Background: Acute myeloid leukemia (AML) harboring NPM1 mutations constitutes a biologically and clinically distinct subtype, characterized by marked sensitivity to inhibition of the anti-apoptotic proteinBCL-2. The introduction of venetoclax, a selective BCL-2 inhibitor, in combination with hypomethylating agents (HMAs), has reshaped the therapeutic paradigm, particularly for patients deemed unfit for intensive chemotherapy. Materials and Methods: This review comprehensively analyzes the available scientific evidence—including prospective clinical trials, retrospective cohorts, and real-world studies—to summarize current knowledge on the efficacy, safety, and therapeutic role of venetoclax-based regimens in NPM1-mutated AML. Results and Discussion: Accumulating data demonstrate that venetoclax combined with HMAs achieves high rates of deep molecular remission and significantly improves overall survival in patients with NPM1-mutated AML. Despite these advances, important questions remain regarding the optimal duration of therapy, as well as timing and criteria for treatment discontinuation. Minimal residual disease monitoring is emerging as a pivotal tool to guide therapeutic decisions and enable personalized treatment strategies. Conclusions: Venetoclax-based regimens represent a major advancement in the treatment of NPM1-mutated AML, promoting a shift toward more targeted and less toxic therapeutic approaches. Nonetheless, prospective randomized trials are required to establish standardized clinical algorithms and to refine maintenance and discontinuation strategies, with the ultimate goal of improving patient quality of life and long-term outcomes.
背景：携带NPM1突变的急性髓系白血病（AML）构成一个生物学和临床特征独特的亚型，其特点是对抗凋亡蛋白BCL-2的抑制具有显著敏感性。选择性BCL-2抑制剂维奈克拉联合去甲基化药物的应用，重塑了该疾病的治疗范式，尤其为不适合强化化疗的患者提供了新选择。材料与方法：本综述系统分析现有科学证据——包括前瞻性临床试验、回顾性队列研究和真实世界研究——旨在总结维奈克拉为基础的治疗方案在NPM1突变AML中的疗效、安全性及治疗作用的当前认知。结果与讨论：现有数据表明，维奈克拉联合去甲基化药物能在NPM1突变AML患者中获得较高的深度分子学缓解率，并显著改善总生存期。尽管取得这些进展，关于最佳治疗时长、治疗中止时机及标准等重要问题仍有待明确。微小残留病监测正逐渐成为指导治疗决策、实现个体化治疗策略的关键工具。结论：以维奈克拉为基础的治疗方案代表了NPM1突变AML治疗领域的重大进展，推动治疗模式向更具靶向性、更低毒性的方向转变。然而，仍需开展前瞻性随机试验以建立标准化临床路径，优化维持治疗及治疗中止策略，最终实现改善患者生活质量和长期预后的目标。
Harnessing Venetoclax in NPM1-Mutated AML: A Path to Sustained Remission and Beyond
肿瘤(癌症)患者之家