Evolving Role of Targeted Therapies in Acute Lymphoblastic Leukemia: ASystematic Review and Meta-Analysis

Background: Acute lymphoblastic leukemia (ALL) constitutes a substantial portion of pediatric and adult cancers, with high-risk cases posing significant challenges despite advancements in treatment. Targeted therapies offer a promising approach by addressing specific molecular pathways implicated in leukemogenesis. Objective: This study aims to perform a systematic literature review and meta-analysis to evaluate the efficacy and safety of treatments, considering the evolving nature of targeted therapies for ALL. Methods: A systematic search of PubMed, Embase, and the Cochrane Central Register of Controlled Trials was conducted up to January 2024. Phase II-III randomized controlled trials comparing targeted therapies alongside standard chemotherapy versus chemotherapy alone in ALL patients were eligible. Primary outcomes included complete remission, event-free survival, and overall survival, with secondary outcomes focusing on adverse events. Data extraction and bias assessment were performed independently by two authors. Random-effects meta-analyses were employed to determine pooled risk ratios or hazard ratios, with heterogeneity assessed using I^2 statistics. Results: Fifteen studies were included, evaluating various targeted therapies such as tyrosine kinase inhibitors, monoclonal antibodies, histone deacetylase inhibitors, phosphoinositide 3-kinase/AKT/m-TOR inhibitors. Meta-analysis revealed significantly higher rates of complete remission with targeted therapies (RR 1.11, 95% CI 1.03 to 1.19). While trends towards improved event-free survival (HR 0.87, 95% CI 0.75 to 1.01) and overall survival (HR 0.89, 95% CI 0.78 to 1.01) were observed, they did not reach statistical significance. Targeted therapies were associated with increased rates of febrile neutropenia. Conclusion: Combining targeted therapies with chemotherapy significantly enhances complete remission rates and shows promising trends in event-free survival. However, further investigation is required to optimize targeted agents and establish their definitive impact on overall survival.