Impact of TP53 Mutation Status in Elderly AML Patients When Adding All-Trans Retinoic Acid or Valproic Acid to Decitabine

Helena Bresser, Claudia Schmoor, Olga Grishina, Dietmar Pfeifer, Johanna Thomas, Usama Ur Rehman, Martina Crysandt, Edgar Jost, Felicitas Thol, Michael Heuser, Katharina S Götze, Richard F Schlenk, Helmut R Salih, Marcus M Schittenhelm, Gerhard Heil, Carsten Schwaenen, Carsten Müller-Tidow, Wolfram Brugger, Andrea Kündgen, Maike de WitAristoteles Giagounidis, Sebastian Scholl, Andreas Neubauer, Jürgen Krauter, Gesine Bug, Annette M May, Ralph Wäsch, Justus Duyster, Konstanze Döhner, Arnold Ganser, Hartmut Döhner, Björn Hackanson, Heiko Becker, Michael Lübbert

Publikation: Beitrag in FachzeitschriftArtikelBegutachtung

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Abstract

In a randomized phase II trial (AMLSG 14-09, NCT00867672) of elderly, newly diagnosed AML patients, ATRA combined with decitabine (DEC) significantly improved the overall response rate (ORR) and survival also in patients with adverse-risk genetics, without adding toxicity. We performed a post hoc analysis to determine the predictive impact of TP53 status. Despite a nominally higher ORR, the clinically meaningful survival benefit when adding ATRA to DEC was diminished, but not completely negated, in TP53-mutated patients. Indeed, 2 out of 14 TP53-mutated patients (14%) randomized to a DEC + ATRA-containing regimen lived for > 36 months. Further studies of ATRA combined with hypomethylating agents appear warranted in non-M3 AML patients ineligible for HMA/venetoclax therapy. Trial Registration: ClinicalTrials.gov identifier: NCT00867672.

OriginalspracheEnglisch
FachzeitschriftEuropean Journal of Haematology
DOIs
PublikationsstatusAngenommen/Im Druck - 2024

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