阿扎胞苷与维奈克拉联合或不联合pevonedistat用于新诊断的急性髓系白血病患者。

Azacitidine and venetoclax with or without pevonedistat in patients with newly diagnosed acute myeloid leukemia.

作者信息

Short Nicholas J, Wierzbowska Agnieszka, Cluzeau Thomas, Laribi Kamel, Recher Christian, Czyz Jaroslaw, Ochrem Bogdan, Ades Lionel, Gallego-Hernanz Maria Pilar, Heiblig Mael, Audisio Ernesta, Zarzycka Ewa, Li Shuli, Ferenc Nicholas, Yeh Tammie, Faller Douglas V, Sedarati Farhad, Papayannidis Cristina

机构信息

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Department of Hematology, Medical University of Lodz, Lodz, Poland.

出版信息

Leuk Lymphoma. 2025 Mar;66(3):458-468. doi: 10.1080/10428194.2024.2431878. Epub 2024 Nov 28.

DOI:10.1080/10428194.2024.2431878

PMID:39606906

Abstract

UNLABELLED

This phase 2 study investigated pevonedistat + azacitidine + venetoclax ( = 83) versus azacitidine + venetoclax ( = 81) in patients with newly diagnosed acute myeloid leukemia (AML) ineligible for intensive chemotherapy. The study was stopped early following negative results from PANTHER, which evaluated pevonedistat in higher-risk myelodysplastic syndromes/chronic myelomonocytic leukemia or low-blast AML. Outcomes were analyzed up to the datacut. For pevonedistat + azacitidine + venetoclax versus azacitidine + venetoclax, the median follow-up was 8.44 versus 7.95 months; the complete remission (CR) rate was 45% versus 49%; composite CR (CCR; CR+CR with incomplete blood count recovery) was 77% versus 72%. There were no differences in event-free survival (primary endpoint; hazard ratio [HR]: 0.99; 95% confidence interval [CI]: 0.61-1.60; = 0.477) or overall survival (HR: 1.42; 95% CI: 0.82-2.49; = 0.896). In exploratory analyses in -mutated AML, CCR rates were higher with pevonedistat + azacitidine + venetoclax versus azacitidine + venetoclax. Safety was similar between treatment arms. Efficacy/safety with azacitidine + venetoclax was consistent with the phase 3 VIALE-A study.

TRIAL REGISTRATION

NCT04266795.

摘要

未标记

本2期研究在不符合强化化疗条件的新诊断急性髓系白血病（AML）患者中，对比了pevonedistat联合阿扎胞苷和维奈克拉（n = 83）与阿扎胞苷和维奈克拉（n = 81）的疗效。在对pevonedistat用于高危骨髓增生异常综合征/慢性粒单核细胞白血病或低原始细胞AML进行评估的PANTHER研究得出阴性结果后，该研究提前终止。对数据截止时的结果进行了分析。对于pevonedistat联合阿扎胞苷和维奈克拉与阿扎胞苷和维奈克拉，中位随访时间分别为8.44个月和7.95个月；完全缓解（CR）率分别为45%和49%；复合完全缓解（CCR；CR + 血细胞计数未完全恢复的CR）率分别为77%和72%。无事件生存期（主要终点；风险比[HR]：0.99；95%置信区间[CI]：0.61 - 1.60；P = 0.477）或总生存期（HR：1.42；95% CI：0.82 - 2.49；P = 0.896）无差异。在对FLT3突变的AML进行的探索性分析中，pevonedistat联合阿扎胞苷和维奈克拉的CCR率高于阿扎胞苷和维奈克拉。各治疗组之间的安全性相似。阿扎胞苷和维奈克拉的疗效/安全性与3期VIALE - A研究一致。