Hematology Department, University Hospital of Nice, Cote d'Azur University, 06200 Nice, France.
INSERM U1065, Mediterranean Center of Molecular Medicine, Cote d'Azur University, 06200 Nice, France.
Int J Mol Sci. 2021 Sep 18;22(18):10105. doi: 10.3390/ijms221810105.
Targeting TP53 mutated myelodysplastic syndromes and acute myeloid leukemia remains a significant unmet need. Recently, new drugs have attempted to improve the outcomes of this poor molecular subgroup. The aim of this article is to review all the current knowledge using active agents including hypomethylating agents with venetoclax, eprenetapopt or magrolimab. We include comprehensive analysis of clinical trials to date evaluating these drugs in TP53 myeloid neoplasms as well as discuss future novel combinations for consideration. Additionally, further understanding of the unique clinicopathologic components of TP53 mutant myeloid neoplasms versus wild-type is critical to guide future study. Importantly, the clinical trajectory of patients is uniquely tied with the clonal burden of TP53, which enables serial TP53 variant allele frequency analysis to be a critical early biomarker in investigational studies. Together, significant optimism is now possible for improving outcomes in this patient population.
针对 TP53 突变性骨髓增生异常综合征和急性髓系白血病仍然是一个重大的未满足的需求。最近，新的药物已经尝试改善这一不良分子亚组的预后。本文的目的是使用包括与 venetoclax、eprinetapopt 或 magrolimab 联合的低甲基化剂在内的现有活性药物，综述所有目前的知识。我们包括对迄今为止评估这些药物在 TP53 髓系肿瘤中的临床试验的综合分析，并讨论未来可考虑的新联合用药方案。此外，进一步了解 TP53 突变性髓系肿瘤与野生型之间独特的临床病理成分对于指导未来的研究至关重要。重要的是，患者的临床病程与 TP53 的克隆负担密切相关，这使得连续的 TP53 变异等位基因频率分析成为研究中一个关键的早期生物标志物。总的来说，现在有可能改善这一患者群体的预后。
