Subgroup analyses from the randomized, Phase 3 VERONA study of venetoclax with azacitidine (Ven+Aza) versus placebo with azacitidine (Pbo+Aza) in patients with treatment-naïve, intermediate and higher-risk Myelodysplastic Syndromes (HR MDS)

作者：Guillermo Garcia‐Manero, Uwe Platzbecker, Pierre Fenaux, G. Roboz, Chun Yew Fong, Marek Hus, Robert Delage, Andrew M. Brunner, Je‐Hwan Lee, Mehmet Turgut, Dominiek Mazure, Yin‐Hsun Feng, Yasushi Miyazaki, Zdeněk Kořı́stek, Sophie Dimicoli Salazar, Stefania Paolini, María Diez‐Campelo, David Lavie, Dominic Culligan, Grace Ku, Zhijian Xiao, Fang Fang, Maggie Headley, Jalaja Potluri, Amer M. Zeidan, Jacqueline S. Garcia · 发表于：Blood · 年份：2025 · DOI：10.1182/blood-2025-235 · 被引用次数：6 · 研究领域：Acute Myeloid Leukemia Research、Myeloproliferative Neoplasms: Diagnosis and Treatment、Hematopoietic Stem Cell Transplantation

Abstract Background: Patients with HR MDS face poor prognosis and are often ineligible for hematopoietic cell transplantation (HCT). After encouraging safety and efficacy in a phase 1b study (Garcia Blood 2025), Ven+Aza was evaluated against Pbo+Aza in patients with treatment-naïve HR MDS in the randomized, phase 3 VERONA study (NCT04401748). Primary analysis at 41.2 months median follow-up showed no difference in overall survival (OS) with Ven+Aza (22.18 mo) vs Pbo+Aza (21.68 mo; HR=0.908 [95% CI, 0.733–1.126]; P=.38), but modified overall response (mOR) was higher with Ven+Aza vs Pbo+Aza (76.2% vs 57.7%; nominal P<.0001; Garcia-Manero SOHO 2025). Here, we present additional outcomes and pre-planned subgroup analyses from VERONA with the aim of identifying patient subsets that may have received clinical benefit from Ven+Aza. Methods: VERONA enrolled patients aged ≥18 years with a diagnosis of MDS (WHO 2016), Revised International Prognostic Scoring System (IPSS-R) score >3 (intermediate, high, very high), ECOG PS 0–2, not immediately SCT eligible, and had no prior MDS therapy and no therapy-related MDS. Patients were randomized 1:1 to receive oral Ven 400 mg or Pbo once daily on Days 1–14 combined with IV or SC Aza 75 mg/m2 for 7 days in each 28-day cycle. Primary endpoint was OS. Patients were stratified by IPSS-R risk (very high, high, intermediate), region (North America, Europe, Japan, China, rest of world), and HCT eligibility. Pre-planned subgroup analyses were conduct...