Why Is Progress in Acute Myeloid Leukemia So Slow?

Therapeutic progress in acute myeloid leukemia (AML) is generally acknowledged to have been slower than that in the other commonly occurring types of leukemia. To a very large extent this reflects a relative lack of understanding of AML “biology” and in particular an inability to identify genetic and/or molecular aberrations not found in normal myeloid precursors (“targets”). Here, however, I also point out that the pace of development/acceptance of new therapies may be retarded by continued adherence to past practices, although these may lack empirical support. Among these practices are reliance on preclinical models that do not accurately represent clinical AML, delay in combining targeted therapies with each other or with “chemotherapy,” and limitation of eligibility for clinical trials to patients with relapsed/refractory AML or unfit patients with newly diagnosed disease, and the stereotyped use of single-arm phase II trials followed by very large randomized phase III trials. Finally, I question whether improvement in survival should be the sole or even principal criterion for approval of new drugs in AML.