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
Year: 2026
Type: article
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.
Source: Blood Cancer Journal
Authors: 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
Institutions: Yale Cancer Center, Yale University, Moffitt Cancer Center, Johns Hopkins University, Sidney Kimmel Comprehensive Cancer Center, University of Miami, Sylvester Comprehensive Cancer Center, Washington University in St. Louis, Cleveland Clinic, Weill Cornell Medicine, Roswell Park Comprehensive Cancer Center, Memorial Sloan Kettering Cancer Center, Harvard University, Massachusetts General Hospital, University of North Carolina at Chapel Hill, UNC Lineberger Comprehensive Cancer Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Harold C. Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Northwestern University, Mayo Clinic in Florida, Munich Leukemia Laboratory (Germany), Calvary Mater Newcastle Hospital, King Hussein Cancer Center, Royal Adelaide Hospital, Universidad de Salamanca, Vall d'Hebron Hospital Universitari, Paracelsus Medical University, Democritus University of Thrace, National and Kapodistrian University of Athens, University General Hospital Attikon, Azienda Ospedaliero-Universitaria Careggi, University of Florence, Mayo Clinic, Kyoto University, Kindai University, The University of Tokyo, Humanitas University, IRCCS Humanitas Research Hospital
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,290
Awards: G1165031887, G1226504839, G1324270360, Synthetic Data Generation Framework for Integrated Validation of Use Cases and AI Healthcare Applications, Genomics and Personalized Medicine for all though Artificial Intelligence in Haematological Diseases, Understanding of clonal evolution in cancer and normal tissues, G4458620078, Comprehensive methodological and operational approach to clinical trials in rare and ultra-rare diseases, G8828857581
OpenAlex ID: W7166509397