BCL2 抑制剂 Venetoclax 已显示出治疗急性髓系白血病 (AML) 的前景。然而，确定可能有反应的患者仍然是一个挑战，特别是对于那些患有复发/难治性 (R/R) 疾病的患者。我们在芬兰 AML 小组（VenEx，NCT04267081）进行的一项前瞻性、多中心、2 期试验中评估了离体 Venetoclax 敏感性测试在预测 Venetoclax-azacitidine 治疗反应方面的效用。该试验招募了 104 名既往未接受治疗 (n=48)、R/R (n=39) 或既往接受过继发性 AML (sAML) (n=17) 治疗的参与者。主要终点是前三个治疗周期中离体敏感试验参与者的完全缓解或完全缓解伴不完全血液学恢复 (CR/CRi) 率。关键的次要终点包括离体药物敏感性、反应和生存之间的相关性。成功评估了 102/104 名参与者的 Venetoclax 敏感性，结果在采样后平均三天内即可获得。在先前未经治疗的 AML 中，离体敏感性相当于 85% (34/40) CR/CRi 率，中位总生存期 (OS) 为 28.7 个月，而离体耐药患者为 5.5 个月 (p = 0.002)。对于 R/R/sAML，离体敏感性导致 62% CR/CRi 率 (21/34)，中位 OS 为 9.7，而离体耐药患者为 3.3 个月 (p < 0.001)。在单变量和多变量分析中，离体 Venetoclax 敏感性是良好治疗反应和生存的最强预测因子。 VenEx 试验证明了将离体药物测试整合到临床实践中以识别 AML 患者的可行性，特别是在 R/R 环境中，谁受益于 venetoclax。版权所有 © 2024 美国血液学会。

The BCL2 inhibitor venetoclax has shown promise for treating acute myeloid leukemia (AML). However, identifying patients likely to respond remains a challenge, especially for those with relapsed/refractory (R/R) disease. We evaluated the utility of ex vivo venetoclax sensitivity testing to predict treatment responses to venetoclax-azacitidine in a prospective, multicenter, phase 2 trial conducted by the Finnish AML Group (VenEx, NCT04267081). The trial recruited 104 participants with previously untreated (n=48), R/R (n=39) or previously treated secondary AML (sAML) (n=17). The primary endpoint was complete remission or complete remission with incomplete hematologic recovery (CR/CRi) rate in ex vivo sensitive trial participants during the first three therapy cycles. The key secondary endpoints included the correlations between ex vivo drug sensitivity, responses, and survival. Venetoclax sensitivity was successfully assessed in 102/104 participants, with results available within a median of three days from sampling. In previously untreated AML, ex vivo sensitivity corresponded to an 85% (34/40) CR/CRi rate, with a median overall survival (OS) of 28.7 months, compared to 5.5 months for ex vivo resistant patients (p = 0.002). For R/R/sAML, ex vivo sensitivity resulted in a 62% CR/CRi rate (21/34) and median OS of 9.7 versus 3.3 months for ex vivo resistant patients (p < 0.001). In univariate and multivariate analysis, ex vivo venetoclax sensitivity was the strongest predictor for a favorable treatment response and survival. The VenEx trial demonstrates the feasibility of integrating ex vivo drug testing into clinical practice to identify AML patients, particularly in the R/R setting, who benefit from venetoclax.Copyright © 2024 American Society of Hematology.