Venetoclax Plus Blinatumoma as First Line Therapy for Newly Diagnosed Ph-Negative B-Cell Acute Lymphoblastic Leukemia

Purpose: This study evaluated the efficacy and safety of a 14-day blinatumomab-venetoclax (BV) regimen as induction therapy for newly diagnosed Ph-negative B-cell acute lymphoblastic leukemia (B-ALL), focusing on rapid remission and tolerability in unfit patients. Patients and Methods: Thirteen patients received venetoclax (100 mg on day 1, 200 mg on day 2, 300 mg on day 3, and 400 mg from days 4 to 14) with blinatumomab (9 to 28 ug/day) for 14 days. Bone marrow assessments were performed at days 14-21. Primary endpoints were complete remission (CR) rate, minimal residual disease (MRD) negativity by flow cytometry, and adverse events. Results: The CR rate after one cycle of BV regimen was 92.3% (12/13), and all patients achieved MRD-negativity; 91.7% (11/12) achieved MRD clearance by day 21. Grade 1-2 cytokine release syndrome occurred in 46.2% (6/13; 1 grade 3). Hematologic toxicity included grade 3-4 neutropenia (92.3%) and thrombocytopenia (46.2%), with only 30.8% febrile neutropenia. All AEs resolved rapidly with supportive care, allowing therapy to continue without interruption. At median follow-up of 283 days, 1-year relapse-free survival rate and overall survival rate were 60.6% and 83.3%. Conclusion: The 14-day BV regimen induced rapid deep remission (91.7% MRD-negative by day 21) with manageable toxicity in Ph-negative B-ALL. Synergistic T-cell activation by venetoclax may explain enhanced efficacy.