Farina Mirko, Malagola Michele, Bernardi Simona, Re Federica, Russo Domenico, Avenoso Daniele
Unit of Blood Diseases and Bone Marrow Transplantation, Department of Clinical and Experimental Science, University of Brescia, ASST Spedali Civili di Brescia, 25123 Brescia, Italy.
J Clin Med. 2025 Apr 17;14(8):2759. doi: 10.3390/jcm14082759.
Acute myeloid leukemia (AML) primarily affects older adults and is associated with poor prognosis, particularly in patients aged ≥ 60 years with comorbidities and adverse disease characteristics. Standard intensive chemotherapy, such as the "7 + 3" regimen, has shown limited efficacy and substantial toxicity in this population, underscoring the need for alternative treatment strategies. In recent years, venetoclax-based regimens have emerged as an important option, demonstrating promising outcomes in elderly patients traditionally considered unfit for intensive therapy and, more recently, even in selected fit patients. This narrative review provides a comprehensive comparative analysis of intensive chemotherapy and venetoclax-based regimens in elderly AML patients. This review synthesizes evidence from prospective and retrospective clinical trials, with focuses on treatment efficacy, safety, and the ability to bridge patients to curative allogeneic hematopoietic stem cell transplantation (allo-HSCT). Intensive chemotherapy has achieved complete remission (CR) rates of 40-60% in elderly AML patients, though the median overall survival (OS) rarely exceeds 12 months. Conversely, venetoclax combined with hypomethylating agents has recently demonstrated CR rates of up to 74%, with 83% of responders proceeding to allo-HSCT in selected studies. Venetoclax-based regimens have also been associated with improved tolerability and reduced treatment-related mortality. This review highlights a paradigm shift in the management of AML in the elderly. While intensive chemotherapy remains a standard option for selected patients, the increasing use of venetoclax-based regimens represents a novel and effective strategy with the potential to overcome traditional limitations, especially in patients previously deemed ineligible for curative approaches. The high remission and transplantation rates observed with non-intensive therapies support their role not only as a palliative alternative but as a bridge to cure. Venetoclax-based regimens are reshaping the treatment landscape of AML in the elderly, offering high response rates and facilitating access to allo-HSCT. Further research is needed to optimize treatment sequencing, explore novel combinations, and reduce relapse rates after transplants, ultimately improving the long-term outcomes in this high-risk population.
急性髓系白血病（AML）主要影响老年人，且预后较差，尤其是在年龄≥60岁且伴有合并症及不良疾病特征的患者中。标准的强化化疗，如“7 + 3”方案，在该人群中疗效有限且毒性较大，这凸显了采用替代治疗策略的必要性。近年来，基于维奈克拉的方案已成为一个重要选择，在传统上被认为不适合强化治疗的老年患者中显示出了有前景的结果，并且最近在部分合适的患者中也取得了良好效果。本叙述性综述对老年AML患者的强化化疗和基于维奈克拉的方案进行了全面的比较分析。该综述综合了前瞻性和回顾性临床试验的证据，重点关注治疗效果、安全性以及将患者过渡到根治性异基因造血干细胞移植（allo-HSCT）的能力。强化化疗在老年AML患者中实现了40% - 60%的完全缓解（CR）率，不过中位总生存期（OS）很少超过12个月。相反，维奈克拉联合去甲基化药物最近显示出高达74%的CR率，在部分研究中83%的缓解者接受了allo-HSCT。基于维奈克拉的方案还与耐受性改善及治疗相关死亡率降低有关。本综述强调了老年AML管理中的范式转变。虽然强化化疗仍然是部分患者的标准选择，但基于维奈克拉的方案的使用日益增加代表了一种新颖且有效的策略，有可能克服传统局限性，尤其是在先前被认为不适合根治性治疗方法的患者中。非强化治疗所观察到的高缓解率和移植率不仅支持其作为姑息性替代方案的作用，还支持其作为治愈桥梁的作用。基于维奈克拉的方案正在重塑老年AML的治疗格局，提供高缓解率并促进allo-HSCT的实施。需要进一步研究以优化治疗顺序、探索新的联合方案并降低移植后的复发率，最终改善这一高危人群的长期结局。
