Kretschmer Lydia, Ruhnke Leo, Schliemann Christoph, Fransecky Lars, Steffen Björn, Kaufmann Martin, Burchert Andreas, Schmid Christoph, Hanoun Maher, Sauer Tim, Metzeler Klaus H, Schäfer-Eckart Kerstin, Hänel Mathias, Crysandt Martina, Jäger Paul, Krause Stefan W, Dierks Christine, Klein Stefan, Maguire Nadia, Frenzel Lukas P, Bücklein Veit L, Blau Wolfgang, Kaiser Ulrich, Wegehenkel Kai, Höllein Alexander, Seggewiss-Bernhardt Ruth, Markgraf Wenke, Fiebig Frank, Harig Anna, Schmidt-Brücken Katharina, Thiede Christian, Middeke Jan Moritz, Dillon Richard, Baldus Claudia D, Serve Hubert, Spiekermann Karsten, Hiddemann Wolfgang, Schlenk Richard F, Müller-Tidow Carsten, Bornhäuser Martin, Röllig Christoph
Department of Internal Medicine I, University Hospital Dresden, TU Dresden, Fetscherstraße 74, Dresden, 01307, Germany.
Department of Medicine A, University Hospital Münster, Münster, Germany.
Ann Hematol. 2025 Jul 9. doi: 10.1007/s00277-025-06496-7.
For younger, medically fit patients with NPM1-mutated, FLT3-wildtype acute myeloid leukemia (AML) intensive chemotherapy represents standard of care (SOC), with complete remission (CR) rates observed in up to 85% of patients and 5-year overall survival (OS) rates of 40-50%. However, significant toxicity and need for hospitalization pose challenges on patients' outcome and quality of life (QoL). Venetoclax (VEN) combined with azacitidine (AZA) has demonstrated encouraging efficacy in older, unfit AML patients, achieving high CR/CRi rates and promising OS with lower toxicity. Prospective, randomized data comparing VEN/AZA to SOC in younger, fit patients are currently missing. VINCENT is a randomized-controlled, multicenter, non-inferiority, phase 2 trial (NCT05904106) evaluating VEN/AZA versus SOC in adults aged 18-70 years with newly diagnosed, NPM1-mutated, FLT3-wildtype AML. Patients medically fit for intensive chemotherapy (ECOG ≤ 2) with adequate organ function are eligible, while patients with relapsed/refractory AML or prior cytotoxic treatment are excluded. A total of 146 patients will be randomized 1:1 to receive either VEN/AZA or SOC. Hematologic remission is evaluated according to ELN 2022 guidelines. The primary endpoint is the modified event-free survival, defined as either primary induction failure, hematologic relapse, molecular failure or death. Secondary endpoints include safety, tolerability, CR/CRi/CRh/CR rates, MRD kinetics (using NPM1 RT-qPCR and MFC), relapse-free survival, OS, early mortality, health-related QoL and cumulative health-care-resource use. Patients will be followed up for at least two years post enrollment. The VINCENT trial will be the first study to provide comprehensive prospective data comparing VEN/AZA to SOC, addressing both efficacy and patient-centered outcomes.
对于年龄较轻、身体状况适合的NPM1突变、FLT3野生型急性髓系白血病（AML）患者，强化化疗是标准治疗方案（SOC），高达85%的患者可实现完全缓解（CR），5年总生存率（OS）为40%-50%。然而，显著的毒性和住院需求对患者的预后和生活质量（QoL）构成挑战。维奈克拉（VEN）联合阿扎胞苷（AZA）在年龄较大、身体状况不佳的AML患者中已显示出令人鼓舞的疗效，可实现高CR/CRi率，并有望降低毒性实现OS。目前尚缺乏在年龄较轻、身体状况适合的患者中比较VEN/AZA与SOC的前瞻性随机数据。VINCENT是一项随机对照、多中心、非劣效性2期试验（NCT05904106），评估VEN/AZA与SOC在18-70岁新诊断的NPM1突变、FLT3野生型AML成人患者中的疗效。身体状况适合接受强化化疗（东部肿瘤协作组体能状态评分≤2）且器官功能良好的患者符合条件，而复发性/难治性AML患者或先前接受过细胞毒性治疗的患者被排除。总共146名患者将按1:1随机分组，接受VEN/AZA或SOC治疗。根据欧洲白血病网（ELN）2022指南评估血液学缓解情况。主要终点是改良无事件生存期，定义为原发性诱导失败、血液学复发、分子学失败或死亡。次要终点包括安全性、耐受性、CR/CRi/CRh/CR率、微小残留病动力学（使用NPM1逆转录定量聚合酶链反应和多参数流式细胞术）、无复发生存期、OS、早期死亡率、健康相关生活质量和累积医疗资源使用情况。患者入组后将至少随访两年。VINCENT试验将是第一项提供全面前瞻性数据比较VEN/AZA与SOC的研究，涉及疗效和以患者为中心的结局。
