3A status on NPM1 MRD predictive value for survival in a retrospective cohort of acute myeloid leukemia (AML) patients aged over 60 years old treated intensively. A total of 138 patients treated for NPM1-mutated AML in two French institutions were analyzed retrospectively. A 4log reduction of NPM1 MRD was associated with a better outcome. DNMT3A negative patients who achieved a 4log reduction had a superior outcome to those who did not. However, postinduction NPM1 MRD1 reduction was not predictive of OS and LFS in DNMT3Amut patients. These results confirm that post-induction NPM1 MRD1 is a reliable tool to assess disease outcome in elderly AML patients. However, the presence of DNMT3A also identify a subgroup of patients at high risk of relapse. Minimal residual disease (MRD) is now a powerful surrogate marker to assess the response to chemotherapy in acute myeloid leukemia (AML). DNMT3A mutation has been associated with adverse outcomes. In this study, we aimed to investigate the impact of DNMT3A status on NPM1 MRD predictive value for survival in a retrospective cohort of AML patients aged over 60 years old treated intensively. A total of 138 patients treated for NPM1-mutated AML in two French institutions were analyzed retrospectively. DNMT3A status did not influence the probability of having a >= 4log MRD1 reduction after induction. Only 20.4% of FLT3-ITD patients reached >= 4log MRD1 reduction compared to 47.5% in FLT3wt cases. A 4log reduction of NPM1 MRD was associated with a better outcome, even in FLT3-ITD mutated patients, independent of the allelic ratio. DNMT3A negative patients who reached a 4log reduction had a superior outcome to those who did not (HR = 0.23; p < 0.001). However, postinduction NPM1 MRD1 reduction was not predictive of OS and LFS in DNMT3Amut patients. These results confirm that post-induction NPM1 MRD1 is a reliable tool to assess disease outcome in elderly AML patients. However, the presence of DNMT3A also identifies a subgroup of patients at high risk of relapse.

Mots clés: DNMT3A; NPM1; acute myeloid leukemia; elderly; prognosis

Domaines: Sciences du Vivant [q-bio]

Mael Heiblig, Nicolas Duployez, Alice Marceau, Delphine Lebon, Laure Goursaud, et al.. The Impact of DNMT3A Status on NPM1 MRD Predictive Value and Survival in Elderly AML Patients Treated Intensively. Cancers, 2021, 13 (9), ⟨10.3390/cancers13092156⟩. ⟨hal-03606391⟩