Department of Hematology, Oncology and Stem Cell Transplantation, Faculty of Medicine, University Medical Center Freiburg, Hugstetterstr. 55, 79106, Freiburg, Germany.
Faculty of Medicine, University Medical Center Freiburg, Clinical Trials Unit, Freiburg, Germany.
Clin Epigenetics. 2024 Sep 11;16(1):126. doi: 10.1186/s13148-024-01737-4.
DNA-hypomethylating agents (HMAs) induce notable remission rates in AML/MDS patients with TP53 mutations; however, secondary resistance often develops rapidly. In the DECIDER trial (NCT00867672), elderly AML patients (also those with adverse genetics) randomized to all-trans retinoic acid (ATRA) added to decitabine (DEC) attained significantly delayed time-to-resistance. An 82-year-old patient with a non-disruptive, in-frame TP53 mutation (p.Cys238_Asn239delinsTyr, VAF 90%) and complex-monosomal karyotype attained a complete hematologic and cytogenetic remission with DEC + ATRA, with 3.7 years survival after 30 treatment cycles that were well-tolerated. Further HMA + ATRA studies appear warranted in AML/MDS patients of different genetic risk groups ineligible for more intensive treatment.Trial registration: This trial was registered at ClinicalTrials.gov identifier: NCT00867672.
DNA 低甲基化剂（HMAs）可诱导伴 TP53 突变的 AML/MDS 患者获得显著缓解率；然而，继发耐药通常迅速发展。在 DECIDER 试验（NCT00867672）中，接受全反式维甲酸（ATRA）联合地西他滨（DEC）治疗的老年 AML 患者（也包括具有不良遗传学特征的患者），耐药时间明显延迟。一名 82 岁的患者存在非破坏性、框内 TP53 突变（p.Cys238_Asn239delinsTyr，VAF 90%）和复杂单体核型，接受 DEC+ATRA 治疗后获得完全血液学和细胞遗传学缓解，在接受 30 个周期治疗后 3.7 年仍存活，且耐受良好。对于不适合更强化治疗的不同遗传风险组别的 AML/MDS 患者，进一步开展 HMA+ATRA 研究似乎是合理的。
本试验在 ClinicalTrials.gov 注册号：NCT00867672。
