Work

Venetoclax plus pediatric regimen in adolescents and adults with Ph-negative acute lymphoblastic leukemia

Year: 2026

Type: article

Abstract: ABSTRACT: The B-cell lymphoma 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 end point 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 end point. 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 with that of the historical cohort. These results demonstrate that adding venetoclax to pediatric-inspired chemotherapy significantly improves MRD response and survival outcomes in newly diagnosed (ND) Ph- ALL, with a manageable safety profile. This trial was registered at www.clinicaltrials.gov as #NCT05660473.

Source: Blood

DOI: 10.1182/blood.2026033577