Venditti Adriano, Hou Jing-Zhou, Fenaux Pierre, Jonas Brian A, Vrhovac Radovan, Montesinos Pau, Garcia Jacqueline S, Rizzieri David, Thirman Michael J, Zhang Meng, Potluri Jalaja, Miller Catherine, Dhalla Mazaher, Pullarkat Vinod
Hematology, Department of Biomedicine and Prevention, University Tor Vergata, Rome, Italy.
Hematology and BMT, Lemieux Center for Blood Cancers, UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Leukemia. 2025 Sep 5. doi: 10.1038/s41375-025-02730-3.
Venetoclax plus azacitidine is recognized as standard of care for patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy (IC). However, some patients may still not be treated with venetoclax combinations due to frailty concerns. We evaluated efficacy and safety of venetoclax plus azacitidine vs. placebo plus azacitidine in patients with newly diagnosed AML ineligible for IC from the phase 3 VIALE-A study (NCT02993523) and the phase 1b M14-358 study (NCT02203773), stratified by two methods to potentially assess frailty. The first method was age-based (75-79, 80-84, ≥85 years; n = 303 pooled from both studies) and the second was fitness-based using the AML composite model (AML-CM), a comorbidity-based model to estimate mortality risk (Group A, B, C; n = 380, from VIALE-A). Efficacy, including composite complete remission and overall survival, were improved with venetoclax plus azacitidine vs. placebo plus azacitidine across age and AML-CM groups. Safety was generally similar between age and AML-CM groups and no new safety signals were identified. Taken together, these data suggest that patients benefit from venetoclax plus azacitidine regardless of age or degree of frailty and the combination may be considered for patients with AML who may be deemed frail. Clinical trial information NCT02993523; NCT02203773.
维奈托克联合阿扎胞苷被公认为是不适用于强化化疗（IC）的急性髓系白血病（AML）患者的标准治疗方案。然而，由于对虚弱状况的担忧，一些患者可能仍未接受维奈托克联合治疗。我们在3期VIALE-A研究（NCT02993523）和1b期M14-358研究（NCT02203773）中，对新诊断的不适用于IC的AML患者，评估了维奈托克联合阿扎胞苷与安慰剂联合阿扎胞苷的疗效和安全性，并通过两种方法进行分层以潜在评估虚弱状况。第一种方法是基于年龄（75 - 79岁、80 - 84岁、≥85岁；两项研究共纳入303例），第二种方法是基于健康状况，使用AML综合模型（AML-CM），这是一种基于合并症的估计死亡风险的模型（A组、B组、C组；来自VIALE-A研究，共380例）。在年龄组和AML-CM组中，与安慰剂联合阿扎胞苷相比，维奈托克联合阿扎胞苷在包括完全缓解和总生存等疗效方面均有改善。年龄组和AML-CM组之间的安全性总体相似，未发现新的安全信号。综上所述，这些数据表明，无论年龄或虚弱程度如何患者均可从维奈托克联合阿扎胞苷治疗中获益，对于可能被视为虚弱的AML患者可考虑使用该联合方案。临床试验信息：NCT02993523；NCT02203773。
