Shaping the AML Treatment Landscape—Modeling a Path through Plenty, Uncertainty, and Paucity

The last two decades have identified and characterized heterogeneities arising in the genetic structure of the bone marrow malignancy, acute myeloid leukemia (AML), to partly explain the variation in outcomes among similarly treated patients.1 In high-income countries, treatment paradigms for AML have now shifted to include conventional chemotherapy and/or small molecule drugs directed against biological targets, deemed disease-defining.1 2 3 Apart from the acute promyelocytic leukemia variant,4 however, AML remains incurable for a significant number of patients within different disease subgroups. In addition, the incremental survival gain with small molecule drugs is relatively modest,2 3 5 and the costs associated with therapy, supportive care, and disease-monitoring remain considerable. In low-and middle-income countries, financial constraints often render therapies, considered "standard-of-care" in higher income countries, prohibitively expensive.6 Increasingly, the rarity of biological subtypes of AML1 and the availability of multiple drugs targeting unique disease sub-types2 5 7 8 are also beginning to present challenges to the design of contemporaneous clinical trials. To optimize clinical benefits and the cost-effectiveness of therapy to patients and healthcare systems, as well as to address key clinical hypotheses, an innovative approach for hypothesis testing and identifying best therapy is, therefore, required.