The combination therapy with venetoclax in therapeutic strategy of acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) is characterized by the malignant transformation and proliferation of lymphoid progenitor cells in the bone marrow, blood, and extramedullary sites. Leukemic cells can develop drug resistance both before and after treatment, complicating disease management. Combination therapy with Venetoclax has been shown to enhance the efficacy of standard anti-leukemia drugs. Therefore, this study aims to review combination treatment strategies as potential therapeutic alternatives, drawing on evidence from previous published literature. This narrative review summarizes and critically discusses published preclinical and clinical studies evaluating Venetoclax-based combination therapies in ALL, with an emphasis on mechanistic rationale and therapeutic implications. Available evidence indicates that combinations of Venetoclax with hypomethylating agents, monoclonal antibodies, kinase inhibitors, and cytotoxic chemotherapies may enhance apoptotic signaling and improve antileukemic activity across multiple ALL subtypes, including high-risk and heavily pretreated populations. Venetoclax-based combination strategies represent a promising and flexible therapeutic approach in ALL. However, current evidence is largely derived from heterogeneous and non-randomized studies, underscoring the need for well-designed prospective trials to define optimal regimens and patient selection.