Venetoclax and decitabine vs intensive chemotherapy as induction for young patients with newly diagnosed AML
Abstract
Abstract Venetoclax (VEN) combined with hypomethylating agents is approved for frontline therapy in older/unfit patients with acute myeloid leukemia (AML). However, prospective data on this low-intensity therapy in treatment-naive younger patients with AML are lacking. This study investigated the efficacy and safety of VEN plus decitabine (VEN-DEC) as induction in untreated young fit patients with AML in a randomized trial. Patients aged 18 to 59 years eligible for intensive chemotherapy were randomized 1:1 to receive VEN-DEC or IA-12 (idarubicin and cytarabine). All patients achieved composite complete remission (CRc) underwent high-dose cytarabine consolidation. The primary end point was CRc rate after induction. Of 255 screened, 188 were enrolled and randomly assigned, with 94 in each group. In the intention-to-treat population, CRc was 89% (84/94) in the VEN-DEC group vs 79% (74/94) in the IA-12 group (noninferiority P = .0021), with measurable residual disease negativity rates of 80% (67/84) vs 76% (56/74), respectively. VEN-DEC showed superior CRc in patients aged ≥40 years (91% vs 75%) and those with adverse risk (91% vs 42%) or epigenetic mutations (91% vs 67%), but lower CRc in RUNX1::RUNX1T1 fusion cases (44% vs 88%) than IA-12. Patients in the VEN-DEC group experienced fewer grade ≥3 infections (32% vs 67%) and shorter severe thrombocytopenia duration (median, 13 vs 19 days; P < .001). At a median follow-up of 12.1 months, overall and progression-free survival were similar between groups. In conclusion, VEN-DEC demonstrated noninferior response rates with superior safety over IA-12 in young patients with AML. The trial was registered at www.clinicaltrials.gov as #NCT05177731.
Article Details
Authors (22)
Jing Lu
Sheng-li Xue
1Department of Hematology, The First Affiliated Hospital of Soochow University, National Clinical Research Center for Hematologic Diseases, Suzhou, China
Ying Wang
Xue-feng He
1Department of Hematology, The First Affiliated Hospital of Soochow University, National Clinical Research Center for Hematologic Diseases, Suzhou, China
Xiao-hui Hu
1Department of Hematology, The First Affiliated Hospital of Soochow University, National Clinical Research Center for Hematologic Diseases, Suzhou, China
Miao Miao
Yang Zhang
Zai-xiang Tang
4Department of Biostatistics, School of Public Health, Suzhou Medical College of Soochow University, Suzhou, China
Jun-dan Xie
1Department of Hematology, The First Affiliated Hospital of Soochow University, National Clinical Research Center for Hematologic Diseases, Suzhou, China
Xiao-fei Yang
1Department of Hematology, The First Affiliated Hospital of Soochow University, National Clinical Research Center for Hematologic Diseases, Suzhou, China
Ming-Zhu Xu
1The First Affiliated Hospital of Soochow University, Suzhou, China
Yao-yao Shen
1Department of Hematology, The First Affiliated Hospital of Soochow University, National Clinical Research Center for Hematologic Diseases, Suzhou, China
Feng Du
Qian Wu
Meng-xing Xue
1Department of Hematology, The First Affiliated Hospital of Soochow University, National Clinical Research Center for Hematologic Diseases, Suzhou, China
Yun Wang
Ai-ling Deng
1Department of Hematology, The First Affiliated Hospital of Soochow University, National Clinical Research Center for Hematologic Diseases, Suzhou, China
Xue-qing Dou
1Department of Hematology, The First Affiliated Hospital of Soochow University, National Clinical Research Center for Hematologic Diseases, Suzhou, China
Yang Xu
Hai-ping Dai
1Department of Hematology, The First Affiliated Hospital of Soochow University, National Clinical Research Center for Hematologic Diseases, Suzhou, China
De-pei Wu
1Department of Hematology, The First Affiliated Hospital of Soochow University, National Clinical Research Center for Hematologic Diseases, Suzhou, China
Su-ning Chen
1Department of Hematology, The First Affiliated Hospital of Soochow University, National Clinical Research Center for Hematologic Diseases, Suzhou, China