What are the most promising new agents in acute myeloid leukemia?

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Abstract

Purpose of review

Although the treatment paradigm for acute myeloid leukemia (AML) had been largely unchanged for many years, in-depth molecular characterization has revolutionized our understanding of mutations that drive the disease, subsequently serving to guide current clinical investigation. Furthermore, recent advances in the field have highlighted the importance of optimizing known efficacious agents by improving drug delivery or bypassing resistance mechanisms. The current status of novel agents which are shaping the clinical management of AML patients are summarized in this review.

Recent findings

Practice changing findings over the past year include improved overall survival (OS) in a molecularly defined AML subgroup as well as in elderly patients with secondary AML (sAML). Specifically, synergistic combination of daunorubicin and cytarabine (i.e., CPX-351) was found to improve OS in sAML patients. Furthermore, although multiple mutation specific inhibitors have been developed, optimal combination with additional agents appears critical, as monotherapies have not resulted in durable remissions or improved outcomes. Improved OS via the addition of midostaurin to intensive chemotherapy in FLT3 mutant AML supports this concept.

Summary

For the first time in AML, personalized therapy has become possible through improved understanding of the molecular architecture and survival pathways of an individual's disease. The landscape of AML treatment is encouraging, with multiple novel agents likely to gain approval over the next 5 years.

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