RT Journal Article
T1 The Mutational Landscape of Acute Myeloid Leukaemia Predicts Responses and Outcomes in Elderly Patients from the PETHEMA-FLUGAZA Phase 3 Clinical Trial.
A1 Ayala, Rosa
A1 Rapado, Inmaculada
A1 Onecha, Esther
A1 Martínez-Cuadrón, David
A1 Carreño-Tarragona, Gonzalo
A1 Bergua, Juan Miguel
A1 Vives, Susana
A1 Algarra, Jesus 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 López Lorenzo, Jose Luis
A1 Vidriales, María Belén
A1 Labrador, Jorge
A1 Falantes, José Francisco
A1 Sayas, María José
A1 Paiva, Bruno
A1 Barragán, Eva
A1 Prosper, Felipe
A1 Sanz, Miguel Ángel
A1 Martínez-López, Joaquín
A1 Montesinos, Pau
A1 On Behalf Of The Programa Para El Estudio de la Terapeutica En Hemopatias Malignas Pethema Cooperative Study Group, 
K1 NGS
K1 acute
K1 azacytidine
K1 clinical trials and observations
K1 complete remission
K1 cytarabine
K1 genetic risk
K1 leukemia
K1 leukemic cells
K1 myelocytic
K1 myeloid neoplasia
K1 older adults
K1 prognostic factors
K1 variants
AB We sought to predict treatment responses and outcomes in older patients with newly diagnosed acute myeloid leukemia (AML) from our FLUGAZA phase III clinical trial (PETHEMA group) based on mutational status, comparing azacytidine (AZA) with fludarabine plus low-dose cytarabine (FLUGA). Mutational profiling using a custom 43-gene next-generation sequencing panel revealed differences in profiles between older and younger patients, and several prognostic markers that were useful in young patients were ineffective in older patients. We examined the associations between variables and overall responses at the end of the third cycle. Patients with mutated DNMT3A or EZH2 were shown to benefit from azacytidine in the treatment-adjusted subgroup analysis. An analysis of the associations with tumor burden using variant allele frequency (VAF) quantification showed that a higher overall response was associated with an increase in TET2 VAF (odds ratio (OR), 1.014; p = 0.030) and lower TP53 VAF (OR, 0.981; p = 0.003). In the treatment-adjusted multivariate survival analyses, only the NRAS (hazard ratio (HR), 1.9, p = 0.005) and TP53 (HR, 2.6, p = 9.8 × 10-7) variants were associated with shorter overall survival (OS), whereas only mutated BCOR (HR, 3.6, p = 0.0003) was associated with a shorter relapse-free survival (RFS). Subgroup analyses of OS according to biological and genomic characteristics showed that patients with low-intermediate cytogenetic risk (HR, 1.51, p = 0.045) and mutated NRAS (HR, 3.66, p = 0.047) benefited from azacytidine therapy. In the subgroup analyses, patients with mutated TP53 (HR, 4.71, p = 0.009) showed a better RFS in the azacytidine arm. In conclusion, differential mutational profiling might anticipate the outcomes of first-line treatment choices (AZA or FLUGA) in older patients with AML. The study is registered at ClinicalTrials.gov as NCT02319135.
SN 2072-6694
YR 2021
FD 2021-05-18
LK http://hdl.handle.net/10668/17913
UL http://hdl.handle.net/10668/17913
LA en
DS RISalud
RD Apr 7, 2025