A new clinical study published inBloodwas led by Prof. Jianxiang Wang, Hui Wei, and YingchangMi from the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College. The results demonstrated that venetoclax combined with pediatric-inspired chemotherapy yields significant efficacy in newly diagnosed adolescent and adult patients with Philadelphia-negative acute lymphoblastic leukemia (Ph-negative ALL). It is the first large-scale prospective cohort study of its kind. These findings provide important evidence for optimizing current treatment strategies for Ph-negative ALL.

Acute lymphoblastic leukemia (ALL) is a highly aggressive hematologic malignancy. Although breakthrough has been made in the treatment of pediatric patients over the past few decades, outcomes for adolescent and adult patients remain suboptimal. In recent years, pediatric-inspired chemotherapy regimens have become the standard care for adolescents and adults with ALL, demonstrating significantly better efficacy than traditional adult regimens. However, a key challenge persists: among patients who achieve complete remission (CR) after induction chemotherapy, approximately 50% still have detectable measurable residual disease (MRD), and persistent MRD positivity is the strongest predictor of disease relapse. Therefore, how to further improve thedepth remission,increase the rate of MRD negativity, and thereby reduce the risk of relapse and prolong survival has become an urgent need in the field of adult ALL research.

This phase 2, single-arm trial enrolled 167 patients aged 14-60 years with newly diagnosed Ph-negativeALL. All participants received venetoclax in combination with a pediatric-inspired chemotherapy backbone (modified from the IH-2014 regimen at the Leukemia Center, Institute of Hematology & Blood Diseases Hospital).TheCRrate was 91.0%, and among responders, 73.0% achieved MRDnegativity by flow cytometry after induction. This represents a substantial improvement over historicalcontrols.Notably, the regimen also showed promising activity in the high-risk early T-cell precursor ALL (ETP-ALL) subset, which is typically refractory to conventional chemotherapy. After a median follow-up of 19.3 months, median overall survival (OS) and disease-free survival (DFS) had not yet been reached, with estimated 2-year OS and DFS rates of 78.5% and 76.7%, respectively. A propensityscore-matched comparison with the IH-2014 historical cohort confirmed a significant survival advantage with the venetoclax-containing regimen, observed in both B-cell ALL and T -cell ALL subgroups. Regarding safety, grade ≥3 adverse events were predominantly hematologic toxicities and infections, with incidences similar to those of the historical control group, indicating that the combination offers substantial efficacy without adding unmanageable toxicity. Overall, this study provides prospective evidence supporting BCL-2 inhibition as a frontline strategy in Ph-negative ALL and offers important guidance for optimizing current treatment paradigms.

This study was supported by National Key Research and Development Program of China (2023YFC2508900),National Natural Science Foundation of China (82370183, 82341213), CAMS Innovation Fund for Medical Sciences (2024-I2M-ZH-015, 2025-I2M-XHZY-033), Tianjin Natural Science Foundation Project (23JCZXJC00310), Tianjin Municipal Science and Technology Commission Grant (25ZXRKSY00050).Professor Jianxiang Wang, Chief Physician Hui Wei, and Chief Physician Yingchang Mi from the Institute of Hematology & Blood Diseases Hospital served as co-corresponding authors, and Associate Chief Physician Xiaoyuan Gong was the first author.

Link: https://ashpublications.org/blood/article/doi/10.1182/blood.2026033577/568615/Venetoclax-Plus-Pediatric-Regimen-in-Adolescents