New era of targeted therapy for pediatric acute lymphoblastic leukemia

Abstract

Targeted therapies has attracted attention as next-generation treatment strategies for pediatric acute lymphoblastic leukemia (ALL). One of such approach is molecular-targeted therapy, which directly inhibits aberrant molecules derived from genomic alterations that underlie leukemogenesis. For example, the introduction of tyrosine kinase inhibitors (TKIs) has markedly improved the outcomes in Philadelphia chromosome-positive ALL (Ph+ALL), and their application has recently been extended to Ph-like ALL. Additionally, menin inhibitors for KMT2A-rearranged ALL and ALK inhibitors for hematological malignancies harboring ALK fusion genes have been promising. As comprehensive genomic profiling has become increasingly integrated into clinical practice and drug development continues to advance, the selection of appropriate targeted agents may expand. Immunotherapeutic strategies targeting surface antigens have been used to treat relapsed or refractory ALL. Chimeric antigen receptor T-cells and antibody-drug conjugates reshape the therapeutic landscape. Furthermore, the bispecific T-cell engager blinatumomab has demonstrated efficacy in relapsed or refractory disease and is being evaluated in clinical trials for use in frontline treatment. In Ph+ALL, strategies incorporating TKIs and immunotherapies, such as blinatumomab, may offer an alternative to conventional chemotherapy. Although challenges remain, including the identification of risk stratification factors in targeted therapy and elucidation of the tumor immune microenvironment, the continued integration of these approaches may drive substantial progress in the treatment of pediatric ALL.