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 R, Schittenhelm Marcus M, Heil Gerhard, Schwaenen Carsten, Müller-Tidow Carsten, Brugger Wolfram, Kündgen Andrea, de Wit Maike, 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
Department of Hematology, Oncology and Stem Cell Transplantation, University Medical Center Freiburg, Faculty of Medicine, Freiburg, Germany.
Clinical Trials Unit, University Medical Center Freiburg, Freiburg, Germany.
Eur J Haematol. 2025 Feb;114(2):231-237. doi: 10.1111/ejh.14304. Epub 2024 Oct 13.
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.
在一项针对老年新诊断急性髓系白血病（AML）患者的随机II期试验（AMLSG 14 - 09，NCT00867672）中，全反式维甲酸（ATRA）联合地西他滨（DEC）显著提高了总体缓解率（ORR），对于具有不良风险遗传学特征的患者，其生存情况也得到改善，且未增加毒性。我们进行了一项事后分析以确定TP53状态的预测影响。在TP53突变患者中，尽管名义上ORR较高，但在DEC基础上加用ATRA时具有临床意义的生存获益有所减少，但并未完全消除。实际上，在随机分配至含DEC + ATRA方案的14例TP53突变患者中，有2例（14%）存活超过36个月。对于不符合HMA/维奈克拉治疗条件的非M3 AML患者，进一步研究ATRA联合低甲基化药物似乎是有必要的。试验注册：ClinicalTrials.gov标识符：NCT00867672。
