Go online to PeerView.com/RMG860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Innovative intensive therapy, often consisting of potent induction/consolidation protocols followed by hematopoietic stem cell transplant (HCT), has been shown to extend survival in challenging acute myeloid leukemia (AML) settings where conventional chemotherapy options are suboptimal. In this “Clinical Consults” activity, a panel of experts provide guidance on the optimized selection of intensive upfront therapy in challenging AML subtypes and discuss how the personalized use of induction/consolidation platforms can create opportunities for subsequent HCT and lead to enhanced patient outcomes. The panelists use serial case vignettes inspired by real-world scenarios, debate the selection and use of novel cytotoxic platforms and targeted agents, and examine emerging approaches in a range of difficult-to-treat patient populations. Upon completion of this activity, participants should be better able to: Review the diagnostic, prognostic, and therapeutic implications of baseline factors such as age, genetic/molecular features, and functional status for challenging AML subtypes such as secondary AML or mutation-defined disease; Review updated clinical data surrounding novel upfront induction/consolidation regimens in diverse AML settings, including for patients with higher-risk or mutation-defined disease; Select evidence-based, personalized upfront treatment platforms for patients with challenging AML subtypes, including patients eligible for HCT; andDevelop a management plan for the unique safety considerations associated with novel upfront treatment platforms, including innovative cytotoxic and targeted regimens