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Prognostic and therapeutic impacts of mutant TP53 variant allelic frequency in newly diagnosed acute myeloid leukemia.
Short, Nicholas J; Montalban-Bravo, Guillermo; Hwang, Hyunsoo; Ning, Jing; Franquiz, Miguel J; Kanagal-Shamanna, Rashmi; Patel, Keyur P; DiNardo, Courtney D; Ravandi, Farhad; Garcia-Manero, Guillermo; Takahashi, Koichi; Konopleva, Marina; Daver, Naval; Issa, Ghayas C; Andreeff, Michael; Kantarjian, Hagop; Kadia, Tapan M.
Afiliación
  • Short NJ; Department of Leukemia.
  • Montalban-Bravo G; Department of Leukemia.
  • Hwang H; Department of Biostatistics, and.
  • Ning J; Department of Biostatistics, and.
  • Franquiz MJ; Department of Leukemia.
  • Kanagal-Shamanna R; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Patel KP; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • DiNardo CD; Department of Leukemia.
  • Ravandi F; Department of Leukemia.
  • Garcia-Manero G; Department of Leukemia.
  • Takahashi K; Department of Leukemia.
  • Konopleva M; Department of Leukemia.
  • Daver N; Department of Leukemia.
  • Issa GC; Department of Leukemia.
  • Andreeff M; Department of Leukemia.
  • Kantarjian H; Department of Leukemia.
  • Kadia TM; Department of Leukemia.
Blood Adv ; 4(22): 5681-5689, 2020 11 24.
Article en En | MEDLINE | ID: mdl-33211826
ABSTRACT
TP53 mutations are associated with poor outcomes in acute myeloid leukemia (AML). The prognostic impact of mutant TP53 (TP53mut) variant allelic frequency (VAF) is not well established, nor is how this information might guide optimal frontline therapy. We retrospectively analyzed 202 patients with newly diagnosed TP53-mutated AML who underwent first-line therapy with either a cytarabine- or hypomethylating agent (HMA)-based regimen. By multivariate analysis, TP53mut VAF >40% was independently associated with a significantly higher cumulative incidence of relapse (P = .003) and worse relapse-free survival (P = .001) and overall survival (OS; P = .003). The impact of TP53mut VAF on clinical outcomes was driven by patients treated with a cytarabine-based regimen (median OS, 4.7 vs 7.3 months for VAF >40% vs ≤40%; P = .006), whereas VAF did not significantly affect OS in patients treated with HMA. The addition of venetoclax to HMA did not significantly affect OS compared with HMA without venetoclax, both in the entire TP53-mutated population and in patients stratified by TP53mut VAF. Among patients with TP53mut VAF ≤40%, OS was superior in those treated with higher-dose cytarabine, whereas OS was similarly poor for patients with TP53mut VAF >40% regardless of therapy. The best long-term outcomes were observed in those with 1 TP53 mutation with VAF ≤40% who received a frontline cytarabine-based regimen (2-year OS, 38% vs 6% for all others; P < .001). In summary, TP53mut VAF provides important prognostic information that may be considered when selecting frontline therapy for patients with newly diagnosed TP53-mutated AML.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Mieloide Aguda / Proteína p53 Supresora de Tumor Tipo de estudio: Diagnostic_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Blood Adv Año: 2020 Tipo del documento: Article Pais de publicación: EEUU / ESTADOS UNIDOS / ESTADOS UNIDOS DA AMERICA / EUA / UNITED STATES / UNITED STATES OF AMERICA / US / USA

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Mieloide Aguda / Proteína p53 Supresora de Tumor Tipo de estudio: Diagnostic_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Blood Adv Año: 2020 Tipo del documento: Article Pais de publicación: EEUU / ESTADOS UNIDOS / ESTADOS UNIDOS DA AMERICA / EUA / UNITED STATES / UNITED STATES OF AMERICA / US / USA