The evolution of targeted therapy in pediatric AML: gemtuzumab ozogamicin, FLT3/IDH/BCL2 inhibitors, and other therapies

Despite the maximum intensification of chemotherapy and the increased use of hematopoietic stem cell transplantation (HCT) in pedi at ric patients with acute mye loid leu ke mia (AML), nearly 40 % of patients still expe ri ence relapse, and cure in this set ting remains a sig nifi cant chal lenge. Recent improve ments in AML char ac ter iza tion, includ ing advances in fl ow cytom e try and com pre hen sive geno mic sequenc ing, have led to a bet ter under stand ing of AML biol ogy and the iden-ti fi ca tion of mul ti ple poten tial ther a peu tic tar gets. Novel agents targeting geno mic lesions, cell sur face anti gens, and other mech a nisms that per mit onco gen e sis or immune escape are being incor po rated into cur rent treat ment strat e gies or are under inves ti ga tion in efforts to improve out comes and decrease the toxicities and late effects asso ci ated with tra-ditional intensive chemotherapeutic and HCT treatment. However, multiple challenges still exist, including the biologic and immunophenotypic het ero ge ne ity of child hood AML, the dif fer ences in under ly ing biol ogy as com pared to adult AML, and the significant potential for on-target/off-tumor toxicity associated with therapies directed at targets com-mon to mye loid cells, both leu ke mic and nor mal. This arti cle reviews the cur rent land scape of genomic and cell sur face tar gets for chil dren with AML with a focus on the cur rently avail able targeted ther a peu tic agents, those in active clin i cal investigation, and those still in development.

Automated summary

Despite advances in treatment for pediatric AML, there are still many challenges to overcome. Recent research focuses on discovering and developing new therapeutic targets to improve patient outcomes. This article reviews the current landscape of genomic and cell surface targets for children with AML, including available therapeutic agents, ongoing clinical trials, and drugs still in development.