Impact of TP53 Mutation Status in Elderly AML Patients When Adding All‐ Trans Retinoic Acid or Valproic Acid to Decitabine
Year: 2024
Type: article
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.
Source: European Journal Of Haematology
DOI: 10.1111/ejh.14304
Authors: 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 Wit, Aristoteles 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
Institutions: University of Freiburg, University Medical Center Freiburg, Universitätsklinikum Aachen, RWTH Aachen University, Medizinische Hochschule Hannover, German Cancer Research Center, TUM Klinikum, Deutsches Konsortium für Translationale Krebsforschung, Technical University of Munich, Heidelberg University, University Hospital Heidelberg, National Center for Tumor Diseases, Universitätsklinikum Tübingen, University of Tübingen, Kantonsspital St. Gallen, Klinikum Lüdenscheid, Ortenau Klinikum, Schwarzwald-Baar Klinikum, Heinrich Heine University Düsseldorf, Vivantes Klinikum, Marien Hospital Düsseldorf, Jena University Hospital, Philipps University of Marburg, Klinikum Braunschweig, Goethe University Frankfurt, University Hospital Ulm, University of Augsburg, University Hospital Augsburg
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,430
Funders: Pfizer, AstraZeneca
OpenAlex ID: W4403405039