Outcomes of patients with higher-risk myelodysplastic syndromes/neoplasms treated with hypomethylating agents + venetoclax-an analysis from the International Consortium for MDS (icMDS) VALIDATE database.

IF 13.8 1区医学 Q1 HEMATOLOGY

Blood Cancer Journal Pub Date : 2026-06-29 DOI:10.1038/s41408-026-01543-6

Jan Philipp Bewersdorf,Tariq Kewan,Luca Lanino,Wei Wei,Tulika Rudra Gupta,Jessica M Stempel,Najla H Al Ali,Amy E DeZern,Mikkael A Sekeres,Geoffrey L Uy,Samuel Urrutia,Hetty E Carraway,Pinkal Desai,Elizabeth A Griffiths,Eytan M Stein,Andrew M Brunner,Christine McMahon,Rory M Shallis,Joshua F Zeidner,Michael R Savona,Hayley Hawkins,Namrata Sonia Chandhok,Constantine N Logothetis,Aram Bidikian,Ted M Getz,Gail J Roboz,Benjamin Rolles,Eunice S Wang,Amyah C Harris,Maria L Amaya,Somedeb Ball,Justin Grenet,Zhuoer Xie,Yazan F Madanat,Yasmin Abaza,Talha Badar,Jaclynn Campos,Torsten Haferlach,Jaroslaw P Maciejewski,David Sallman,Anoop Enjeti,Kamal Al-Rabi,Khalid Halahleh,Devendra Hiwase,Maria Diez-Campelo,David Valcarcel,Claudia Haferlach,Lisa Pleyer,Ioannis Kotsianidis,Vassiliki Pappa,Valeria Santini,Angela Consagra,Aref Al-Kali,Seishi Ogawa,Yasuhito Nannya,Maximilian Stahl,Matteo Giovanni Della Porta,Rami S Komrokji,Amer M Zeidan

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引用次数: 0

Abstract

Monotherapy with hypomethylating agents (HMA) remains the standard of care for patients with higher-risk myelodysplastic neoplasms (HR-MDS). Recently, the randomized phase III VERONA study evaluating azacitidine plus venetoclax (VEN) versus azacitidine plus placebo in newly diagnosed HR-MDS showed no difference in overall survival (OS) between the two arms. However, whether the addition of VEN to HMA improves outcomes among subsets of patients with HR-MDS remains debated. We analyzed 1907 patients with HR-MDS from 31 centers in 9 countries who were treated with HMA monotherapy or HMA/VEN in the frontline setting (HMA monotherapy: n = 1773; HMA/VEN: n = 134). Responses were assessed centrally by two investigators using the IWG 2023 response criteria. Addition of VEN improved composite complete remission (cCR) rates (48.8% vs. 27.7%; p < 0.001) but not CR rates (17.1% vs. 11.7%; p = 0.16). In multivariable logistic regression analysis, cCR remained favorable for HMA/VEN vs. HMA monotherapy (Odds Ratio [OR]: 2.49; 95% CI: 1.56-3.96; p < 0.001). However, we did not observe a statistically significant difference in OS for HMA/VEN vs. HMA monotherapy (Hazard Ratio [HR]: 0.83; 95% CI: 0.64-1.07; p = 0.15). In subgroup analyses, patients with TP53 wild-type disease (HR: 0.47; 95% CI: 0.29-0.74; p = 0.002) had a significant improvement in OS and those with ≥10% bone marrow blasts (HR: 0.73; 95% CI: 0.53-1.01; p = 0.06) had a trend towards OS benefit with HMA/VEN.

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低甲基化药物+ venetoclax治疗高风险骨髓增生异常综合征/肿瘤患者的结局——来自国际MDS联盟（icMDS） VALIDATE数据库的分析

低甲基化药物（HMA）的单药治疗仍然是高风险骨髓增生异常肿瘤（HR-MDS）患者的标准治疗方法。最近，一项随机III期VERONA研究评估了阿扎胞苷加venetoclax （VEN）与阿扎胞苷加安慰剂对新诊断的HR-MDS的治疗效果，结果显示两组患者的总生存期（OS）没有差异。然而，在HMA中加入VEN是否能改善HR-MDS患者亚群的预后仍存在争议。我们分析了来自9个国家31个中心的1907例HR-MDS患者，他们在一线接受HMA单药治疗或HMA/VEN治疗（HMA单药治疗：n = 1773; HMA/VEN: n = 134）。两名调查人员使用IWG 2023响应标准对响应进行集中评估。添加VEN可改善综合完全缓解（cCR）率（48.8% vs. 27.7%, p < 0.001），但不能改善CR率（17.1% vs. 11.7%, p = 0.16）。在多变量logistic回归分析中，HMA/VEN与HMA单药治疗的cCR仍然有利（优势比[OR]: 2.49; 95% CI: 1.56-3.96; p < 0.001）。然而，我们没有观察到HMA/VEN与HMA单药治疗的OS有统计学差异（风险比[HR]: 0.83; 95% CI: 0.64-1.07; p = 0.15）。在亚组分析中，TP53野生型疾病患者（HR: 0.47; 95% CI: 0.29-0.74; p = 0.002）的OS有显著改善，骨髓原细胞≥10%的患者（HR: 0.73; 95% CI: 0.53-1.01; p = 0.06） HMA/VEN的OS有改善的趋势。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Blood Cancer Journal ONCOLOGY-

CiteScore

16.70

自引率

2.30%

发文量

153

审稿时长

>12 weeks

期刊介绍： Blood Cancer Journal is dedicated to publishing high-quality articles related to hematologic malignancies and related disorders. The journal welcomes submissions of original research, reviews, guidelines, and letters that are deemed to have a significant impact in the field. While the journal covers a wide range of topics, it particularly focuses on areas such as: Preclinical studies of new compounds, especially those that provide mechanistic insights Clinical trials and observations Reviews related to new drugs and current management of hematologic malignancies Novel observations related to new mutations, molecular pathways, and tumor genomics Blood Cancer Journal offers a forum for expedited publication of novel observations regarding new mutations or altered pathways.