%0 Journal Article
%A Simoes, Catia
%A Paiva, Bruno
%A Martinez-Cuadron, David
%A Bergua, Juan-Miguel
%A Vives, Susana
%A Algarra, Lorenzo
%A Tormo, Mar
%A Martinez, Pilar
%A Serrano, Josefina
%A Herrera, Pilar
%A Ramos, Fernando
%A Salamero, Olga
%A Lavilla, Esperanza
%A Gil, Cristina
%A Lopez, Jose-Luis
%A Vidriales, Maria-Belen
%A Labrador, Jorge
%A Falantes, Jose-Francisco
%A Sayas, María-Jose
%A Ayala, Rosa
%A Martinez-Lopez, Joaquin
%A Villar, Sara
%A Calasanz, Maria-Jose
%A Prosper, Felipe
%A San-Miguel, Jesus F
%A Sanz, Miguel Angel
%A Montesinos, Pau
%T Measurable residual disease in elderly acute myeloid leukemia: results from the PETHEMA-FLUGAZA phase 3 clinical trial.
%D 2021
%U http://hdl.handle.net/10668/17127
%X 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.
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