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

Publication

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

Journal Paper/Review - Oct 13, 2024

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

Citation

Bresser H, Schmoor C, Grishina O, Pfeifer D, Thomas J, Rehman U, Crysandt M, Jost E, Thol F, Heuser M, Götze K, Schlenk R, Salih H, Schittenhelm M, Heil G, Schwaenen C, Müller-Tidow C, Brugger W, Kuendgen A, de Wit M, Giagounidis A, Scholl S, Neubauer A, Krauter J, Bug G, May A, Wäsch R, Duyster J, Döhner K, Ganser A, Döhner H, Hackanson B, Becker H, Lübbert M. Impact of TP53 Mutation Status in Elderly AML Patients When Adding All-Trans Retinoic Acid or Valproic Acid to Decitabine. Eur J Haematol 2024

Type

Journal Paper/Review (English)

Journal

Eur J Haematol 2024

Publication Date

Oct 13, 2024

Issn Electronic

1600-0609

Brief description/objective

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.