RT Journal Article
T1 Measurable residual disease in elderly acute myeloid leukemia: results from the PETHEMA-FLUGAZA phase 3 clinical trial.
A1 Simoes, Catia
A1 Paiva, Bruno
A1 Martinez-Cuadron, David
A1 Bergua, Juan-Miguel
A1 Vives, Susana
A1 Algarra, Lorenzo
A1 Tormo, Mar
A1 Martinez, Pilar
A1 Serrano, Josefina
A1 Herrera, Pilar
A1 Ramos, Fernando
A1 Salamero, Olga
A1 Lavilla, Esperanza
A1 Gil, Cristina
A1 Lopez, Jose-Luis
A1 Vidriales, Maria-Belen
A1 Labrador, Jorge
A1 Falantes, Jose-Francisco
A1 Sayas, María-Jose
A1 Ayala, Rosa
A1 Martinez-Lopez, Joaquin
A1 Villar, Sara
A1 Calasanz, Maria-Jose
A1 Prosper, Felipe
A1 San-Miguel, Jesus F
A1 Sanz, Miguel Angel
A1 Montesinos, Pau
AB The value of measurable residual disease (MRD) in elderly patients with acute myeloid leukemia (AML) is inconsistent between those treated with intensive vs hypomethylating drugs, and unknown after semi-intensive therapy. We investigated the role of MRD in refining complete remission (CR) and treatment duration in the phase 3 FLUGAZA clinical trial, which randomized 283 elderly AML patients to induction and consolidation with fludarabine plus cytarabine (FLUGA) vs 5-azacitidine. After consolidation, patients continued treatment if MRD was ≥0.01% or stopped if MRD was s ,0.01%, as assessed by multidimensional flow cytometry (MFC). On multivariate analysis including genetic risk and treatment arm, MRD status in patients achieving CR (N 5 72) was the only independent prognostic factor for relapse-free survival (RFS) (HR, 3.45; P 5 .002). Achieving undetectable MRD significantly improved RFS of patients with adverse genetics (HR, 0.32;P 5 .013). Longer overall survival was observed in patients with undetectable MRD after induction though not after consolidation. Although leukemic cells from most patients displayed phenotypic aberrancies vs their normal counterpart (N 5 259 of 265), CD34 progenitors from cases with undetectable MRD by MFC carried extensive genetic abnormalities identified by whole-exome sequencing. Interestingly, the number of genetic alterations significantly increased from diagnosis to MRD stages in patients treated with FLUGA vs 5-azacitidine (2.2-fold vs 1.1-fold; P 5 .001). This study supports MRD assessment to refine CR after semi-intensive therapy or hypomethylating agents, but unveils that improved sensitivity is warranted to individualize treatment and prolong survival of elderly AML patients achieving undetectable MRD.
PB American Society of Hematology
YR 2021
FD 2021
LK http://hdl.handle.net/10668/17127
UL http://hdl.handle.net/10668/17127
LA en
NO Simoes C, Paiva B, Martínez-Cuadrón D, Bergua JM, Vives S, Algarra L, et al. Measurable residual disease in elderly acute myeloid leukemia: results from the PETHEMA-FLUGAZA phase 3 clinical trial. Blood Adv. 2021 Feb 9;5(3):760-770
NO The authors acknowledge all investigators involved in the PETHEMAphase 3 FLUGAZA clinical trial. This work was supported by the CIBERONC (CB16/12/00369, CB16/12/00233, CB16/12/00489, and CB16/12/00284), Instituto de Salud Carlos III/Subdireccion General de InvestigaciónSanitaria Fondo de Investigacion en Salud (FIS no. PI16/01661 andPI16/00517), and the Plan de Investigacion de la Universidad de Navarra (PIUNA; 2014-18). This study was supported internationally by the Cancer Research UK, Fundacion Científica de la Asociacion Española Contra el Cáncer (FCAECC), and Fondazione AIRC per la Ricerca sul Cancro under the Accelerator Award Program (EDITOR [Early Detection and Intervention]).
DS RISalud
RD Apr 5, 2025