Multicenter phase 2 trial of venetoclax plus azacitidine for relapsed or refractory T-cell acute lymphoblastic leukemia

Patients with relapsed or refractory T-cell acute lymphoblastic leukemia (R/R T-ALL) have limited responses to conventional chemotherapy and have poor prognosis. T-cell precursors exhibit high expression of BCL-2 and are sensitive to BCL-2 inhibitors. A multicenter phase 2 trial in China evaluated the combination of venetoclax plus azacitidine for R/R T-ALL. The primary endpoint was overall response rate. The trial included 25 patients (median age 39.0 years; IQR 27.5-56.5; 72% males) with a median duration of follow-up 31.8 months (IQR 16.2-39.3). The overall response rate was 76%: 36% complete remission; 16% complete remission with partial hematologic recovery; 16% complete remission with incomplete hematologic recovery; and 8% morphological leukemia-free state. The most common grade 3 or worse hematological adverse events were neutropenia (84%), anemia (44%), febrile neutropenia (40%), and thrombocytopenia (20%), followed by infections (12%). No treatment-related deaths occurred. The authors conclude that the venetoclax plus azacitidine regimen had a manageable safety profile and promising activity as salvage therapy for R/R T-ALL.