Measurable residual disease in elderly acute myeloid leukemia: results from the PETHEMA-FLUGAZA phase 3 clinical trial
Por:
Simoes, C, Paiva, B, Martinez-Cuadron, D, Bergua, J, Vives, S, Algarra, L, Tormo, M, Martinez, P, Serrano, J, Herrera, P, Ramos, F, Salamero, O, Lavilla, E, Gil, C, Lopez, J, Vidriales, M, Labrador, J, Falantes, J, Sayas, M, Ayala, R, Martinez-Lopez, J, Villar, S, Calasanz, M, Prosper, F, San-Miguel, J, Sanz, M, Montesinos, P and Programa Estudio Terapeutica Hemop
Publicada:
9 feb 2021
Resumen:
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 <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 - 72) was the only independent prognostic factor for relapse-free survival (RFS) (HR, 3.45; P = .002). Achieving undetectable MRD significantly improved RFS of patients with adverse genetics (HR, 0.32; P = .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 = 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 = .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.
Filiaciones:
Simoes, C:
Clin Univ Navarra, Dept Hematol, Pamplona, Spain
Ctr Invest Med Aplicada CIMA, Pamplona, Spain
Inst Invest Sanitaria Navarra IDISNA, Pamplona, Spain
Paiva, B:
Clin Univ Navarra, Dept Hematol, Pamplona, Spain
Ctr Invest Med Aplicada CIMA, Pamplona, Spain
Inst Invest Sanitaria Navarra IDISNA, Pamplona, Spain
Martinez-Cuadron, D:
Hosp Univ & Politecn La Fe, Valencia, Spain
Bergua, J:
Hosp San Pedro de Alcantara, Caceres, Spain
Vives, S:
Hosp Badalona Germans Trias & Pujol, Inst Catalan Oncol ICO, Badalona, Spain
Algarra, L:
Hosp Gen Albacete, Albacete, Spain
Tormo, M:
Hosp Clin Univ Valencia, Valencia, Spain
Martinez, P:
Hosp Univ 12 Octubre, Madrid, Spain
Serrano, J:
Hosp Reina Sofia, Cordoba, Spain
Inst Maimonides Invest Biomed Cordoba IMIBIC, Cordoba, Spain
Herrera, P:
Hosp Univ Ramon y Cajal, Madrid, Spain
Ramos, F:
Hosp Univ Leon, Leon, Spain
Salamero, O:
Hosp Univ Vall dHebron, Barcelona, Spain
Lavilla, E:
Hosp Lucus Augusti, Lugo, Spain
:
Hosp Gen Univ Alicante, Alicante, Spain
Lopez, J:
Fdn Jimenez Diaz, Madrid, Spain
Vidriales, M:
Hosp Clin Univ Salamanca, Salamanca, Spain
Labrador, J:
Hosp Univ Burgos, Burgos, Spain
Falantes, J:
Complejo Hosp Virgen del Rocio, Seville, Spain
Sayas, M:
Univ Hosp Dr Peset, Valencia, Spain
Ayala, R:
Hosp Univ 12 Octubre, Madrid, Spain
Martinez-Lopez, J:
Hosp Univ 12 Octubre, Inst Invest Octubre 12, Madrid, Spain
Univ Complutense, Madrid, Spain
Ctr Nacl Invest Oncol CNIO, Madrid, Spain
Villar, S:
Clin Univ Navarra, Dept Hematol, Pamplona, Spain
Ctr Invest Med Aplicada CIMA, Pamplona, Spain
Calasanz, M:
Ctr Invest Med Aplicada CIMA, Pamplona, Spain
Univ Navarra, Dept Biochem, Navarra, Spain
Prosper, F:
Clin Univ Navarra, Dept Hematol, Pamplona, Spain
Ctr Invest Med Aplicada CIMA, Pamplona, Spain
San-Miguel, J:
Clin Univ Navarra, Dept Hematol, Pamplona, Spain
Ctr Invest Med Aplicada CIMA, Pamplona, Spain
Inst Invest Sanitaria Navarra IDISNA, Pamplona, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Canc CIBER ONC, Area Oncol, Madrid, Spain
Sanz, M:
Hosp Univ & Politecn La Fe, Valencia, Spain
Montesinos, P:
Hosp Univ & Politecn La Fe, Valencia, Spain
Green Published, gold
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