Jan Philipp Bewersdorf, Tariq Kewan, Luca Lanino, Wei Wei, Tulika R. Gupta, Jessica M. Stempel, Najla H. Al Ali, Amy E. DeZern, M. Sekeres, Geoffrey L. Uy, Samuel Urrutia, Hetty E. Carraway, P Desai, Elizabeth A. Griffiths, Eytan M. Stein, Andrew M. Brunner, Christine McMahon, Rory M. Shallis, Joshua F. Zeidner, Michael R. Savona, Hayley Hawkins, Namrata S. Chandhok, Constantine N. Logothetis, Aram Bidikian, Ted M. Getz, Gail J. Roboz, Benjamin Rolles, Eunice S. Wang, Abi 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 A. Sallman, Anoop Enjeti, Kamal Al-Rabi, Khalid Halahleh, Devendra Hiwase, María Díez‐Campelo, David Valcárcel, Claudia Haferlach, Lisa Pleyer, Ιoannis Kotsianidis, Vasiliki Pappa, Valeria Santini, Angela Consagra, Aref Al-Kali, Seishi Ogawa, Yasuhito Nannya, Maximilian Stahl, Matteo Giovanni Della Porta, Rami S. Komrokji, Amer M. Zeidan
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.