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.

作者：J. Bewersdorf, Tariq Kewan, L. Lanino, Wei Wei, Tulika Rudra Gupta, J. Stempel, N. Al Ali, A. Dezern, M. Sekeres, Geoffrey L Uy, Samuel Urrutia, H. Carraway, Pinkal M. Desai, Elizabeth A. Griffiths, E. Stein, Andrew M. Brunner, Christine M McMahon, R. Shallis, J. Zeidner, M. Savona, Hayley Hawkins, N. Chandhok, Constantine N Logothetis, A. Bidikian, Ted M. Getz, Gail J Roboz, B. Rolles, Eunice S. Wang, Amyah C. Harris, M. Amaya, S. Ball, Justin Grenet, Zhuoer Xie, Y. Madanat, Y. Abaza, T. Badar, Jaclynn Campos, T. Haferlach, J. Maciejewski, D. Sallman, A. Enjeti, Kamal Al-Rabi, K. Halahleh, D. Hiwase, M. Díez-Campelo, David Valcárcel, C. Haferlach, L. Pleyer, Ioannis Kotsianidis, V. Pappa, V. Santini, A. Consagra, A. Al-Kali, Seishi Ogawa, Y. Nannya, Maximilian F. Stahl, M. G. Della Porta, R. Komrokji, A. Zeidan · 发表于：Blood Cancer Journal · 年份：2026 · DOI：10.1038/s41408-026-01543-6 · 被引用次数：1 · 研究领域：Medicine

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.