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

IF 2.3 3区医学 Q2 HEMATOLOGY

European Journal of Haematology Pub Date : 2024-10-13 DOI:10.1111/ejh.14304

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

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引用次数: 0

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.

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在地西他滨基础上加用全反式维甲酸或丙戊酸时TP53突变状态对老年急性髓细胞白血病患者的影响

在一项针对老年新诊断急性髓细胞白血病患者的随机II期试验（AMLSG 14-09，NCT00867672）中，ATRA联合地西他滨（DEC）在不增加毒性的情况下显著提高了不良风险遗传学患者的总反应率（ORR）和生存率。我们进行了一项事后分析，以确定 TP53 状态的预测影响。尽管TP53基因突变患者的总体反应率（ORR）名义上更高，但在DEC中加入ATRA后，TP53基因突变患者有临床意义的生存期获益有所减少，但并未完全消失。事实上，在随机接受 DEC + ATRA 方案治疗的 14 例 TP53 突变患者中，有 2 例（14%）的生存期超过了 36 个月。对于不符合HMA/venetoclax治疗条件的非M3 AML患者，似乎有必要进一步研究ATRA与低甲基化药物的联合治疗。试验注册：ClinicalTrials.gov 标识符：NCT00867672：NCT00867672。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

European Journal of Haematology 医学-血液学

CiteScore

5.50

自引率

0.00%

发文量

168

审稿时长

4-8 weeks

期刊介绍： European Journal of Haematology is an international journal for communication of basic and clinical research in haematology. The journal welcomes manuscripts on molecular, cellular and clinical research on diseases of the blood, vascular and lymphatic tissue, and on basic molecular and cellular research related to normal development and function of the blood, vascular and lymphatic tissue. The journal also welcomes reviews on clinical haematology and basic research, case reports, and clinical pictures.