Venetoclax Plus Pediatric Regimen in Adolescents and Adults with Ph-Negative Acute Lymphoblastic Leukemia
Abstract
The BCL-2 inhibitor venetoclax has shown promise in acute lymphoblastic leukemia (ALL), but its role in first-line therapy for newly diagnosed (ND) Philadelphia chromosome-negative (Ph⁻) ALL is undefined. In this prospective phase 2 study, 167 adolescents and adults (aged 14-60 years) with ND Ph⁻ ALL received venetoclax combined with pediatric-inspired chemotherapy. The primary endpoint was the rate of measurable residual disease (MRD) negativity by multiparameter flow cytometry (MFC) after induction. The complete remission rate was 91.0%, and 73.0% of responders achieved MFC-MRD negativity, meeting the primary endpoint. After a median follow-up of 19.3 months, median overall and disease-free survival were not reached; estimated 2-year survival rates were 78.5% and 76.7%, respectively. Propensity score-matched analysis confirmed superior survival compared with historical chemotherapy-only controls. Grade ≥ 3 adverse events were primarily hematologic toxicities and infections, with an incidence comparable to that of the historical cohort. These results demonstrate that adding venetoclax to pediatric-inspired chemotherapy significantly improves MRD response and survival outcomes in ND Ph⁻ ALL, with a manageable safety profile. This trial was registered with ClinicalTrials.gov under the identifier NCT05660473.
Article Details
Authors (18)
Xiaoyuan Gong
Leukemia center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, Tianjin, China
Yuntao Liu
Qiuyun Fang
Leukemia center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, Tianjin, China
Runxia Gu
Leukemia center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, Tianjin, China
Kaiqi Liu
Dong Lin
Chunlin Zhou
Guangji Zhang
Benfa Gong
Leukemia center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, Tianjin, China
Shuning Wei
Leukemia center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, Tianjin, China
Yan Li
Shouyun Li
1. State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chine, tianjin, China
Shaowei Qiu
1. State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China; 2. Tianjin Institutes of Health Science, Tianjin 301600, China., Tianjin, China
Bingcheng Liu
Ying Wang
Yingchang Mi
Hui Wei
Jianxiang Wang