Impact of <i>TP53</i> Mutation Status in Elderly <scp>AML</scp> Patients When Adding All‐<i>Trans</i> Retinoic Acid or Valproic Acid to Decitabine
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.
Authors
- Johanna Thomas
- Andrea Kündgen
- Dietmar Pfeifer (ORCID: https://orcid.org/0000-0003-2684-5944)
- Arnold Ganser (ORCID: https://orcid.org/0000-0003-3510-4304)
- Carsten Schwäenen
- Heiko Becker (ORCID: https://orcid.org/0000-0002-6919-4048)
- Maike de Wit (ORCID: https://orcid.org/0000-0001-5222-7133)
- Marcus M. Schittenhelm (ORCID: https://orcid.org/0000-0002-5400-5582)
- Sebastian Scholl (ORCID: https://orcid.org/0000-0003-2893-3630)
- Helmut R. Salih (ORCID: https://orcid.org/0000-0002-6719-1847)
- Carsten Müller‐Tidow (ORCID: https://orcid.org/0000-0002-7166-5232)
- Justus Duyster (ORCID: https://orcid.org/0009-0003-1497-3954)
- Aristoteles Giagounidis (ORCID: https://orcid.org/0000-0003-4083-4109)
- Andreas Neubauer (ORCID: https://orcid.org/0000-0002-7606-8760)
- Helena Bresser (ORCID: https://orcid.org/0009-0000-3724-5982)
- Michael Lübbert (ORCID: https://orcid.org/0000-0003-1186-1650)
- Annette M. May (ORCID: https://orcid.org/0000-0002-4337-7081)
- Edgar Jost (ORCID: https://orcid.org/0000-0003-2998-2450)
- Michael Heuser (ORCID: https://orcid.org/0000-0001-5318-9044)
- Richard F. Schlenk (ORCID: https://orcid.org/0000-0003-2215-2059)
- Konstanze Döhner (ORCID: https://orcid.org/0000-0002-2261-9862)
- Felicitas Thol (ORCID: https://orcid.org/0000-0001-5848-6152)
- Usama‐Ur Rehman
- Björn Hackanson (ORCID: https://orcid.org/0000-0001-7242-7503)
- Katharina S. S. Götze (ORCID: https://orcid.org/0000-0002-6276-8002)
- Claudia Schmoor (ORCID: https://orcid.org/0000-0001-5610-9425)
- Gesine Bug (ORCID: https://orcid.org/0000-0003-2359-131X)
- Ralph Wäsch (ORCID: https://orcid.org/0000-0002-0813-3444)
- Hartmut Döhner (ORCID: https://orcid.org/0000-0003-2116-5536)
- Martina Crysandt
- Olga Grishina
- Wolfram Brugger
- Jürgen Krauter
- Gerhard Heil
Institutions
- Goethe University Frankfurt (DE)
- University of Freiburg (DE)
- German Cancer Research Center (DE)
- University of St.Gallen (CH)
- Heidelberg University (DE)
- University Medical Center Freiburg (DE)
- University Hospital Heidelberg (DE)
- TUM Klinikum (DE)
- Medizinische Hochschule Hannover (DE)
- Ortenau Klinikum (DE)
- Nephrologisches Zentrum Villingen-Schwenningen (DE)
- Klinikum Lüdenscheid (DE)
- Vivantes Klinikum (DE)
- National Center for Tumor Diseases (DE)
- Klinikum Braunschweig (DE)
- Universitätsklinikum Aachen (DE)
- University Children's Hospital Tübingen (DE)
- Marien Hospital Düsseldorf (DE)
- Jena University Hospital (DE)
- University Hospital Ulm (DE)
- Heinrich Heine University Düsseldorf (DE)
Publication Details
- Journal
- European Journal Of Haematology
- Published
- 2024-10-13
- DOI
- https://doi.org/10.1111/ejh.14304
- Citations
- 6
- Primary Topic
- Acute Myeloid Leukemia Research
- Type
- article
- Field-Weighted Citation Impact
- 2.73
Funders
- Pfizer
- AstraZeneca