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The development of mutation\u2010targeted therapies has greatly enhanced the treatment armamentarium, with FLT3 inhibitors and isocitrate dehydrogenase inhibitors improving outcomes in frontline and relapsed\/refractory (RR) AML, and menin inhibitors showing efficacy in RR <jats:italic>NPM1<\/jats:italic><jats:sup>mut<\/jats:sup> and <jats:italic>KMT2A<\/jats:italic>\u2010rearranged AML. With so many new drugs approved, the number of potential combinatorial approaches to leverage the maximal benefit of these agents has increased dramatically, while at the same time introducing clinical challenges, such as key preclinical and clinical data supporting the development of combinatorial therapy, how to optimally combine or sequence these novel agents, how to optimise dose and duration to maintain safety while enhancing efficacy, the optimal duration of therapy and the role of measurable residual disease in decision\u2010making in both intensive and low\u2010intensity therapy settings. In this review, we will outline the evidence leading to the approval of key agents in AML, their on\u2010label current approvals and how they may be optimally combined in a safe and deliverable fashion to further improve outcomes in AML.<\/jats:p>","DOI":"10.1111\/bjh.19519","type":"journal-article","created":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T22:19:14Z","timestamp":1715293154000},"page":"30-47","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Combination therapy with novel agents for acute myeloid leukaemia: Insights into treatment of a heterogenous disease"],"prefix":"10.1111","volume":"205","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9339-3362","authenticated-orcid":false,"given":"Wei\u2010Ying","family":"Jen","sequence":"first","affiliation":[{"name":"Department of Leukemia The University of Texas MD Anderson Cancer Center  Houston Texas 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