Targeting tomorrow: Evaluation of novel agents for infants with KMT2A-rearranged acute lymphoblastic leukaemia

Infants with KMT2A-rearranged (KMT2A-r) acute lymphoblastic leukaemia (ALL) have a historically poor prognosis with high rates of relapse. Further treatment intensification with conventional chemotherapy is precluded by dose-limiting toxicities. Extensive preclinical evaluation has been performed to identify novel therapies to improve outcome for infants with KMT2A-r ALL. However, there is considerable heterogeneity regarding the extent of experimental research conducted and combined with the increasing volume of preclinical studies, presents a barrier to selecting the best agents for translation into clinical trials. In addition, the relative rarity of infant ALL limits the number of novel therapies that can be clinically evaluated at any one time. In this systematic review, we detail the preclinical studies of novel agents performed for KMT2A-r infant ALL and highlight areas for further investigation, providing the basis to enhance future preclinical research and integrate novel agents into clinical practice to improve outcomes for infants with KMT2A-r ALL.