文章：

维奈托克：年轻急性髓系白血病患者治疗领域的革命性突破？

Venetoclax: A Game Changer in the Treatment of Younger AML Patients?

原文发布日期：22 December 2023

DOI: 10.3390/cancers16010073

类型: Article

开放获取: 是

英文摘要：

The combination approach based on venetoclax (VEN) with azacytidine (AZA) has significantly improved outcomes for elderly patients with acute myeloid leukemia (AML). This innovative approach has led to higher rates of overall response, measurable residual disease (MRD)-negative remissions, and overall survival compared with AZA monotherapy. As a result, this combination has emerged as the gold-standard treatment for elderly or unfit patients with AML who are not eligible for intensive therapy. In younger, fit patients with AML, intensive induction and consolidation chemotherapy is commonly used as a first-line approach; however, relapse continues to be the main reason for treatment failure in approximately 30–40% of patients. Efforts to improve MRD-negative response rates and to facilitate the transition to allogeneic hematopoietic stem cell transplantation, particularly in high-risk AML, have inspired trials exploring the combination of intensive chemotherapy with targeted agents. VEN, a first-in-class anti-BCL2 agent, combined with intensive chemotherapy regimens has shown deep MRD-negative remissions, producing prolonged event-free survival and enhancing the transition to allogeneic transplant in first-complete-remission patients. These benefits support the incremental advantages of adding VEN to intensive chemotherapy approaches across ELN risk subcategories, and provides a robust benchmark to design future trials. In this review, we will discuss current studies assessing the efficacy of frontline regimens integrating VEN into intensive chemotherapy in younger patients with AML and specific molecularly defined subgroups.

摘要翻译： 

基于维奈托克（VEN）与阿扎胞苷（AZA）的联合治疗方案显著改善了老年急性髓系白血病（AML）患者的预后。与AZA单药治疗相比，这一创新方案带来了更高的总体缓解率、可测量残留病（MRD）阴性缓解率以及总生存率。因此，该联合方案已成为不适合强化治疗的老年或不耐受AML患者的标准治疗方案。对于年轻、耐受性良好的AML患者，强化诱导和巩固化疗通常作为一线治疗方案；然而，复发仍是约30-40%患者治疗失败的主要原因。为提高MRD阴性缓解率并促进向异基因造血干细胞移植过渡，尤其是在高危AML患者中，研究者尝试探索强化化疗与靶向药物的联合应用。维奈托克作为首创的BCL2抑制剂，与强化化疗方案联合应用已显示出深度MRD阴性缓解效果，延长了无事件生存期，并促进了首次完全缓解患者向异基因移植的过渡。这些优势支持了在强化化疗方案中加入VEN在ELN风险亚组中的累积获益，并为未来试验设计提供了坚实基准。本综述将讨论当前关于VEN联合强化化疗作为年轻AML患者及特定分子定义亚组一线治疗方案疗效评估的研究进展。

原文链接：

Venetoclax: A Game Changer in the Treatment of Younger AML Patients?